The role of glial cells in regulation of neurotransmitter amino acids in the external environment. II. Mechanism of aspartate transport

Background: RADA-4 (Ac-RADARADARADARADA-NH2) is the most extensively studied and marketed self-assembling peptide, forming hydrogel, used to create defined threedimensional microenvironments for cell culture applications. Objectives: In this work, we use various biophysical techniques to investigate the length dependency of RADA aggregation and assembly. Methods: We synthesized a series of RADA-N peptides, N ranging from 1 to 4, resulting in four peptides having 4, 8, 12, and 16 amino acids in their sequence. Through a combination of various biophysical methods including thioflavin T fluorescence assay, static right angle light scattering assay, Dynamic Light Scattering (DLS), electron microscopy, CD, and IR spectroscopy, we have examined the role of chain-length on the self-assembly of RADA peptide. Results: Our observations show that the aggregation of ionic, charge-complementary RADA motifcontaining peptides is length-dependent, with N less than 3 are not forming spontaneous selfassemblies. Conclusion: The six biophysical experiments discussed in this paper validate the significance of chain-length on the epitaxial growth of RADA peptide self-assembly.

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10 THE ROLE OF DIETARY L-SERINE IN THE REGULATION OF INTESTINAL MUCUS BARRIER DURING INFLAMMATION

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.110 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S42-S42

Author(s):

Kohei Sugihara ◽

Nobuhiko Kamada

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Gut Microbiota ◽

Control Diet ◽

Bacterial Strains ◽

Germ Free ◽

Intestinal Mucus ◽

Gnotobiotic Mice ◽

Mucus Barrier

Abstract Background Recent accumulating evidence suggests that amino acids have crucial roles in the maintenance of intestinal homeostasis. In inflammatory bowel disease (IBD), amino acid metabolism is changed in both host and the gut microbiota. Among amino acids, L-serine plays a central role in several metabolic processes that are essential for the growth and survival of both mammalian and bacterial cells. However, the role of L-serine in intestinal homeostasis and IBD remains incompletely understood. In this study, we investigated the effect of dietary L-serine on intestinal inflammation in a murine model of colitis. Methods Specific pathogen-free (SPF) mice were fed either a control diet (amino acid-based diet) or an L-serine-deficient diet (SDD). Colitis was induced by the treatment of dextran sodium sulfate (DSS). The gut microbiome was analyzed by 16S rRNA sequencing. We also evaluate the effect of dietary L-serine in germ-free mice and gnotobiotic mice that were colonized by a consortium of non-mucolytic bacterial strains or the consortium plus mucolytic bacterial strains. Results We found that the SDD exacerbated experimental colitis in SPF mice. However, the severity of colitis in SDD-fed mice was comparable to control diet-fed mice in germ-free condition, suggesting that the gut microbiota is required for exacerbation of colitis caused by the restriction of dietary L-serine. The gut microbiome analysis revealed that dietary L-serine restriction fosters the blooms of a mucus-degrading bacterium Akkermansia muciniphila and adherent-invasive Escherichia coli in the inflamed gut. Consistent with the expansion of mucolytic bacteria, SDD-fed mice showed a loss of the intestinal mucus layer. Dysfunction of the mucus barrier resulted in increased intestinal permeability, thereby leading to bacterial translocation to the intestinal mucosa, which subsequently increased the severity of colitis. The increased intestinal permeability and subsequent bacterial translocation were observed in SDD-fed gnotobiotic mice that colonized by mucolytic bacteria. In contrast, dietary L-serine restriction did not alter intestinal barrier integrity in gnotobiotic mice that colonized only by non-mucolytic bacteria. Conclusion Our results suggest that dietary L-serine regulates the integrity of the intestinal mucus barrier during inflammation by limiting the expansion of mucus degrading bacteria.

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Hegemonic Distortions: The Securitisation of the Insurgency in Thailand's Deep South

TRaNS Trans -Regional and -National Studies of Southeast Asia ◽

10.1017/trn.2018.13 ◽

2019 ◽

Vol 7 (2) ◽

pp. 209-232

Author(s):

Nicole Jenne ◽

Jun Yan Chang

Keyword(s):

External Environment ◽

Southeast Asian ◽

Deep South ◽

Internal Security ◽

Current Period ◽

Security Challenges ◽

Islamist Terrorism ◽

Political Decisions

AbstractThe conflict between the Thai state and the Malay-Muslim insurgency in the country's Deep South is one of Southeast Asia's most persistent internal security challenges. The start of the current period of violence dates back to the early 2000s, and since then, a significant number of studies exploring the renewed escalation have been published. In this study, we argue that existing scholarship has not adequately accounted for the external environment in which political decisions were taken on how to deal with the southern insurgency. We seek to show how the internationally dominant, hegemonic security agenda of so-called non-traditional security (NTS) influenced the Thai government's approach to the conflict. Building upon the Copenhagen School's securitisation theory, we show how the insurgency became securitised under the dominant NTS narrative, leading to the adoption of harsh measures and alienating discourses that triggered the escalation of violence that continues today. The specific NTS frameworks that ‘distorted’ the Thai state's approach of one that had been informed solely by local facts and conditions were those of anti-narcotics and Islamist terrorism, albeit in different ways. Based on the findings from the case study, the article concludes with a reflection on the role of the hegemonic NTS agenda and its implications for Southeast Asian politics and scholarship.

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