APP processing and b-amyloid deposition in sporadic Creutzfeldt-Jakob patients is dependent on Dab1.

Alzheimer"s disease and prion pathologies (e.g., Creutzfeldt-Jakob disease (CJD)) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. Dab1 has been implicated in the regulation of Amyloid Precursor Protein (APP), but a direct link between human prion diseases and Dab1/APP interactions has not been published. Here we examined this putative relationship in seventeen cases of sporadic CJD (sCJD) post mortem. Biochemical analyses of brain tissue revealed two groups, which also correlated with PrPsc types 1 and 2. One group, with PrPsc type 1 showed increased Dab1 phosphorylation, and lower CTF production with an absence of A deposition. The second sCJD group, which carried PrPsc type 2, showed lower levels of Dab1 phosphorylation and CTF production, and A deposition. Thus, the present observations suggest a correlation between Dab1-phosphorylation, A deposition and PrPsc type in sCJD.

Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt-Jakob disease: a case report

Introduction: The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported. Case presentation: A 74-year-old Caucasian woman showed a sporadic Creutzfeldt-Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77. Neuropathological findings showed: spongiform change in the patient"s cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous. Conclusion: Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt-Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies

A common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob disease

The β site APP cleaving enzyme 1 (BACE1) is the rate-limiting β-secretase enzyme in the amyloidogenic processing of APP and Aβ formation, and therefore it has a prominent role in Alzheimer"s disease (AD) pathology. Recent evidence suggests that the prion protein (PrP) interacts directly with BACE1 regulating its β-secretase activity. Moreover, PrP has been proposed as the cellular receptor involved in the impairment of synaptic plasticity and toxicity caused by Aβ oligomers. Provided that common pathophysiologic mechanisms are shared by Alzheimer"s and Creutzfeldt-Jakob (CJD) diseases, we investigated for the first time to the best of our knowledge a possible association of a common synonymous BACE1 polymorphism (rs638405) with sporadic CJD (sCJD). Our results indicate that BACE1 C-allele is associated with an increased risk for developing sCJD, mainly in PRNP M129M homozygous subjects with early onset. These results extend the very short list of genes (other than PRNP) involved in the development of human prion diseases; and support the notion that similar to AD, in sCJD several loci may contribute with modest overall effects to disease risk. These findings underscore the interplay in both pathologies of APP, Aβ oligomers, ApoE, PrP and BACE1, and suggest that aging and perhaps vascular risk factors may modulate disease pathologies in part through these key players

Resolução espontânea de lesão em alça de balde do menisco medial: relato de caso e revisão da literatura

Neste trabalho é relatado um caso de lesão do menisco medial do tipo em alça de balde, que se resolveu espontaneamente. O paciente torceu o joelho esquerdo durante jogo de futebol, evoluindo com dor e bloqueio articular. A ressonância magnética realizada após o trauma demonstrou uma lesão em alça de balde do menisco medial, com fragmento deslocado na incisura intercondilar. Após tratamento clínico, o exame de controle demonstrou que havia ocorrido resolução espontânea da referida lesão.

Vieraiden grafeemien väistyminen varhaisnykysuomesta etenkin Jakob Johan Malmbergin tuotannon valossa

Summary: The abandonment of foreign graphemes in Early Modern Finnish with special reference to Jakob Johan Malmberg's works

Lapsitodistajien kertomukset Ruotsin noitatapauksissa 1668-1676

Nimeke sisällysluettelossa: ”Kirkkoherranvaimo sieppasi minut kuusi kertaa viimeyönä” : lapsitodistajat ja Blåkulla-kertomukset Ruotsin suurissa noitavainoissa.

Nervander, Johan Jakob

Johan Jakob Nervander f. 23.2.1805 i Nystad d. 15.3.1848 i Helsingfors Johan Jakob Nervander var finländsk diktare, fysiker och meteorolog, samt en nyckelfigur i Lördagssällskapet. Hans inflytande inom den finländska kultureliten var som störst på 1820-40-talen. Fast den vetenskapliga forskningen krävde största delen av Nervanders uppmärksamhet, drogs han också till diktandet. Nervanders viktigaste verk som poet är Jephtas Bok, En Minnes-Sång i Israel, som belönades med Svenska Akademiens andra pris år 1832 och trycktes åtta år senare. Nervanders lyrik var formmässigt slipad. Till innehåll och stämning varierade dikterna kraftig, från starka känslouttryck och fritt flygande fantasi till melankoli och inbundenhet. http://www.blf.fi/artikel.php?id=3567 http://www.kansallisbiografia.fi/kb/artikkeli/3567/

Gummerus, Karl Jakob

Karl Jakob Gummerus f. 13.4.1840 i Karleby d. 20.3.1898 i Helsingfors Karl Jakob Gummerus var en av de mest lästa finskspråkiga författarna under 1860- och 1870-talen, och samtidigt verksam som framgångsrik förläggare. Förlaget K.J. Gummerus, som han grundade tillsammans med sin hustru Gustava, gav i tidens folkbildande anda ut finskspråkig litteratur. Det första utgivna verket på förlaget var Gummerus egna Ylhäiset ja alhaiset (sv. Hög och låg), som baserade sig på texter utgivna som följetonger i tidningar. Detta verk som gavs ut år 1870 kan ses som den första romanen skriven på finska, även om Aleksis Kivis Sju bröder (Seitsemän veljestä) utgavs samma år. Gummerus övriga litterära produktion bestod av det han själv kallade ”uuteloita”. Det var alltså fråga om noveller, en ny litterär genre i tiden. http://www.blf.fi/artikel.php?id=2886 http://www.kansallisbiografia.fi/kb/artikkeli/2886/

Lagervall, Jakob Fredrik

Jakob Fredrik Lagervall urspr. Oxeman f. 19.7.1787 i Kontiolahti (Kontiolax) d. 7.11.1865 i Helsingfors Jakob Fredrik Lagervall har gått till historien framför allt som pionjärförfattare till finskspråkiga dramer. Lagervall var litterärt aktiv särskilt under 1830- och 1840-talen, och är främst känd som dramatiker men skrev även en del poesi och prosa. De flesta av hans dramer är religiöst färgade samt skrivna i versform och på runometer (det versmått som används i Finlands nationalepos Kalevala). Det kändaste av hans dramer är Ruunulinna (sv. Kronoborgen) från år 1834, en finsk version av William Shakespeares klassiska pjäs Macbeth. Detta drama är också den första tragedin skriven på det finska språket. Trots att Lagervall var övertygad fennoman, skrev han både på svenska och finska. http://www.kansallisbiografia.fi/kb/artikkeli/2909/

Theoremata nonnulla miscellanea (1668)

Variantti A.