44 research outputs found
Ca 2+ -dependent autophagy is enhanced by the pharmacological agent PK11195
No full textThe 1-(2-Chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide, PK11195, is a proven enhancer of apoptotic cell death in a variety of cellular models. Recently, we have shown that by targeting the oncogene Bcl-2, PK11195 increases the [Ca ( 2+) ] in the Endoplasmic Reticulum ([Ca ( 2+) ]er) as well as IP3 induced mitochondrial ([Ca ( 2+) ]m) and cytosolic ([Ca ( 2+) ]c) Ca ( 2+) transients in HeLa cervix carcinoma cells. Here, in the same cells, we have investigated PK11195 contribution to models of pharmacologically induced macroautophagy. To do so, we have monitored the pattern of LC3 (the mammalian orthologue of yeast Atg8) distribution and post transcriptional modifications after challenging with Ca ( 2+) -dependent (ATP, Vitamin D3) and independent (Rapamycin and H 2O 2) stimuli for autophagy execution. We found that PK11195 plays a pro-autophagy role if associated with ATP and Vitamin D3 to be ineffective if co-incubated with Rapamycin and H 2O 2. Notably, Bcl-2 deletion abolished PK11195 effects thus suggesting a selective way of action against the oncogene. By these means, PK11195 is proposed as facilitator of Ca ( 2+) mediated autophagy and tool to ascertain the Bcl-2 contribution to the onset and unfolding of this essential catabolic process for cellular homeostasis
A neuropathological approach to the selective vulnerability of frontotemporal dementia.
No full textFrontotemporal dementia (FTD) is a rare neurodegenerative disorder typically emerging between ages 40 and 65, characterized by significant clinical and pathological diversity. Both sporadic and familial forms exist, with specific genetic mutations predisposing individuals to distinct pathologies. Presently, symptomatic management remains the only available care as there's no curative therapy for FTD. Clinically, FTD often manifests with social cognitive decline, including personality and behavioural changes, alongside speech impairments, word-finding difficulties, and surface dyslexia. Neuropsychiatric symptoms such as psychosis, depression, and hallucinations are also common, especially in the behavioural variant of the disease. Pathologically, FTD is marked by degeneration in the frontal and temporal cerebral lobes, termed frontotemporal lobar degeneration (FTLD). Different protein aggregations in the brain, including phosphorylated TDP-43, tau, or FUS, define various subtypes of FTLD. Major genetic mutations associated with FTD include C9orf72, GRN, and MAPT. Neuroimaging studies offer insights into brain degeneration patterns in FTD, yet predicting underlying pathologies based on clinical presentation remains challenging. Recent recognition of neuropsychiatric symptoms as early FTD indicators prompts further investigation into their correlation with underlying pathology. At the cellular level, von Economo neurons (VENs) and GABRQ-expressing pyramidal neurons are implicated in FTD's behavioural changes. Research suggests selective vulnerability of these neurons, particularly in the anterior cingulate cortex (ACC), though correlations with specific FTD subtypes remain unclear. This thesis investigates the relationship between clinical symptoms and region-specific pathology in FTD, finding potential indicators for distinguishing underlying pathologies. Additionally, it explores the correlation between neuropsychiatric symptoms and brain pathology, revealing associations suggesting broader roles for certain proteins beyond primary pathology. Further examination of VENs and GABRQ-expressing neurons in different FTD subtypes demonstrates their involvement in modulating behaviour, particularly in FTD cases with TDP-43 and FUS pathology. These findings underscore the potential diagnostic and therapeutic implications of understanding these neuronal populations in FTD. Investigations into cellular mechanisms activated in vulnerable neurons suggest responses aimed at restoring protein homeostasis, namely UPR and GVD markers, particularly in cases with dipeptide pathology. This research offers insights into potential diagnostic markers and therapeutic targets for FTD. Overall the results of this thesis support the growing evidence for the inclusion of the neuropsychiatric symptoms, hallucinations, mania and delusions to be included in the standardised diagnostic criteria for FTD. Including these key symptoms would not only improve clinical diagnostic accuracy but could also provide an opportunity to diagnose patients earlier in their disease course and in turn provide the correct care, support and future medication. In addition, we have established that VENs are part of a larger neuronal population which provides more opportunity for research. This thesis strengthens the hypothesis that the GABRQ-expressing pyramidal neurons and VENs are involved in modulating behaviour in FTD patients with TDP-43 and FUS pathology. This, together with biomarker studies, could provide a potential means of distinguishing bvFTD patients with tau pathology from those with TDP-43 or FUS pathology in clinics
The presubiculum is preserved from neurodegenerative changes in Alzheimer's disease
No full textIn the majority of affected brain regions the pathological hallmarks of Alzheimer's disease (AD) are β-amyloid (Aβ) deposits in the form of diffuse and neuritic plaques, tau pathology in the form of neurofibrillary tangles, neuropil threads and plaque-associated abnormal neurites in combination with an inflammatory response. However, the anatomical area of the presubiculum, is characterised by the presence of a single large evenly distributed 'lake-like' Aβ deposit with minimal tau deposition or accumulation of inflammatory markers. Post-mortem brain samples from sporadic AD (SAD) and familial AD (FAD) and two hereditary cerebral amyloid diseases, familial British dementia (FBD) and familial Danish dementia (FDD) were used to compare the morphology of the extracellular proteins deposited in the presubiculum compared to the entorhinal cortex. The level of tau pathology and the extent of microglial activation were quantitated in the two brain regions in SAD and FAD. Frozen tissue was used to investigate the Aβ species and proteomic differences between the two regions. Consistent with our previous investigations of FBD and FDD cases we were able to establish that the 'lake-like' pre-amyloid deposits of the presubiculum were not a unique feature of AD but they also found two non-Aβ amyloidosis. Comparing the presubiculum to the entorhinal cortex the number of neurofibrillary tangles and tau load were significantly reduced; there was a reduction in microglial activation; there were differences in the Aβ profiles and the investigation of the whole proteome showed significant changes in different protein pathways. In summary, understanding why the presubiculum has a different morphological appearance, biochemical and proteomic makeup compared to surrounding brain regions severely affected by neurodegeneration could lead us to understanding protective mechanisms in neurodegenerative diseases
Scientometric Portrait of Homi Jehangir Bhabha: The Father of Indian Nuclear Research Programme
No full textQuantitative and qualitative analysis with graphic representation of the publication productivity of a scientist facilitates easy and clear perception about the work of a scientist. Bhabha’s scientific work spanned over more than three decades (1933-1967) during which he published 104 publications, which could be classified into nine fields: Interaction of Radiation with Matter (4), Quantum Electrodynamics (5), Mathematical Physics (2), Cosmic Ray Physics (18), Elementary Particle Physics (14), Field Theory (15), General Physics (2), Nuclear Physics (4) and General (40). The highest number of publications (6) were published in 1941, 1945 and 1964 respectively. The average number of publications published per year was 3.05. His productivity coefficient was 0.05 which is a clear indicates that his publication productivity was quite consistent throughout his scientific career. He was single author in 79 of his publications and the main author in 24 publications indicates that he always preferred to work himself and lead the team as ‘mentor’. Bhabha had 22 collaborators during the period. Team of research collaborators working with a successful scientist documents the sociological aspect of history of science while generating knowledge by a leader in a domain.
Bhabha became a citable author in 1937. Bhabha received 1211 citations to his 30 publications out of 104 publications. Out of 104, 74 publications did not receive any citations. Out of 74 publications, 40 publications dealt subjects mainly of general interest. Bhabha’s 86.66 percent of cited publications received their first citations within four years of their publication indicates that his publications were noticed immediately and had direct impact among the fellow researchers working all over the world. His overall citation rate was 11.64 per cited publication. The highest citations 389 were received to the domain ‘Cosmic ray physics’. The highest number of citations received were 45 in 1938. His self-citations were only 24 (1.98%) and citations by others were 1187 (98.02%). The highest self citations were six in 1946. Bhabha’s mean diachronous self-citation rate was 1.98. The highest citation rate 28.4 was to the domain ‘Quantum electrodynamics. His single authored publications have received the highest number 863 (71.26%) of citations. Bhabha’s five publications have been cited more than 100 times each. His publications have been cited by the authors working in various diverse fields like nuclear physics, mathematical physics, instrumentation, optics, geophysics and geochemistry, condensed matter physics, applied physics, electrical and electronic engineering, mechanical engineering etc., indicating a very diverse influence and impact of Bhabha’s publications. Bhabha’s publications have also been cited by the Nobel laureates like V. L. Ginzberg, Wolfgang Pauli, H. A. Bethe, M. Born, W. Bothe, E. P. Wigner, H. Yukawa, P. M. S. Blackett and C. N. Yang which is an indication of his originality of ideas and high quality of publications
The co- immunprecipitation of HIS tagged CLCuV coat protein with HIS tagged GroEL proteins of <i>Arsenophonus</i>, <i>Portiera</i> and <i>E. coli</i>.
No full text<p>Individual HIS tagged GroEL proteins of <i>Arsenophonus</i>, <i>Portiera</i> and <i>E. coli</i> were coexpressed with HIS tagged CLCuV coat protein in <i>Rossetta gami 2 DE3 PlysS</i>. The coexpressed <i>Rossetta gami 2 DE3 PlysS</i> cell lysate was incubated with resin bound with anti-coat protein antibody (raised in rabbit). <b>Lane 1-</b> As a control <i>Arsenophonus</i> GroEL lysate was incubated with resin and anti-coat protein antibodies. No non specific band was seen hence ruling out any non specific interaction. <b>Lane 2-</b> a very faint band of <i>E.coli</i> GroEL(∼66 kDa) was seen, indicating the weak interaction of <i>E. coli</i> GroEL protein with CLCuV coat protein. <b>Lane 3-</b> no band of <i>Portiera</i> GroEL protein was observed indicating that <i>Portiera</i> GroEL protein is not interacting with CLCuV coat protein. <b>Lane 4-</b> As a control CLCuV coat protein alone was also incubated with resin and anti- coat protein antibodies. A 30 kDa band was seen showing that CLCuV coat protein was binding to anti-coat protein antibodies. <b>Lane 5-</b> A ∼66 kDa band of HIS tagged <i>Arsenophonus</i> GroEL was seen along with a 30 kDa HIS tagged CLCuV coat protein band implying there is a specific interaction between <i>Arsenophonus</i> GroEL protein and CLCuV coat protein.</p
Comparison of Spanish and Swedish Journal Indicators (Impact Factor and Self-citation Rate) in the Journal Citation Reports
No full textThe geographical and social differences between Spain and Sweden, two non-English language European countries, led to our review of the impact factors (IF) and self-citation rates of scientific journals published in these two countries. The study endeavours to compare the trends of citation rates and impact factors for all Spanish and Swedish journals indexed in the Journal Citation Reports during the time period 2000-2005
To Develop and Evaluate Children’s Cognitive Development through An AR-Playful-Learning Approach
No full textAugmented Reality (AR) technology have been recognised as an effective experience enhancer with a broad application range. It is challenging to explore such potentials in the area of learning and teaching by utilising AR features in behavioural stimulation and monitoring. In this study, the author aims at exploit AR technology to institute a system for cognitive development. The principle goal of such playful learning system is to improve the overall ability of toddlers to function in social environments through cognition forming and behavioural redirecting. This paper introduces an interactive training game that assists children between two and seven years old to develop their cognitive model through intuitive theory-based educational AR gami cation. A pilot study implements Montessori training theory is described in this paper
Frontotemporal Dementia: Correlations Between Psychiatric Symptoms and Pathology
No full textObjective: The pathology of frontotemporal dementia, termed frontotemporal lobar degeneration (FTLD), is characterized by distinct molecular classes of aggregated proteins, the most common being TAR DNA-binding protein-43 (TDP43), tau, and fused in sarcoma (FUS). With a few exceptions, it is currently not possible to predict the underlying
pathology based on the clinical syndrome. In this study, we set out to investigate the relationship between pathological
and clinical presentation at single symptom level, including neuropsychiatric features.
Methods: The presence or absence of symptoms from the current clinical guidelines, together with neuropsychiatric
features, such as hallucinations and delusions, were scored and compared across pathological groups in a cohort of
150 brain donors.
Results: Our cohort consisted of 68.6% FTLD donors (35.3% TDP-43, 28% tau, and 5.3% FUS) and 31.3% non-FTLD
donors with a clinical diagnosis of frontotemporal dementia and a different pathological substrate, such as Alzheimer’s
disease (23%). The presence of hyperorality points to FTLD rather than non-FTLD pathology (p < 0.001). Within the
FTLD group, hallucinations in the initial years of the disease were related to TDP-43 pathology (p = 0.02), including but
not limited to chromosome 9 open reading frame 72 (C9orf72) repeat expansion carriers. The presence of perseverative or compulsive behavior was more common in the TDP-B and TDP-C histotypes (p = 0.002).
Interpretation: Our findings indicate that neuropsychiatric features are common in FTLD and form an important indicator of underlying pathology. In order to allow better inclusion of patients in targeted molecular trials, the routine evaluation of patients with frontotemporal dementia should include the presence and nature of neuropsychiatric symptom
Avaliação clínica a longo prazo de pacientes obesos submetidos ao tratamento cirúrgico bariátrico no Hospital Universitário da Universidade Federal de Santa Catarina (HU-UFSC)
No full textTrabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Departamento de Clinica Medica
