פרסומים

BACKGROUND: Myelin that surrounds axons breaks in trauma and disease; e.g., peripheral nerve and spinal cord injuries (PNI and SCI) and multiple sclerosis (MS). Resulting myelin debris hinders repair if not effectively scavenged by Schwann cells and macrophages in PNI and by microglia in SCI and MS. We showed previously that myelin debris evades phagocytosis as CD47 on myelin ligates SIRPα (signal regulatory protein-α) on macrophages and microglia, triggering SIRPα to inhibit phagocytosis in phagocytes. Using PNI as a model, we tested the in vivo significance of SIRPα-dependent phagocytosis inhibition in SIRPα null mice, showing that SIRPα deletion leads to accelerated myelin debris clearance, axon regeneration and recovery of function from PNI. Herein, we tested how deletion of CD47, a SIRPα ligand and a cell surface receptor on Schwann cells and phagocytes, affects recovery from PNI.

METHODS: Using CD47 null (CD47-/-) and wild type mice, we studied myelin disruption/dismantling and debris clearance, axon regeneration and recovery of function from PNI.

RESULTS: As expected from CD47 on myelin acting as a SIRPα ligand that normally triggers SIRPα-dependent phagocytosis inhibition in phagocytes, myelin debris clearance, axon regeneration and function recovery were all faster in CD47-/- mice than in wild type mice. Unexpectedly compared with wild type mice, myelin debris clearance started sooner and CD47-deleted Schwann cells displayed enhanced disruption/dismantling and scavenging of myelin in CD47-/- mice. Furthermore, CD47-deleted macrophages from CD47-/- mice phagocytosed more myelin debris than CD47-expressing phagocytes from wild type mice.

CONCLUSIONS: This study reveals two novel normally occurring CD47-dependent mechanisms that impede myelin debris clearance. First, CD47 expressed on Schwann cells inhibits myelin disruption/dismantling and debris scavenging in Schwann cells. Second, CD47 expressed on macrophages inhibits myelin debris phagocytosis in phagocytes. The two add to a third mechanism that we previously documented whereby CD47 on myelin ligates SIRPα on macrophages and microglia, triggering SIRPα-dependent phagocytosis inhibition in phagocytes. Thus, CD47 plays multiple inhibitory roles that combined impede myelin debris clearance, leading to delayed recovery from PNI. Similar inhibitory roles in microglia may hinder recovery from other pathologies in which repair depends on efficient phagocytosis (e.g., SCI and MS).

After a traumatic childhood in Europe during the Second World War, I found that scientific research in Israel was a pleasure beyond my expectations. Over the last 65 year, I have worked on the chemistry and pharmacology of natural products. During the last few decades, most of my research has been on plant cannabinoids, the endogenous cannabinoids arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol, and endogenous anandamide-like compounds, all of which are involved in a wide spectrum of physiological reactions. Two plant cannabinoids, Δ-tetrahydrocannabinol and cannabidiol, are approved drugs. However, the endogenous cannabinoids and the anandamide-like constituents have not yet been well investigated in humans. For me, intellectual freedom-the ability to do research based on my own scientific interests-has been the most satisfying part of my working life. Looking back over the 91 years of my long life, I conclude that I have been lucky, very lucky, both personally and scientifically.

Philip Larkin’s poem “Aubade” tackles the subject of mortality with technical facility and unsparing candour. It has a reputation for profoundly affecting its readers. Yet poets Seamus Heaney and Czeslaw Milosz think “Aubade” is bad for us and for poetry: it lures us into the underworld and traps us there, and betrays poetry’s purpose by transcribing rather than transforming the depressing facts of reality. Philosophers, however, quite like it. “Aubade” crops up repeatedly in contemporary philosophy of death. I examine the various appeals that philosophers have made to Larkin’s poem with a view to drawing out subtleties in the poem and the philosophical texts, before turning my attention to broader questions of its merit. At first glance, philosophy’s affinity for “Aubade” may seem to confirm Heaney and Milosz’s contention that the poem is somehow against poetry and on the side of “reason, science, and science-inspired philosophy” (Milosz). I argue that the philosophical uses of the poem help to undercut if not entirely dissolve Heaney’s and Milosz’s polarizing efforts; they are mistaken in their views about the different purposes of poetry and philosophy, but there is some philosophical support for their commitment to averting mortal despair.

September 2022:  Kathy Behrendt is an Associate Professor of Philosophy at Wilfrid Laurier University, Canada.  She received her DPhil. from the University of Oxford, where she also taught for several years.  Behrendt has published in the areas of neo-Kantian and Parfitian reductionist theories of personal identity, narrative and anti-narrative views of the self, death, fear of death, illness, literature, and meaning in life.  She is co-founder of the International Association for the Philosophy of Death and Dying. Her current research is focused on longevity and change-intolerance, and the limits of our concern for future generations.

Dieses Buch analysiert das Verhältnis zwischen dem jemenitischen König Imam Yaḥyā Ḥamīd al-Dīn und den Juden:Jüdinnen Sanaas aus islamrechtlicher Perspektive. Es beleuchtet sowohl Imam Yahyas Dhimma-Politik als auch die Handlungsmacht von Juden:Jüdinnen als Dhimmis. Es kombiniert erstmals jüdische Erinnerungsliteratur und jemenitische Historiographie aus dem 20. Jhd. mit zum Teil bis heute grundlegenden Texten zaiditischen Rechts (fiqh) aus dem 14.-19. Jhd.

Physiological activation by light of the TRP and TRP-like (TRPL) channels requires the activation of phospholipase Cβ (PLC). The hydrolysis of phosphatidylinositol 4,5, bisphosphate (PIP) by PLC is a crucial step in the still-unclear light activation, while the generation of Diacylglycerol (DAG) by PLC seems to be involved. In this study, we re-examined the ability of a DAG analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) to activate the TRPL channels expressed in HEK cells. Unlike previous studies, we added OAG into the cytosol via a patch-clamp pipette and observed robust activation of the expressed TRPL channels. However, TRPL channel activation was much slower than the physiologically activated TRPL by light. Therefore, we used a picosecond-fast optically activated DAG analogue, OptoDArG. Inactive OptoDArG was added into the intracellular solution with the patch-clamp pipette, and it slowly accumulated on the surface membrane of the recorded HEK cell in the dark. A fast application of intense UV light to the recorded cell resulted in a robust and relatively fast TRPL-dependent current that was greatly accelerated by the constitutively active TRPL pore-region mutation. However, this current of the mutant channel was still considerably slower than the native light-induced TRPL current, suggesting that DAG alone is not sufficient for TRPL channel activation under physiological conditions.

Since its publication and first performance, Edward Albee’s Who’s Afraid of Virginia Woolf? (1962) has often been interpreted with regard to the theme of truth and illusion. A less studied but nonetheless important aspect of the play concerns its relation to C. P. Snow’s concept of the “two cultures.” This article argues for the convergence of these two discussions, resulting in an epistemological understanding of Albee. The play not only rejects the mutual alienation of the “two cultures” but also constitutes a dramatic move toward a synthesizing “third culture.” Who’s Afraid of Virginia Woolf? is read as an epistemological drama of ideas.

September 2022:  Andreas Tranvik is a PhD candidate in Comparative Literature at the Centre for Languages and Literature, Lund University. His research is primarily focused on literature as it relates to the history of knowledge. Currently, he is working on a research project about humour and knowledge in the works of the 18th century Danish-Norwegian writer Ludvig Holberg.

Weight loss interventions, including dietary changes, pharmacotherapy, or bariatric surgery, prevent many of the adverse consequences of obesity, and may also confer intervention-specific benefits beyond those seen with decreased weight alone. We compared the molecular effects of different interventions on liver metabolism to understand the mechanisms underlying these benefits. Male rats on a high-fat, high-sucrose diet underwent sleeve gastrectomy (SG) or intermittent fasting with caloric restriction (IF-CR), achieving equivalent weight loss. The interventions were compared to (AL)-fed controls. Analysis of liver and blood metabolome and transcriptome revealed distinct and sometimes contrasting metabolic effects between the two interventions. SG primarily influenced one-carbon metabolic pathways, whereas IF-CR increased lipogenesis and glycogen storage. These findings suggest that the unique metabolic pathways affected by SG and IF-CR contribute to their distinct clinical benefits, with bariatric surgery potentially influencing long-lasting changes through its effect on one-carbon metabolism.