Protective effect of Centella asiatica against D-galactose and aluminium chloride induced rats: behavioral and ultrastructural approaches

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder and the commonest cause of dementia among the aged people. D-galactose (D-gal) is a senescence agent, while aluminium is a known neurotoxin linked to pathogenesis of AD. The combined administration of rats with d-gal and aluminium chloride (AlCl3) is considered to be an easy and a cheap method to obtain an animal model of AD. The plant Centella asiatica (CA) is reported to exert neuroprotective effects both in vitro and in vivo. Therefore, this study explored the protective effects of CA on cognition and brain ultrastructure in d-gal and AlCl3 induced rats. Materials and methods: Rats were exposed to d-gal 60 mg/kg/b.wt/day + AlCl3 200 mg/kg/b.wt/day and CA (200, 400 and 800 mg/kg/b.wt/day) and 1 mg/kg/b.wt/day of donepezil for 70 days. Different cognitive paradigms viz. T maze spontaneous alternation, modified elevated plus maze and novel object recognition test, were used to evaluate full lesions of the hippocampus, spatial learning and memory and non-spatial learning and memory respectively. Nissl’s staining was used to determine the survival of hippocampus CA1 pyramidal cells, while transmission electron microscopy was used to check the ultrastructural changes. Results: The results revealed that d-gal and AlCl3 could significantly impair behavior and cognitive functions, besides causing damage to the hippocampal CA1 pyramidal neurons in rats. In addition, it also caused ultrastructural morphological alterations in rat hippocampus. Conversely, co-administration o;f CA, irrespective of the dosage used, alleviated the cognitive impairments and pathological changes in the rats comparable to donepezil. Conclusion: In conclusion the results suggest that CA could protect cognitive impairments and morphological alterations caused by d-gal and AlCl3 toxicity in rats. Biochemical and molecular studies are ongoing to elucidate the probable pharmacodynamics of CA

Scenes from the life of a rich widow (Reval in the mid-fourteenth century)

Medieval Reval (now Tallinn) was, besides Narva, the northern most town in which Lübeck law was in force. The town received Lübeck City Rights from the Danish king, Eric Ploughpenny, in 1248. The rights were later confirmed by Queen Margaret I, who received the Duchy of Estonia as a widow’s dower, and, starting from 1266, she used the title domina Estoniae.4 Although Margaret never actually visited Estonia, she became one of the greatest benefactors of thirteenth century Reval, completing the foundation of a Cistercian monastery in Reval initiated by the Danish king, Eric Ploughpenny. She confirmed the existing possessions of the monastery, granted it the right of patronage of St. Olaf’s parish church in the old town, confirmed the possessions of the local Dominican friars located outside the city,and reaffirmed all the liberties  bestowed on the town by King Valdemar II a few decades earlier. She also made contributions to the construction of the city walls,confirmed the boundaries of the city district, issued regulations on the measures and weights to be used in the city, and granted the residents of Reval a monopoly of retail trade in cloth.

Kto i kiedy zainicjował fundację klasztoru cysterek w Dorpacie?

Celem niniejszego artykułu była próba odpowiedzi na pytanie, kto i kiedy zainicjował fundację żeńskiego klasztoru cysterskiego w estońskiej diecezji dorpackiej. Nie ulega wątpliwości, że zakładanie klasztorów żeńskich nie było sprawą priorytetową w świeżo chrystianizowanych, słabo zaludnionych i peryferyjnych Inflantach. Pierwsze klasztory męskie na tych ziemiach powstały w pierwszej dekadzie XIII w., klasztory żeńskie – dopiero na początku drugiej połowy XIII w. Fundatorami wszystkich byli lokalni władcy terytorialni – król duński i inflanccy biskupi (ryski, dorpacki i ozylski). Należy więc uznać, że podobnie było w wypadku klasztoru cysterek dorpackich, i szukać jego fundatora wśród dorpackich hierarchów. Wydaje się, że inicjatorem tej fundacji, która po raz pierwszy była wzmiankowana źródłowo dopiero w 1345 r., mógł być biskup dorpacki Frederick von Haseldorf, sprawujący tę godność w latach 1268 – ok. 1289. Sprzyjały temu stosunkowo długi czas jego pontyfikatu, potwierdzone źródłowo wcześniejsze zainteresowanie biskupa monastycyzmem kobiecym (jego rodzinny Holsztyn, Meklemburgia, Pomorze Zachodnie) oraz wysoka pozycja społeczna i majątkowa. Wydaje się, że zamiar fundacji powstał dopiero w ostatnich latach życia biskupa Fredericka von Haseldorfa i po jego śmierci przeznaczono na ten cel pieniądze sprowadzone przez dorpacką kapitułę katedralną ze Stralsundu, a stanowiące spuściznę po zmarłym biskupie. Samo powstanie klasztoru zapewne było rozciągnięte w czasie, podobnie jak w wypadku nieco lepiej oświetlonych źródłowo i wcześniejszych fundacji żeńskich klasztorów cysterek w Rydze i Rewalu, ale być może zaczął on funkcjonować jeszcze w XIII w. – zamykając okres chrystianizacji Inflant – do którego przynależały wszystkie fundacje cysterskie na terenie Dawnych Inflant

Analysis of chatbot building tools and the initial implementation

Główny cel projektu stanowiła implementacja prostego chatbota, który w przyszłości może zostać rozbudowany i wykorzystany jako chatbot Uniwersytetu Jagiellońskiego. Praca skupia się na środowiskach Bot Framework Composer oraz Power Virtual Agents - porównuje je i opisuje w jaki sposób można budować w nich chatboty. Oprócz tego omawia wybrane zagadnienia i problemy związane z tworzeniem botów. Ważnym elementem pracy jest również rozdział wyjaśniający w jaki sposób gotowego bota można opublikować w popularnych kanałach.The main goal of the project was to implement a simple chatbot that could be developed and used as a chatbot at the Jagiellonian University in the future. Our work focused on the Bot Framework Composer and Power Virtual Agents environments - we compared them and described how chatbots can be built. In addition, we discussed some issues and problems which can occur during creating bots. An important element of the work is also the chapter explaining how the finished bot can be published in popular channels

Śmierć podczas krucjat bałtyckich w kronice Henryka zwanego Łotyszem (pierwsza połowa XIII w.)

DYING DURING THE BALTIC CRUSADES, AS DESCRIBED IN HENRY OF LATVIA’S CHRONICLE (THE 1ST HALF OF THE 13TH C.) Henry “of Latvia” was an eyewitness of the events in Livonia (now the area of Latvia and Estonia) in the years 1205-1227 which he described in his chronicle. His relations of earlier events, starting from c. 1180, were based on accounts by witnesses (primarily by the Cistercian Teodoric, who later became the fi rst Estonian bishop). Henry describes the battles of Latin cru-saders with pagan tribes: the Finno-Ugrian Livonians and Estonians, the Baltic Lithuanians, Semigallians, Latgallians and Curonians, and the Rus principalities of Polotsk, Pskov and Novgorod. He notes pagan funeral customs, shocking for Christians: cremation on the battle fi eld, practiced by the Curonians, the Lithuanians’ transporting the cut-off heads of their fallen com-rades to give them a proper burial at home, or even an exchange of a Christian prisoner-of-war for the head of a dead Lithuanian. He mentions neophytes, monks and Christian knights who died a martyr’s death, killed by the pagans. He stresses that the Christians strove to spare the pagans if the latter agreed to convert. He also notes that the crusaders once murdered the garrison of a stronghold, including Estonians and Ruthenians, sparing only one man who was to pass the message to the Rus princes, as a grave memento for potential rebels. Among Henry’s many descriptions particularly interesting is one of the death and burial of Kaupo, one of Livonian magnates, a neophyte. His body was burnt and his bones were taken to his parish church to be buried. Before his death on the battlefi eld he bequeathed all his lands to the Church in Riga

Apostołowie średniowiecznych Inflant (do początku XIII w.)

Livonia, encompassing the area of today’s Latvia and Estonia, was one of the last regions of Northern Europe to be incorporated into the Christian/ Latin civilization. Its direct neighbourhood with Ruthenian duchies, which observed the Eastern Christian rite, did not contribute to the earlier conversion. It was only after late 12th century missions, organized independently of each other by the Danish Church in the form of a venture by Cistercian friar Fulco, consecrated as the Estonian bishop ca 1171–1180, as well as a grasrooots – at least in its initial phase – initiative of Augustine friar Meinhard of the Segeberg monastery in Holstein (ca 1184–1196), first bishop of Üxküll, and Cistercian friar Theodoric, active in the vicinity of Treiden (ca 1186-1202), the first abbot of Dünamünde monastery (1205-1211) and finally bishop of Estonia (1211-1219) and their successors – Cistercian friar Berthold (1197–1198), the second bishop of Üxküll and most importantly Albert, canon of the Bremen Chapter, founder of Riga and its first bishop (1199–1229) culminated with the conquest and subsequent christianisation of Livonia. They can undoubtedly be called apostles of the Barbarian Europe, although in the case of Fulco it not clearly confirmed whether his quest took place in reality. In the case of others we may speak of an initially peace mission, as attempted conversions were undertaken by setting an example to follow and doing favours to local population, in exchange for which the beneficiaries were obliged to undergo  baptism. When such tactics failed to deliver significant effects, armed crusades were organized, as a result of which the entire Livonia was formally  converted to Christianity by the end of the 13th century.Inflanty obejmujące tereny obecnej Łotwy i Estonii zostały włączone w krąg chrześcijańskiej cywilizacji łacińskiej jako jedne z ostatnich obszarów północnej Europy. Ich bezpośrednie sąsiedztwo z ruskimi księstwami, wyznającymi chrześcijaństwo w obrządku wschodnim nie przyczyniło się do ich wcześniejszej konwersji. Dopiero rozpoczęte w drugiej połowie XII w. misje, organizowane niezależnie od siebie przez Kościół duński w postaci przedsięwzięcia francuskiego cystersa Fulco, wyświęconego na biskupa Estończyków (ok. 1171–1180), jak również oddolnej – przynajmniej w początkowej fazie – inicjatywy augustiańskiego mnicha Meinharda z klasztoru w Segeberg w Holszytnie (1211-1219), pierwszego biskupa Üxküll, i cystersa Teodoryka, działającego w okolicach Treiden (ok. 1186-1202), pierwszego opata klasztoru w Dünamünde (1205-1211) i  późniejszego biskupa Estonii (1211–1219) oraz ich następców – cystersa Bertholda (1197–1198), drugiego biskupa Üxküll oraz przede wszystkim Alberta, kanonika kapituły bremeńskiej, założyciela miasta Rygi i pierwszego biskupa Rygi (1199–1229) zakończyły się podbojem i formalną chrystianizacją Inflant. Bez wątpienia wszystkich ich można nazwać apostołami barbarzyńskiej Europy, chociaż w przypadku Fulco brak jest jednoznacznego potwierdzenia, że jego wyprawa faktycznie doszła do skutku. W przypadku pozostałych mamy do czynienia początkowo z misją pokojową, gdyż starano się nawracać mocą przykładu i czynienia przysług miejscowej ludności w zamian za co zobowiązywano obdarowywanych do przyjęcia chrztu. Gdy taktyka ta przez ponad dekadę nie odniosła większych efektów, przystąpiono do organizowania zbrojnych krucjat, dzięki czemu do końca XIII w. całość Inflant została formalnie schrystianizowana

Alterations in Cerebellar Microtubule Cytoskeletal Network in a ValproicAcid-Induced Rat Model of Autism Spectrum Disorders

Autism spectrum disorders (ASD) are neurodevelopmental diseases characterised by deficits in social communication, restricted interests, and repetitive behaviours. The growing body of evidence points to a role for cerebellar changes in ASD pathology. Some of the findings suggest that not only motor problems but also social deficits, repetitive behaviours, and mental inflexibility associated with ASD are connected with damage to the cerebellum. However, the understanding of this brain structure’s functions in ASD pathology needs future investigations. Therefore, in this study, we generated a rodent model of ASD through a single prenatal administration of valproic acid (VPA) into pregnant rats, followed by cerebellar morphological studies of the offspring, focusing on the alterations of key cytoskeletal elements. The expression (Western blot) of α/β-tubulin and the major neuronal MT-associated proteins (MAP) such as MAP-Tau and MAP1B, MAP2, MAP6 (STOP) along with actin-crosslinking αII-spectrin and neurofilament light polypeptide (NF-L) was investigated. We found that maternal exposure to VPA induces a significant decrease in the protein levels of α/β-tubulin, MAP-Tau, MAP1B, MAP2, and αII-spectrin. Moreover, excessive MAP-Tau phosphorylation at (Ser396) along with key Tau-kinases activation was indicated. Immunohistochemical staining showed chromatolysis in the cerebellum of autistic-like rats and loss of Purkinje cells shedding light on one of the possible molecular mechanisms underpinning neuroplasticity alterations in the ASD brain

Inhibition of cyclin-dependent kinase 5 affects early neuroinflammatory signalling in murine model of amyloid beta toxicity

Abstract Background Cyclin-dependent kinase 5 (Cdk5) belongs to the family of proline-directed serine/threonine kinases and plays a critical role in neuronal differentiation, migration, synaptogenesis, plasticity, neurotransmission and apoptosis. The deregulation of Cdk5 activity was observed in post mortem analysis of brain tissue of Alzheimer’s disease (AD) patients, suggesting the involvement of Cdk5 in the pathomechanism of this neurodegenerative disease. However, our recent study demonstrated the important function of Cdk5 in regulating inflammatory reaction. Methods Since the role of Cdk5 in regulation of inflammatory signalling in AD is unknown, we investigated the involvement of Cdk5 in neuroinflammation induced by single intracerebroventricular (icv) injection of amyloid beta protein (Aβ) oligomers in mouse. The brain tissue was analysed up to 35 days post injection. Roscovitine (intraperitoneal administration) was used as a potent Cdk5 inhibitor. The experiments were also performed on human neuroblastoma SH-SY5Y as well as mouse BV2 cell lines treated with exogenous oligomeric Aβ. Results Our results demonstrated that single injection of Aβ oligomers induces long-lasting activation of microglia and astrocytes in the hippocampus. We observed also profound, early inflammatory response in the mice hippocampus, leading to the significant elevation of pro-inflammatory cytokines expression (e.g. TNF-α, IL-1β, IL-6). Moreover, Aβ oligomers elevated the formation of truncated protein p25 in mouse hippocampus and induced overactivation of Cdk5 in neuronal cells. Importantly, administration of roscovitine reduced the inflammatory processes evoked by Aβ in the hippocampus, leading to the significant decrease of cytokines level. Conclusions These studies clearly show the involvement of Cdk5 in modulation of brain inflammatory response induced by Aβ and may indicate this kinase as a novel target for pharmacological intervention in AD