NGF Causes TrkA to Specifically Attract Microtubules to Lipid Rafts

Membrane protein sorting is mediated by interactions between proteins and lipids. One mechanism that contributes to sorting involves patches of lipids, termed lipid rafts, which are different from their surroundings in lipid and protein composition. Although the nerve growth factor (NGF) receptors, TrkA and p75NTR collaborate with each other at the plasma membrane to bind NGF, these two receptors are endocytosed separately and activate different cellular responses. We hypothesized that receptor localization in membrane rafts may play a role in endocytic sorting. TrkA and p75NTR both reside in detergent-resistant membranes (DRMs), yet they responded differently to a variety of conditions. The ganglioside, GM1, caused increased association of NGF, TrkA, and microtubules with DRMs, but a decrease in p75NTR. When microtubules were induced to polymerize and attach to DRMs by in vitro reactions, TrkA, but not p75NTR, was bound to microtubules in DRMs and in a detergent-resistant endosomal fraction. NGF enhanced the interaction between TrkA and microtubules in DRMs, yet tyrosine phosphorylated TrkA was entirely absent in DRMs under conditions where activated TrkA was detected in detergent-sensitive membranes and endosomes. These data indicate that TrkA and p75NTR partition into membrane rafts by different mechanisms, and that the fraction of TrkA that associates with DRMs is internalized but does not directly form signaling endosomes. Rather, by attracting microtubules to lipid rafts, TrkA may mediate other processes such as axon guidance

Confronting the Right-Thinking Bourgeoisie: Shukri, Genet, and a Poetics of Inversion / مواجهة البورجوازية المحافظة: شكري وجينيه وجماليات التبديل العكسي

[Through a comparative study of Muhammad Shukri (Choukri) and Jean Genet, this article situates Shukri as a world writer who utilizes a poetics of inversion to call socially constituted discourses of authority into question. Like Genet, this aesthetic strategy allows him to uncover the systemic and symbolic forms of violence endemic in his society. Beyond their autobiographical narratives, Shukri\u27s only published play, Al-Sa\u27ada (Happiness), is interpreted next to Genet\u27s philosophy of theater to illustrate the way in which their dramatic texts work to confront their respective audiences with their own complicity in the perpetuation of unjust social hierarchies. من خلال مقارنة بين محمد شكري وجان جينيه، تعرض هذه المقالة شكري باعتباره كاتباً عالمياً اعتمد على جماليات التبديل العكسي ليتحدي النظم الاجتماعية المتسلّطة، مثله في ذلك مثل جينيه. وقد مكّن هذا المنحى شكري من تعرية أشكال العنف الممنهجة والرمزية الطاغية في مجتمعه المغربي. إلى جانب كتاباتهما الذاتية، تحلل المقالة السعادة - المسرحية الوحيدة المنشورة لشكري - اعتماداً على فلسفة جينيه المسرحية، وذلك لإبراز دور أعمال الكاتبين المسرحية في توعية المتلقي بدرجة تواطئه في دعم النظم الاجتماعية الجائرة .

The Libyan Novel: Humans, Animals and the Poetics of Vulnerability

10.1080/13629387.2022.2087266The Journal of North African Studies2841024-102

Moroccan autobiography: The rhetorical construction of the self and the development of modern Arabic narrative in al-Maghrib al-Aqsa

The question this project addresses is why modern Moroccan narrative developed largely along the generic lines of autobiography. Or, is there a discernable relationship between indigenous precursors in the Arabic narrative tradition in the Moroccan context that led the modern narrative of the region to take the initial generic form of autobiography. While the tendency is to view the Moroccan novel as a Western import, the proposition here is to draw a line of continuity between premodern Moroccan autobiographical writing and the development of modern prose in Morocco. Through a series of close readings, the links between Ahmad Zarrūq\u27s fifteenth-century al- Kunnāsh fi \u27ilm āsh, Abū \u27Alī al-Hasan al-Yūsī\u27s seventeenth- century al-Fahrasah, Ahmad Ibn `Ajībah\u27s nineteenth-century Fahrasah and al-Wazzānī\u27s landmark text, al-Zāwiyah, often cited as Morocco\u27s first modern Arabic novel, will be elucidated with the aim of contributing to a more nuanced understanding of the historical development of modern Moroccan prose written in Arabic. These works will be considered as a literary series with tropological shifts related primarily to the evolving role of the institution of the zāwiyah in Morocco and these authors\u27 relationship to it. All the texts draw on the same governing model based upon the Prophetic paradigm and share the same core figurative and temporal structures. It is also suggested that the evolution of these texts can be connected to the particular ideological position of the zāwiyah or tarīqah to which their authors were attached. The shift in al-Wazzanī\u27s twentieth-century al-Zāwiyah, which brings spiritual autobiographical writing in line with the modern expectations of the novel genre, can be attributed, as in the Mashriq, to its relationship with the rise of print culture. The Arabic literary history of Morocco remains largely unwritten. This project has tried to suggest a way to view part of that history outside of the common paradigm that draws a sharp distinction between the premodern and modern periods.

Antibodies Raised Against an Aβ Oligomer Mimic Recognize Pathological Features in Alzheimer’s Disease and Associated Amyloid-Disease Brain Tissue

Antibodies that target the β-amyloid peptide (Aβ) and its associated assemblies are important tools in Alzheimer's disease research and have emerged as promising Alzheimer's disease therapies. This paper reports the creation and characterization of a triangular Aβ trimer mimic composed of Aβ17-36 β-hairpins and the generation and study of polyclonal antibodies raised against the Aβ trimer mimic. The Aβ trimer mimic is covalently stabilized by three disulfide bonds at the corners of the triangular trimer to create a homogeneous oligomer. Structural, biophysical, and cell-based studies demonstrate that the Aβ trimer mimic shares characteristics with oligomers of full-length Aβ. X-ray crystallography elucidates the structure of the trimer and reveals that four copies of the trimer assemble to form a dodecamer. SDS-PAGE, size exclusion chromatography, and dynamic light scattering reveal that the trimer also forms higher-order assemblies in solution. Cell-based toxicity assays show that the trimer elicits LDH release, decreases ATP levels, and activates caspase-3/7 mediated apoptosis. Immunostaining studies on brain slices from people who lived with Alzheimer's disease and people who lived with Down syndrome reveal that the polyclonal antibodies raised against the Aβ trimer mimic recognize pathological features including different types of Aβ plaques and cerebral amyloid angiopathy