Nigrostriatal 6-hydroxydopamine lesions increase alpha-synuclein levels and permeability in rat colon

Increasing evidence suggests that the gut-brain axis plays a crucial role in Parkinson's disease (PD). The abnormal accumulation of aggregated alpha-synuclein (aSyn) in the brain is a key pathological feature of PD. Intracerebral 6-hydroxydopamine (6-OHDA) is a widely used dopaminergic lesion model of PD. It exerts no aSyn pathology in the brain, but changes in the gut have not been assessed. Here, 6-OHDA was administered unilaterally either to the rat medial forebrain bundle (MFB) or striatum. Increased levels of glial fibrillary acidic protein in the ileum and colon were detected at 5 weeks postlesion. 6-OHDA decreased the Zonula occludens protein 1 barrier integrity score, suggesting increased colonic permeability. The total aSyn and Ser129 phosphorylated aSyn levels were elevated in the colon after the MFB lesion. Both lesions generally increased the total aSyn, pS129 aSyn, and ionized calcium-binding adapter molecule 1 (Iba1) levels in the lesioned striatum. In conclusion, 6-OHDA-induced nigrostriatal dopaminergic damage leads to increased aSyn levels and glial cell activation particularly in the colon, suggesting that the gut-brain axis interactions in PD are bidirectional and the detrimental process may start in the brain

The humanistic roots of Islamic administration and leadership for education : philosophical foundations for cross-cultural and transcultural teaching

For a number of decades, a humanistic approach has been a minor but persistent one in the Western field of administrative and leadership studies, and only recently has been broadening to include other humanist traditions (Dierksmeier et al., 2011) and has yet to be fully explored in educational administration and its pedagogy and curriculum although some foundational work has been done (e.g., Samier, 2005). The focus in this chapter is on the Islamic humanist tradition as it relates to the teaching of educational administration and leadership in a Muslim context, with implications for cross-cultural and transcultural use. The second purpose of the chapter is to show the correspondences that exist between the Islamic and Western humanist traditions in terms of human values, knowledge and educational ideal, which in this chapter are argued to be close to the Western Idealist tradition and the German Bildung conception of education as well as the strong interpretive and hermeneutic foundations that originated in the Islamic tradition and which influenced the foundations of many relevant European schools of thought, particularly in the Enlightenment.The initial section of the chapter is a comparative examination of the central principles of the Islamic humanist tradition from the classical through to contemporary times with the Western humanist tradition as they relate to conceptions of the good, ethics, the construction of meaning and a set of higher order values predicated upon human dignity, integrity, empathy, well-being, and the public good (Goodman, 2003) covering a number of important scholars like Al Farabi, al Isfanhani, and Edward Said (e.g., Kraemer, 1986). In both, professions are viewed as meaningful work that allow for large measures of decision making, and are grounded in human qualities and needs including autonomy, freedom and emancipation balanced with responsibilities, obligations and duties to society. These are compared with the corresponding principles of knowledge in Western humanism which includes a strong constructivist view of reality (Makdisi, 1990). Secondly, the chapter examines the principles of good or ideal leadership and administration that humanism aims at in its preparation of officials, including those in the educational sector in both the classical Islamic tradition (Hassi, 2012) and Western approaches to humanistic administration and leadership (Czarniawska-Joerges & Guillet de Monthoux, 1994; Gagliardi & Czarniawska, 2006; Leoussi, 2000). The third section focusses on close correspondences that exist between the Islamic (Afsaruddin, 2016; al-Attas, 1980; Yasin & Jani, 2013) and Western (Aloni, 2007; Veugelers, 2011) humanist education traditions in terms of educational ideal as well as the kind of teaching practices that distinguish these traditions (Daiber, 2013; Dossett, 2014) as they apply to educational administration and leadership (Greenfield & Ribbins, 1993). The chapter concludes with a discussion of how the Islamic humanist tradition can contribute to cross-cultural and transcultural graduate teaching in international educational administration (Khan & Amann, 2013)

Measurement methodology for greenhouse gas emissions from storage of forest chips - A review

201

Comparison of Experimental Strategies to Study l-Type Amino Acid Transporter 1 (LAT1) Utilization by Ligands

l-Type amino acid transporter 1 (LAT1), expressed abundantly in the brain and placenta and overexpressed in several cancer cell types, has gained a lot of interest in drug research and development, as it can be utilized for brain-targeted drug delivery, as well as inhibiting the essential amino acid supply to cancer cells. The structure of LAT1 is today very well-known and the interactions of ligands at the binding site of LAT1 can be modeled and explained. However, less is known of LAT1′s life cycle within the cells. Moreover, the functionality of LAT1 can be measured by several different methods, which may vary between the laboratories and make the comparison of the results challenging. In the present study, the usefulness of indirect cis-inhibition methods and direct cellular uptake methods and their variations to interpret the interactions of LAT1-ligands were evaluated. Moreover, this study also highlights the importance of understanding the intracellular kinetics of LAT1-ligands, and how they can affect the regular function of LAT1 in critical tissues, such as the brain. Hence, it is discussed herein how the selected methodology influences the outcome and created knowledge of LAT1-utilizing compounds

Volatile fatty acids (VFAs) and methane from food waste and cow slurry: Comparison of biogas and VFA fermentation processes

201

Nigrostriatal 6-hydroxydopamine lesions increase alpha-synuclein levels and permeability in rat colon

Increasing evidence suggests that the gut–brain axis plays a crucial role in Parkinson’s disease (PD). The abnormal accumulation of aggregated alpha-synuclein (aSyn) in the brain is a key pathological feature of PD. Intracerebral 6-hydroxydopamine (6-OHDA) is a widely used dopaminergic lesion model of PD. It exerts no aSyn pathology in the brain, but changes in the gut have not been assessed. Here, 6-OHDA was administered unilaterally either to the rat medial forebrain bundle (MFB) or striatum. Increased levels of glial fibrillary acidic protein in the ileum and colon were detected at 5 weeks postlesion. 6-OHDA decreased the Zonula occludens protein 1 barrier integrity score, suggesting increased colonic permeability. The total aSyn and Ser129 phosphorylated aSyn levels were elevated in the colon after the MFB lesion. Both lesions generally increased the total aSyn, pS129 aSyn, and ionized calcium-binding adapter molecule 1 (Iba1) levels in the lesioned striatum. In conclusion, 6-OHDA-induced nigrostriatal dopaminergic damage leads to increased aSyn levels and glial cell activation particularly in the colon, suggesting that the gut–brain axis interactions in PD are bidirectional and the detrimental process may start in the brain.Peer reviewe

Introduction

La fonction de siège de la seigneurie donne la définition même du château et le distingue de toutes les autres formes d’habitat. S’il incarne le pouvoir militaire du seigneur depuis le Moyen Âge, le château subit une mutation importante lors de la pacification de la France au cours du xviie siècle. Bien que le seigneur demeure le représentant de l’ordre et des institutions monarchiques à l’échelle locale, la fin des guerres civiles entraîne la disparition de la dimension défensive du château...

Development and Evaluation of Two Potential 5-HT₇ Receptor PET Tracers:[¹⁸F]ENL09 and [¹⁸F]ENL10

The latest addition to the serotonin (5-HT) receptor family is the 5-HT7 receptor (5-HT7R). This receptor has gained interest as a drug target due to its involvement in various disorders such as depression or schizophrenia. There is currently no clinically validated positron emission tomography (PET) tracer for the 5-HT7R available. But, the (arylpiperazinyl-butyl)­oxindole scaffold provides a promising lead structure for this purpose. Here, we synthesized 12 (arylpiperazinyl-butyl)­oxindole derivatives and in vitro affinity screening identified two structures with suitable affinity and selectivity to be radiolabeled and tested as 5-HT7R selective PET tracers. Next, the radiolabeled products [18F]­ENL09 and [18F]­ENL10 were evaluated as PET tracers in rats. Both tracers were found to be P-gp substrates, but after P-gp inhibition the brain uptake showed a regional distribution in line with the known 5-HT7R distribution.  The [18F]­ENL10 brain binding was displaceable with a 5-HT7R selective ligand, whereas [18F]­ENL09 was not. We find that [18F]­ENL10 is a promising 5-HT7R selective PET tracer candidate that should be investigated in higher species