1,416 research outputs found
Adeno-associated virus-mediated LI expression promotes functional recovery after spinal cord injury
No full textPaucity of permissive molecules and abundance of inhibitory molecules in the injured spinal cord of adult mammals prevent axons from successful regeneration and, thus, contribute to the failure of functional recovery. Using an adeno-associated viral (AAV) vector, we expressed the regeneration-promoting cell adhesion molecule L1 in both neurons and glia in the lesioned spinal cord of adult mice. Exogenous L1, detectable already 1 week after thoracic spinal cord compression and immediate vector injection, was expressed at high levels up to 5 weeks, the longest time-period studied. Dissemination of L1-transduced cells throughout the spinal cord was wide, spanning over more than 10 mm rostral and 10 mm caudal to the lesion scar. L1 was not detectable in the fibronectin-positive lesion core. L1 overexpression led to improved stepping abilities and muscle coordination during ground locomotion over a 5-week observation period. Superior functional improvement was associated with enhanced reinnervation of the lumbar spinal cord by 5-HT axons. Corticospinal tract axons did not regrow beyond the lesion scar but extended distally into closer proximity to the injury site in AAV-L1-treated compared with control mice. The expression of the neurite outgrowth-inhibitory chondroitin sulphate proteoglycan NG2 was decreased in AAV-L1-treated spinal cords, along with reduction of the reactive astroglial marker GFAP. In vitro experiments confirmed that L1 inhibits astrocyte proliferation, migration, process extension and GFAP expression. Analyses of intracellular signalling indicated that exogenous L1 activates diverse cascades in neurons and glia. Thus, AAV-mediated L1 overexpression appears to be a potent means to favourably modify the local environment in the injured spinal cord and promote regeneration. Our study demonstrates a clinically feasible approach of promising potential
The extracellular-matrix protein matrilin 2 participates in peripheral nerve regeneration.
No full textMatrilins are adaptor proteins of the extracellular matrix involved in the formation of both collagen-dependent and collagen-independent filamentous networks. Although their molecular structure and binding partners have been characterized, the functional roles of the four matrilin family members in vivo are still largely unknown. Here, we show that matrilin 2, expressed in pre-myelinating Schwann cells during normal development, profoundly influences the behaviour of glial cells and neurons in vitro. When offered as a uniform substrate, matrilin 2 increased neurite outgrowth of dorsal root ganglia (DRG) neurons and enhanced the migration of both cell line- and embryonic DRG-derived Schwann cells. Vice versa, axonal outgrowth and cell migration were decreased in DRG cultures prepared from matrilin-2-deficient mice compared with wild-type (wt) cultures. In stripe assays, matrilin 2 alone was sufficient to guide axonal growth and, interestingly, axons favoured the combination of matrilin 2 and laminin over laminin alone. In vivo, matrilin 2 was strongly upregulated in injured peripheral nerves of adult wild-type mice and failure of protein upregulation in knockout mice resulted in delayed regrowth of regenerating axons and delayed time-course of functional recovery. Strikingly, the functional recovery 2 months after nerve injury was inferior in matrilin-2-deficient mice compared with wild-type littermates, although motoneuron survival, quality of axonal regeneration, estimated by analyses of axonal diameters and degrees of myelination, and Schwann cell proliferation were not influenced by the mutation. These results show that matrilin 2 is a permissive substrate for axonal growth and cell migration, and that it is required for successful nerve regeneration
Unemployment Benefits and Unemployment Rates of Low-Skilled and Elder Workers in West Germany: A Search Equilibrium Approach
No full textApproach Author & abstract Download 16 References 1 Citations Related works & more Corrections Author Listed: Launov, Andrey ([email protected]) (University of Kent) Wolff, Joachim ([email protected]) (Institute for Employment Research (IAB), Nuremberg) Klasen, Stephan ([email protected]) (University of Göttingen) Registered: Stephan Klasen Abstract In this paper we investigate whether the extension of the entitlement to unemployment benefits in the mid 80s can explain the increase in the unemployment rates of unskilled and elder workers in western Germany. To answer this question we estimate a version of the Burdett-Mortensen search equilibrium model and analyze how workers’ search behaviour responded to these reforms. We try both nonparametric and fully-parametric estimation methods and identify the cases in which the nonparametric approach cannot be applied. We find that the entitlement reforms are largely responsible for the increase of unemployment among unskilled workers
Unemployment Benefits and Unemployment Rates of Low-Skilled and Elder Workers in West Germany: A Search Equilibrium Approach
No full textApproach Author & abstract Download 16 References 1 Citations Related works & more Corrections Author Listed: Launov, Andrey ([email protected]) (University of Kent) Wolff, Joachim ([email protected]) (Institute for Employment Research (IAB), Nuremberg) Klasen, Stephan ([email protected]) (University of Göttingen) Registered: Stephan Klasen Abstract In this paper we investigate whether the extension of the entitlement to unemployment benefits in the mid 80s can explain the increase in the unemployment rates of unskilled and elder workers in western Germany. To answer this question we estimate a version of the Burdett-Mortensen search equilibrium model and analyze how workers’ search behaviour responded to these reforms. We try both nonparametric and fully-parametric estimation methods and identify the cases in which the nonparametric approach cannot be applied. We find that the entitlement reforms are largely responsible for the increase of unemployment among unskilled workers
Saltikov-Shedrin's traditions in literary creation of Andrey Platonov
No full textIn this article the author throws light on connections between the creative work of Andrey Platonov and satire of Mikhail Saltikov-Shedrin. Author deduces similarity of the destinies of two Great Russian writers; she notifies likeness of their literary stylistics, unity of their literary characters and vehicles
In memory of Andrey A. Aleksandrov (1946?2015)
No full textOn March, 17th, 2015 professor Andrey A. Alexandrov, the chief of functional cardiology department at Endocrinology Research Centre passed away. Andrey A. Alexandrov graduated from 2nd Moscow Medical Institute in 1971. In 1979 finished his PhD and in 1989 his doctoral research on topic ?Hormonal regulation and carbohydrate metabolism in patients with heart attack?. From 1999 to present time was the Chief of cardiology department at Endocrinology Research Centre. Alexandrov is the author of more than 420 publications, he supervised 13 PhDs and 1 doctoral research. We will remember him as a high level professional, great scientist, talented teacher and charming person.
Andrey Kiselev: the life and the legend
No full textThis article is devoted to Andrey Kiselev, probably the most well-known Russian author of mathematics textbooks. His books remained in schools for nearly one hundred years, and his name became legendary, symbolizing the “good old days” when all was supposedly well with mathematics education. Meanwhile, even in Russia, let alone abroad, many aspects of Kiselev’s life are little known. Their study facilitates a better understanding of the complicated nature of the development of Russian and Soviet mathematics education, including the connection between them and seemingly distant social-political issues. The present article undertakes such a study. The author draws on his Russian publications, materials from Russian archives, and other primary sources
BOOK REVIEW “DIARY OF AN INVASION, BY ANDREY KURKOV (2022)”
No full textDiary of An Invasion is a book written by Ukrainian author Andrey Kurkov in 2022. Written mostly during the first semester of 2022, the book is a chronological and personal diary that recounts Kurkov’s experience in Ukraine, during the initial months of the Russian invasion
The Extracellular Matrix Glycoprotein Tenascin-C Is Beneficial for Spinal Cord Regeneration
No full textTenascin-C (TNC), a major component of the extracellular matrix, is strongly upregulated after injuries of the central nervous system (CNS) but its role in tissue repair is not understood. Both regeneration promoting and inhibiting roles of TNC have been proposed considering its abilities to both support and restrict neurite outgrowth in vitro. Here, we show that spontaneous recovery of locomotor functions after spinal cord injury is impaired in adult TNC-deficient (TNC(-/-)) mice in comparison to wild-type (TNC(+/+)) mice. The impaired recovery was associated with attenuated excitability of the plantar Hoffmann reflex (H-reflex), reduced glutamatergic input, reduced sprouting of monaminergic axons in the lumbar spinal cord and enhanced post-traumatic degeneration of corticospinal axons. The degeneration of corticospinal axons in TNC(-/-) mice was normalized to TNC+/+ levels by application of the alternatively spliced TNC fibronectin type III homologous domain D (fnD). Finally, overexpression of TNC-fnD via adeno-associated virus in wild-type mice improved locomotor recovery, increased monaminergic axons sprouting, and reduced lesion scar volume after spinal cord injury. The functional efficacy of the viral-mediated TNC indicates a potentially useful approach for treatment of spinal cord injury
Potentials and limitations of peripheral nerve injury models in rodents with particular reference to the femoral nerve
No full text- …
