Fortilin Interacts with TGF-β1 and Prevents TGF-β Receptor Activation

Fortilin is a 172-amino acid multifunctional protein present in both intra- and extracellular spaces. Although fortilin binds and regulates various cellular proteins, the biological role of extracellular fortilin remains unknown. Here we report that fortilin specifically interacts with TGF-β1 and prevents it from activating the TGF-β1 signaling pathway. In a standard immunoprecipitation-western blot assay, fortilin co-immunoprecipitates TGF-β1 and its isoforms. The modified ELISA assay shows that TGF-β1 remains complexed with fortilin in human serum. Both bio-layer interferometry and surface plasmon resonance (SPR) reveal that fortilin directly bind TGF-β1. The SPR analysis also reveals that fortilin and the TGF-β receptor II (TGFβRII) compete for TGF-β1. Both luciferase and secreted alkaline phosphatase reporter assays show that fortilin prevents TGF-β1 from activating Smad3 binding to Smad-binding element. Fortilin inhibits the phosphorylation of Smad3 in both quantitative western blot assays and ELISA. Finally, fortilin inhibits TGFβ-1-induced differentiation of C3H10T1/2 mesenchymal progenitor cells to smooth muscle cells. A computer-assisted virtual docking reveals that fortilin occupies the pocket of TGF-β1 that is normally occupied by TGFβRII and that TGF-β1 can bind either fortilin or TGFβRII at any given time. These data support the role of extracellular fortilin as a negative regulator of the TGF-β1 signaling pathway

What Makes a Better Smeller?

Olfaction is often viewed as difficult, yet the empirical evidence suggests a different picture. A closer look shows people around the world differ in their ability to detect, discriminate, and name odors. This gives rise to the question of what influences our ability to smell. Instead of focusing on olfactory deficiencies, this review presents a positive perspective by focusing on factors that make someone a better smeller. We consider three driving forces in improving olfactory ability: one's biological makeup, one's experience, and the environment. For each factor, we consider aspects proposed to improve odor perception and critically examine the evidence; as well as introducing lesser discussed areas. In terms of biology, there are cases of neurodiversity, such as olfactory synesthesia, that serve to enhance olfactory ability. Our lifetime experience, be it typical development or unique training experience, can also modify the trajectory of olfaction. Finally, our odor environment, in terms of ambient odor or culinary traditions, can influence odor perception too. Rather than highlighting the weaknesses of olfaction, we emphasize routes to harnessing our olfactory potential

A preliminary study on the effects of star fruit consumption on antioxidant and lipid status in elderly Thai individuals

Jirakrit Leelarungrayub,1 Araya Yankai,1 Decha Pinkaew,1 Rungthip Puntumetakul,2 James J Laskin,3 Richard J Bloomer4 1Department of Physical Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 2Research Center in Back, Neck, Other Joint Pain and Human Performance (BNOJPH), Khon Kaen University, Khon Kaen, Thailand; 3School of Physical Therapy and Rehabilitation Sciences, University of Montana, Missoula, MT, 4Cardiorespiratory/Metabolic Laboratory, School of Health Studies, University of Memphis, Memphis, TN, USA Objective: The aims of this preliminary study were to evaluate the antioxidant and lipid status before and after star fruit juice consumption in healthy elderly subjects, and the vitamins in star fruit extracts.Methods: A preliminary designated protocol was performed in 27 elderly individuals with a mean (±SD) age of 69.5±5.3 years, by planning a 2-week control period before 4 weeks of consumption of star fruit twice daily. Oxidative stress parameters such as total antioxidant capacity, glutathione, malondialdehyde, protein hydroperoxide, multivitamins such as L-ascorbic acid (Vit C), retinoic acid (Vit A), and tocopherol (Vit E), and the lipid profile parameters such as cholesterol, triglyceride, high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) were analyzed. Moreover, Vit C, Vit A, and Vit E levels were evaluated in the star fruit extracts during the 4-week period.Results: In the 2-week control period, all parameters showed no statistically significant difference; after 4 weeks of consumption, significant improvement in the antioxidant status was observed with increased total antioxidant capacity and reduced malondialdehyde and protein hydroperoxide levels, as well as significantly increased levels of Vit C and Vit A, when compared to the two-time evaluation during the baseline periods. However, glutathione and Vit E showed no statistical difference. In addition, the HDL-C level was higher and the LDL-C level was significantly lower when compared to both baseline periods. But the levels of triglyceride and cholesterol showed no difference. Vit C and Vit A were identified in small quantities in the star fruit extract.Conclusion: This preliminary study suggested that consumption of star fruit juice twice daily for 1 month improved the elderly people’s antioxidant status and vitamins, as well as improved the lipoproteins related to Vit C and Vit A in the star fruit extract. Keywords: star fruit, elderly, antioxidants, vitamins, lipid, oxidative stres

Who shapes the politics of expertise? Co-production and authoritative knowledge in Thailand’s political forests

Expert environmental knowledge has often been described as a governmental rationality that reduces political debate and facilitates state control. In this paper, I argue instead that this line of reasoning simplifies how knowledge gains political authority, especially when expertise is shared and left unchallenged by diverse actors, including those in conflict with each other. Using the framework of co-production from Science and Technology Studies (STS), I apply this argument to conflicts over the supposed watershed functions of forests in Thailand, where simplified narratives about the impacts of land use on water supply are used as justifications for territorialisation and restrictions on forest land. In particular, I focus on local resistance to the proposed Kaeng Sua Ten dam in northern Thailand in order to demonstrate how protestors have deliberately reproduced formal expertise to empower themselves, but by so doing also reinforcing simplified visions of watershed science and community culture. I argue that exposing the co-production of authoritative knowledge and visions of social order offer greater opportunities for understanding the role of expertise as a political force than analysing competing assemblages based on oppositions of state-led expert knowledge and traditional local practices