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Robust, Tunable Biological Oscillations from Interlinked Positive and Negative Feedback Loops
Tsai, T. Y.-C.,Choi, Y. S.,Ma, W.,Pomerening, J. R.,Tang, C.,Ferrell, J. E. American Association for the Advancement of Scienc 2008 Science Vol.321 No.5885
<P>A simple negative feedback loop of interacting genes or proteins has the potential to generate sustained oscillations. However, many biological oscillators also have a positive feedback loop, raising the question of what advantages the extra loop imparts. Through computational studies, we show that it is generally difficult to adjust a negative feedback oscillator's frequency without compromising its amplitude, whereas with positive-plus-negative feedback, one can achieve a widely tunable frequency and near-constant amplitude. This tunability makes the latter design suitable for biological rhythms like heartbeats and cell cycles that need to provide a constant output over a range of frequencies. Positive-plus-negative oscillators also appear to be more robust and easier to evolve, rationalizing why they are found in contexts where an adjustable frequency is unimportant.</P>
Tsai, C.F.,Lin, L.J.,Wang, C.H.,Tsai, C.S.,Chang, S.C.,Lee, T.T. Asian Australasian Association of Animal Productio 2022 Animal Bioscience Vol.35 No.12
Objective: A series of experiment were conducted to evaluate the effects of replacing a part of soybean meal (SBM) at 6% of broiler diets with fermented soybean meal (FSBM) obtained by single or two-stage fermentation by measuring growth performance, antioxidant activity in the jejunum and distal intestinal microflora. Methods: Soybean meal samples were prepared by single-stage fermentation using Bacillus velezensis (Bv) (FSBM<sub>B</sub>), or Lactobacillus spp. (as commercial control) (FSBM<sub>L</sub>). Additional SBM sample was prepared by two-stage fermentation using Bv and subsequently using Lactobacillus brevis ATCC 367 (Lb) (FSBM<sub>B+L</sub>). Enzyme activity, chemical composition, trichloroethanoic acid-nitrogen solubility index (TCA-NSI) and antioxidant activity were measured. Then, in an in vivo study, 320 Ross308 broilers were divided into four groups with ad libitum supply of feed and water. Four groups were fed either a corn-soybean meal diet (SBM), or one of fermented SBM diets (FSBM<sub>B+L</sub>, FSBM<sub>B</sub>, and FSBM<sub>L</sub>). Growth, serum characteristics, microflora, and the mRNA expression of selected genes were measured. Results: Compared to SBM, FSBM<sub>B+L</sub> contained lower galacto-oligosaccharide, allergic protein, and trypsin inhibitor, and higher TCA-NSI by about three times (p<0.05). Reducing power and 1,1-diphenyl-2-picrylhydrazyl free radical scavenging ability correlated positively with the TCA-NSI content in FSBM. Growth performances were not significantly different among four groups. In jejunum of 35-day-old broilers, partial replacement of SBM by FSBM<sub>B+L</sub> increased the activity of superoxide dismutase and catalase (CAT), and the FSBM<sub>B</sub> group had the highest catalase activity (p<0.05). Partial replacement of SBM by FSBM increased relative mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and peptide transporter 1 (PepT1) (p<0.05); however, FSBM<sub>B+L</sub> increased CAT mRNA level to 5 times of the control (p<0.05). Conclusion: Using Bv- and Lb-processed SBM through two-stage fermentation to partially replace 6% of diets will improve the gut's antioxidant activity under commercial breeding in broilers.
Go, Y.Y.,Kim, Y.S.,Cheon, S.,Nam, S.,Ku, K.B.,Kim, M.,Cho, N.H.,Park, H.,Alison Lee, P.Y.,Lin, Y.C.,Tsai, Y.L.,Thomas Wang, H.T.,Balasuriya, U.B.R. American Society for Investigative Pathology and t 2017 The Journal of Molecular Diagnostics Vol.19 No.6
<P>Middle East respiratory syndrome (MERS) is an emerging zoonotic viral respiratory disease that was first identified in Saudi Arabia in 2012. In 2015, the largest MERS outbreak outside of the Middle East region occurred in the Republic of Korea. The rapid nosocomial transmission of MERS-coronavirus (MERS-CoV) in Korean health care settings highlighted the importance and urgent need for a rapid and reliable on-site diagnostic assay to implement effective control and preventive measures. Here, the evaluation and validation of two newly developed reverse transcription insulated isothermal PCR (RT-iiPCR) methods targeting the ORF1a and upE genes of MERS-CoV are described. Compared with World Health Organization recommended singleplex real-time quantitative RT-PCR (RT-qPCR) assays, both RT-iiPCR assays had comparable analytical sensitivity for the detection of MERS-CoV RNA in tissue culture fluid and in sputum samples spiked with infectious virus. Furthermore, clinical evaluation was performed with sputum samples collected from subjects with acute and chronic respiratory illnesses, including patients infected with MERS-CoV. The overall agreement values between the two RT-iiPCR assays and the reference RT-qPCR assays were 98.06% (95% CI, 94.43%-100%; K = 0.96) and 99.03% (95% CI, 95.88%-100%; K = 0.99) for ORF1a and upE assays, respectively. The ORF1a and upE MERS-CoV RT-iiPCR assays coupled with a field deployable system provide a platform for a highly sensitive and specific on-site tool for diagnosis of MERS-CoV infections.</P>
Physico-chemical confinement of helical nanofilaments
Lee, S.,Kim, H.,Shin, T. J.,Tsai, E.,Richardson, J. M.,Korblova, E.,Walba, D. M.,Clark, N. A.,Lee, S. B.,Yoon, D. K. The Royal Society of Chemistry 2015 SOFT MATTER Vol.11 No.18
<P>Helical nanofilaments (HNFs) have attracted much interest because of their unique optical properties, but there have been many hurdles to overcome in using them for the practical applications due to their structural complexity. Here we demonstrate that the molecular configuration and layer conformation of a modulated HNF (HNFs<SUB>(mod)</SUB>) can be studied using a physicochemical confinement system. The layer directions affected by the chemical affinity between the mesogen and surface were drastically controlled in surface-modified nanochannels. Furthermore, an <I>in situ</I> experiment using grazing-incidence X-ray diffraction (GIXD) was carried out to investigate in detail the structural evolution through thermal transitions. The results demonstrate that the HNF<SUB>(mod)</SUB> structure can be perfectly controlled for functional HNF device applications, and a combined system with chemical and physical confinement effects will be helpful to better understand the fundamentals of soft matter.</P> <P>Graphic Abstract</P><P>Helical nanofilaments (HNFs) have attracted much interest because of their unique optical properties, but there have been many hurdles to overcome in using them for the practical applications due to their structural complexity. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c5sm00417a'> </P>
DISC1–ATF4 transcriptional repression complex: dual regulation of the cAMP-PDE4 cascade by DISC1
Soda, T,Frank, C,Ishizuka, K,Baccarella, A,Park, Y-U,Flood, Z,Park, S K,Sawa, A,Tsai, L-H Nature Publishing Group 2013 Molecular psychiatry Vol.18 No.8
<P>Disrupted-In-Schizophrenia 1 (<I>DISC1</I>), a risk factor for major mental illnesses, has been studied extensively in the context of neurodevelopment. However, the role of DISC1 in neuronal signaling, particularly in conjunction with intracellular cascades that occur in response to dopamine, a neurotransmitter implicated in numerous psychiatric disorders, remains elusive. Previous data suggest that DISC1 interacts with numerous proteins that impact neuronal function, including activating transcription factor 4 (ATF4). In this study, we identify a novel DISC1 and ATF4 binding region in the genomic locus of <I>phosphodiesterase 4D</I> (<I>PDE4D</I>), a gene implicated in psychiatric disorders. We found that the loss of function of either DISC1 or ATF4 increases <I>PDE4D9</I> transcription, and that the association of DISC1 with the <I>PDE4D9</I> locus requires ATF4. We also show that <I>PDE4D9</I> is increased by D1-type dopamine receptor dopaminergic stimulation. We demonstrate that the mechanism for this increase is due to DISC1 dissociation from the <I>PDE4D</I> locus in mouse brain. We further characterize the interaction of DISC1 with ATF4 to show that it is regulated via protein kinase A-mediated phosphorylation of DISC1 serine-58. Our results suggest that the release of DISC1-mediated transcriptional repression of <I>PDE4D9</I> acts as feedback inhibition to regulate dopaminergic signaling. Furthermore, as DISC1 loss-of-function leads to a specific increase in <I>PDE4D9</I>, <I>PDE4D9</I> itself may represent an attractive target for therapeutic approaches in psychiatric disorders.</P>
Carroll, WM,Saida, T,Kim, HJ,Kira, J,Kermode, AG,Tsai, CP,Fujihara, K,Kusunoki, S,Tanaka, M,Kim, KK,Bates, D SAGE Publications 2013 Multiple sclerosis journal: clinical and laborator Vol.19 No.10
<P>Definite diagnosis of inflammatory demyelinating disease (multiple sclerosis (MS) and neuromyelitis optica (NMO)) may require time, but early treatment offers the opportunity to maximize patient outcomes. The purpose of this report is to provide guidance to facilitate early treatment decisions for patients with inflammatory demyelinating disease, before definitive diagnosis. Neurology experts reviewed the existing literature and clinical evidence. A treatment decision pathway was developed, defining patients for whom first-line MS disease-modifying therapies (a) are unlikely to be effective, (b) may be effective but require careful monitoring and (c) are likely to provide benefit. This algorithm seeks to ensure that patients, particularly those in Asia, receive appropriate treatment early in inflammatory demyelinating disease.</P>