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Brain corpora amylacea, recently renamed as wasteosomes, are polyglucosan bodies that appear during aging and some neurodegenerative conditions. They collect waste substances and are part of a brain cleaning mechanism. For decades, studies on their composition have produced inconsistent results and the presence of tau protein in them has been controversial. In this work, we reanalyzed the presence of this protein in wasteosomes and we pointed out a methodological problem when immunolabeling. It is well known that to detect tau it is necessary to perform an antigen retrieval. However, in the case of wasteosomes, an excessive antigen retrieval with boiling dissolves their polyglucosan structure, releases the entrapped proteins and, thus, prevents their detection. After performing an adequate pre-treatment, with an intermediate time of boiling, we observed that some brain wasteosomes from patients with Alzheimer’s disease (AD) contained tau, while we did not detect tau protein in those from non-AD patients. These observations pointed the different composition of wasteosomes depending on the neuropathological condition and reinforce the role of wasteosomes as waste containers.

Codi del projecte: 2020PID-UB/034, A l’assignatura Fisiologia i Fisiopatologia III de 3r curs del Grau de Farmàcia de la Universitat de Barcelona s’imparteixen els continguts referents a l’anatomia, fisiologia i fisiopatologia humanes dels sistemes respiratori, renal, endocrí i reproductor. Una sessió pràctica d’aquesta assignatura es centra en l'observació al microscopi òptic de preparacions histològiques que contenen òrgans o teixit d’aquests sistemes, i està orientada a la identificació de les diferents estructures que contenen. El temps dedicat a l'observació al microscopi depèn, en bona mesura, de les habilitats de l'alumne i de la presència del professor, que ha de confirmar o corregir la identificació feta per l'alumne i donar les pautes per a una correcta interpretació de la secció de teixit. Per aquest motiu, amb el present projecte s’ha dissenyat i implementat una nova aplicació interactiva anomenada Histozoomer la qual, funcionant com un microscopi virtual, permet que l’alumne, de forma autònoma, millori l'aprenentatge en el reconeixement i interpretació de les diferents preparacions. L’aplicatiu Histozomer s’ha dissenyat de forma modular, de manera que per cada preparació histològica s’ha generat un mòdul específic de l’Histozoomer. Cada mòdul inclou la imatge virtual de la preparació, una sèrie d’activitats per facilitar el reconeixement de les estructures contingudes a la imatge, un vídeo explicatiu de la preparació, i instruccions del funcionament de l’aplicatiu. Cada mòdul ha estat dipositat al repositori INNOVADOC de la Universitat de Barcelona, i els estudiant hi poden accedir directament des del Campus Virtual amb un enllaç directe. L’aplicatiu es va implementar al campus virtual el curs 2020-21, i per tal de valorar-ne l’acceptació i adequació els estudiants van respondre una enquesta dissenyada per captar-ne el grau de satisfacció. Els estudiant van valorar positivament l’aplicació interactiva, i un 80,2% dels estudiants indicava que aquesta eina els ajudava a millorar el seu aprenentatge. A més, es va constatar que els estudiant que havien realitzat la pràctica d’histologia i a més a més havien usat el programa Histozoomer obtenien notes significativament superiors als que només havien realitzat la sessió de pràctiques. Per tot això, es conclou doncs que l’Histozoomer és una bona eina per a l’aprenentatge de la histologia, i que és un bon complement de la sessió presencial realitzada al laboratori.

The foreign body reaction is a complex biological process leading to the insulation of implanted artificial materials through a capsule of scar tissue. In particular, in chronic implantations of neural electrodes, the prediction of the scar tissue evolution is crucial to assess the implant reliability over time. Indeed, the capsule behaves like an increasing insulating barrier between electrodes and nerve fibers. However, no explicit and physically based rules are available to computationally reproduce the capsule evolution. In addition, standard approaches to this problem (i.e., Vandermonde-based and Lagrange interpolation) fail for the onset of the Runge phenomenon. More specifically, numerical oscillations arise, thus standard procedures are only able to reproduce experimental detections while they result in non physical values for inter-interval times (i.e., times before and after experimental detections). As a consequence, in this work, a novel framework is described to model the evolution of the scar tissue thickness, avoiding the onset of the Runge phenomenon. This approach is able to provide novel approximating functions correctly reproducing experimental data (R2≃0.92) and effectively predicting inter-interval detections. In this way, the overall performances of previous approaches, based on phenomenological fitting polynomials of low degree, are improved.

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Leptin, as a nutritional inhibitor by repressing food intake, is critical compromised in the major common forms of obesity. Skeletal muscle is the main effector tissue for energy expenditure modifications by the effect of endocrine axes, such as leptin signaling. Our study has been carried out using skeletal muscle from leptin-deficient animal model, in order to ascertain the importance of this hormone in eating disorders. Here we report that leptin-deficiency stimulates an uncontrolled oxidative phosphorylation metabolism, resulting in an excess of energy production that culminates in mitochondrial dysfunction. Thus, different nutrient sensing pathways are perturbed, loosing proteostasis and promoting lipid anabolism, that induces myofiber degeneration and drives oxidative type I fiber conversion. Melatonin treatment plays a significant role in regulating energy homeostasis and fuel utilization. This study reveals melatonin to be a decisive mitochondrial function-fate regulator, with implications for resembling physiological energy requirements and targeting glycolytic type II fibers recovery.

Made available in DSpace on 2018-08-01T21:35:04Z (GMT). No. of bitstreams: 1 tese_12099_Dissertação_Isabella Bittencourt da Valle.pdf: 8090609 bytes, checksum: 6e09574c3fb07de58cf9e66e8e26d822 (MD5) Previous issue date: 2018-04-23 O prognóstico de pacientes com Carcinoma Epidermóide Oral (CEO) é majoritariamente desfavorável, principalmente devido à elevada taxa de recidiva e mortalidade. Até o momento, não existem marcadores biológicos clinicamente disponíveis que indiquem eventos de transformação tumoral ou prognóstico em CEO. Portanto, grande interesse tem sido direcionado aos genes reguladores do ciclo celular, como a participação da expressão gênica de P63 na oncogênese através da sua atividade na regulação da proliferação e diferenciação celular em CEO. Este trabalho teve como objetivo analisar a aplicabilidade de p63 como biomarcador de prognóstico e progressão tumoral. Realizou-se estudo multicêntrico internacional, no qual foram obtidas amostras biológicas, dados clínicos e seguimento clínico de 109 indivíduos com CEO provenientes do Brasil e Reino Unido. As lâminas histológicas obtidas foram avaliadas quanto à gradação tumoral, infiltrado linfocitário tumoral (TIL), padrão de invasão tumoral e invasão perineural, vascular e linfática. Tissue Microarray (TMA) foi construído considerando 3 áreas: epitélio adjacente ao tumor, displasia e tumor. Os TMAs foram submedidos à imunohistoquímica para análise de expressão de p63 e p40 (ΔNp63) e hibridização in situ de RNA para investigar p63 mRNA. Para avaliar a expressão de p63 e p40 foi considerada a marcação nuclear em queratinócitos através de H-Score. A avaliação de p63 mRNA se deu por um guia de pontuação (score 0-4) conforme a quantidade de pontos em cada célula. O nível de significância considerado para todos os testes estatísticos foi de 95%. Teste Qui-Quadrado foi empregado para instituir associações entre as variáveis clinico-patológicas estudadas. A comparação entre a expressão da proteína p63, p40 e de p63 mRNA nas diferentes regiões foi realizada através do teste de Wilcoxon. Curvas de sobrevida global e sobrevida livre de doença foram obtidas pelo modelo de Kaplan-Meier e regressão de Cox. Nossos resultados mostraram associação entre a elevada presença de TIL no tumor com estadiamentos iniciais (p=0,001) enquanto tabagismo mostrou relação com menor TIL (p=0,044) e padrões de invasão tumoral dos tipos III e IV (p=0,032). Indivíduos etilistas/ex-etilistas apresentaram mais invasão vascular que os não etilistas (p=0,015). A expressão de p63 nos tumores foi maior que nas displasias (p=0,001) e foi associada a tumores maiores (T3 e T4) (p=0,001). Foi observada diferença quanto à expressão de p40 entre displasia e tumor (p

The additional file contains: a section where we show our fitting method performance on different synthetic data sets; a section where we show the plot of gamma and stretched exponential fit results for CG interdistance distribution of Homo sapiens; a section where we show how we calculated errors on r-squared, based on Olkin and Finnâ s approximation; a final section where we collected into two tables all the informations about the analysis perfomed on the 4425 organisms. The first table contains informations about organism type and identification on NCBI website; the second contains gamma fit parameters, ratio of unkown nucleotides (%N), ratio of CG dinucleotides (%CG) and r-squared values. (PDF 1960 kb)

We propose an index to measure the degree of ability or desire of the population in a given country to have children, via an analysis of certain factors that may have a positive or negative influence on the fertility rate of that country. Using data for the twenty-eight countries of the European Union, and Principal Components Analysis, we construct the International Multidimensional Fertility Index as a combination of four dimensions: (1) Economy and family, (2) Attitudes and habits, (3) Work–Life Balance, and (4) Policy, along with nineteen distinct variables. We find that Denmark, the Netherlands, and Luxembourg are among the countries with the highest value of the index, and they also have high fertility rates within the EU. At the other end of the spectrum, Latvia, Cyprus, and Greece, are ranked in the last positions according to our index, countries that also present low values in their fertility rates. We also find a positive correlation between the value of our index and country fertility rates, an indication that our index may be capturing country differences in the conditions for bearing children, with higher values of the index indicating better conditions for childbirth and childrearing. To the extent that international data becomes available, our methodology will allow for the construction of international rankings, helpful in identifying cross-country differences in the conditions for fertility.

Introduction: ADHD is characterized by inattention, hyperactivity, impulsivity, or a combination of these symptoms. Sleep disorders may be considered as a not secondary underlying cause of ADHD and growing evidence evidenced that obstructive sleep apnea syndrome (OSA) symptoms may overlap ADHD's ones. Aim of the present study is verifying the presence of ADHD-like symptoms in other frequent condition such as sleep-related breathing disorders in pediatric age. Materials and methods: 34 children (19 males and 15 females) aged 6-10 years (mean age 9.706 ± 3.434) with polysomnographic diagnosis of OSA, according to ICSD-3 criteria, were recruited. Control group was composed by 89 typical developing children (47 males, 42 females) (mean age 9,528 ± 3,351). The Conners' Rating Scale- Revised (CRS-R) test was administered to mothers to assess their children's behavior. Results: The two groups are comparable for age (p = 0.794) and sex distribution (p = 0.918). Subjects affected by OSA present higher scores in pathological range in all scales of CRS-R than controls (Table 1). Conclusions: Scientific and clinical evidences tend to stress the similarities between ADHD and OSA effects/comorbidities in pediatric age, suggesting sleep screening as mandatory before starting stimulant drugs treatment.

Introduction: Childhood absence epilepsy (CAE) is a common type of pediatric idiopathic generalized epilepsy, characterized by multiple seizures of typical absence, with typical EEG pattern consisting in bilateral synchronous and symmetrical discharges of generalized 3 Hz spike-wave (SWDs). Recently, some researchers have suggested that the underlying epileptogenic mechanism of absence seizures selectively involves the frontal cortical circuits, also supported by video-electroencephalography data(3). These data may be considered as a new window in CAE comprehension and management, particularly about symptoms different from seizure that children affected may present. In this light, aim of the present study is evaluating the presence of internalizing problems in prepubertal children affected by CAE. Material and methods: 18 patients (10 females, 8 males) ranging age from 8-11 years (mean age 9.36 ± 1.32) affected by typical CAE were recruited. Control group was composed by 43 subjects (32 females, 11 males) (mean age 8.54 ± 2.01). All subjects were screened for internalizing symptoms with SAFA-A scale and CDI test. Results: The two groups were comparable for age (p=0.117) and sex distribution (p=0.251). CAE children showed significantly higher score than controls for anxiety (p

[cat] La malaltia d'Alzheimer (MA) es caracteritza per la presència a l'hipocamp i l'escorça de plaques senils de la proteïna β-amilode (Aβ), cabdells neurofibrilars de la proteïna tau hiperfosforilada i pèrdua de sinapsis. La hipòtesi neurovascular de la MA dóna una especial importància a les alteracions de la Barrera Hematoencefàlica (BHE) i els increments de la proteïna β-amilode (Aβ). Els ratolins modificats genèticament són els models animals més utilitzats en la investigació de la MA. Tanmateix, aquests ratolins imiten aspectes de la MA de tipus familiar, on alteracions genètiques predisposen a patir la malaltia. Els ratolins d'edat avançada poden ajudar a discernir la frontera entre l'envelliment normal i el patològic. En aquest context prenen especial rellevància els ratolins amb senescència accelerada SAMP8. Aquesta soca ja ha estat descrita com a model de MA i presenta vàries característiques de la MA com dèficits en l'aprenentatge i la memòria, alteracions emocionals, nivells elevats d'APP i Aβ, patologia neuronal associada a tau, alteracions en el sistema colinèrgic, neurodegeneració i estrès oxidatiu entre d'altres. En aquesta tesi hem investigat: 1-Les alteracions i l'evolució temporal de les modificacions en la integritat de la BHE en escorça i hipocamp de ratolins SAMP8; 2-La presència de dipòsits amiloides en aquests ratolins a les zones cerebrals abans esmentades així com el seu increment amb l'edat i 3-La relació temporal i en la localització de les alteracions de la BHE i els dipòsits d'Aβ d'aquests ratolins. Les conclusions que hem estret són que en ratolins SAMP8: 1- Presenten alteracions de la BHE a partir dels 9 mesos d'edat. 2- Presenten acumulacions d'Aβ a partir de 6 mesos d'edat. 3- Presenten nivells més elevats d'angiopatia amiloïdal cerebral (CAA) a partir dels 3 mesos d'edat. 4- Tots els vasos amb CAA mostren també alteracions de la BHE, tot i que hi ha altres basos amb la BHE alterada sense CAA. 5- No hi ha relació directa entre la localització dels dipòsits amiloides i la localització dels vasos sanguinis, els vasos amb CAA ni amb els vasos amb la BHE alterada.

La malaltia d'Alzheimer (MA) es caracteritza per la presència a l'hipocamp i l'escorça de plaques senils de la proteïna β-amilode (Aβ), cabdells neurofibrilars de la proteïna tau hiperfosforilada i pèrdua de sinapsis. La hipòtesi neurovascular de la MA dóna una especial importància a les alteracions de la Barrera Hematoencefàlica (BHE) i els increments de la proteïna β-amilode (Aβ). Els ratolins modificats genèticament són els models animals més utilitzats en la investigació de la MA. Tanmateix, aquests ratolins imiten aspectes de la MA de tipus familiar, on alteracions genètiques predisposen a patir la malaltia. Els ratolins d'edat avançada poden ajudar a discernir la frontera entre l'envelliment normal i el patològic. En aquest context prenen especial rellevància els ratolins amb senescència accelerada SAMP8. Aquesta soca ja ha estat descrita com a model de MA i presenta vàries característiques de la MA com dèficits en l'aprenentatge i la memòria, alteracions emocionals, nivells elevats d'APP i Aβ, patologia neuronal associada a tau, alteracions en el sistema colinèrgic, neurodegeneració i estrès oxidatiu entre d'altres. En aquesta tesi hem investigat: 1-Les alteracions i l'evolució temporal de les modificacions en la integritat de la BHE en escorça i hipocamp de ratolins SAMP8; 2-La presència de dipòsits amiloides en aquests ratolins a les zones cerebrals abans esmentades així com el seu increment amb l'edat i 3-La relació temporal i en la localització de les alteracions de la BHE i els dipòsits d'Aβ d'aquests ratolins. Les conclusions que hem estret són que en ratolins SAMP8: 1- Presenten alteracions de la BHE a partir dels 9 mesos d'edat. 2- Presenten acumulacions d'Aβ a partir de 6 mesos d'edat. 3- Presenten nivells més elevats d'angiopatia amiloïdal cerebral (CAA) a partir dels 3 mesos d'edat. 4- Tots els vasos amb CAA mostren també alteracions de la BHE, tot i que hi ha altres basos amb la BHE alterada sense CAA. 5- No hi ha relació directa entre la localització dels dipòsits amiloides i la localització dels vasos sanguinis, els vasos amb CAA ni amb els vasos amb la BHE alterada.

This report provides the findings of the evaluation of the early education pilot for disadvantaged two year old children (the pilot). This study aimed to assess the impact of the pilot by looking at: how well the pilot was targeted, parents’ experiences of taking up a pilot place, the quality of the pilot settings, the impact on the children’s behaviour, and parents’ views and experiences of using a pilot place. The pilot provided free early years education to over 13,500 disadvantaged two year olds between 2006 and 2008. The main purpose of the pilot was to improve children’s social and cognitive outcomes, e.g. their social confidence and independence, and their verbal skills and reasoning ability. Additional aims were to have a positive impact on children’s parents and wider family e.g. on the relationship between parents and their children, or on parent’s emotional wellbeing. The funding offered these children 7.5 or in a small number of local authorities 12.5 hours of early years education per week for 38 weeks of the year. The pilot places were available in a variety of early years settings e.g. nurseries, play groups and with childminders, but all were required to operate the Birth to Three Matters curriculum.

This study assessed the impact of NNI on parental employment, use of formal childcare, and take-up of benefits and tax credits, particularly for disadvantaged groups such as lone parents, low income families and ethnic minority groups.

As part of its welfare to work strategy the Government has been concerned to encourage and increase lone parents' participation in the labour market and has set itself the target of an employment rate of 70 per cent for lone parents by 2010. Research findings over the course of the last ten years or so have shown that childcare is an important contributing factor in the labour market behaviour of lone parents. This report presents findings from qualitative research to increase understanding of lone parents' attitudes towards and experiences of childcare, their decisions about childcare and work, and their views and experiences of recent and imminent policy initiatives and changes. (It should be noted that this report was drafted prior to the Government's childcare strategy announcements in December 2004).

One of the problems associated with the modern biomaterials used in prostheses is osteolysis, which, although its exact origin is unknown, has been associated with wear particles. Osteoblasts seem to participate directly in this phenomenon. This paper investigates in vitro cellular response to the wear particles from the metal substrate and ceramic covering (α-alumina) of a new titanium yttrium aluminum alloy, MA 956, that has been proposed as a biomaterial because of its exceptional mechanical and electrochemical properties. The effect of different sizes (10 and 80 μm) of MA 956 and α-alumina particles on osteoblast function was studied in primary human bone cell cultures. Cells were harvested from trabecular bone fragments obtained during knee arthroplasty. Osteoblastic cell response to the particles was measured by assaying C-terminal type I procollagen (PICP), alkaline phosphatase, and osteocalcin secretion, with and without 1.25(OH)2D3 stimulation, in the cell-conditioned medium. Both sizes of MA 956 and α-alumina particles decreased PICP secretion in nonstimulated osteoblastic cells, but this secretion was not affected in the cultures stimulated with 1.25(OH)2D3. Only the 10 μm μ-alumina particles inhibited alkaline phosphatase activity in 1.25(OH)2D3-stimulated and nonstimulated cultures. The rise in osteocalcin levels after 1.25(OH)2D3 stimulation was lower in the presence of the 10 μm MA 956 particles than in the presence of α-alumina particles. Although both materials seem to have directly affected in vitro osteoblastic cell function, the increase in osteocalcin levels after 1.25(OH)2D3 stimulation was lower after exposure to MA 956 particles than the increase observed after exposure to α-alumina particles. Therefore, it does not seem that osteocalcin stimulated bone resorption, suggesting that MA 956 would be less likely to provoke osteolysis. (C) 2000 John Wiley and Sons, Inc. | One of the problems associated with the modern biomaterials used in prostheses is osteolysis, which, although its exact origin is unknown, has been associated with wear particles. Osteoblasts seem to participate directly in this phenomenon. This paper investigates in vitro cellular response to the wear particles from the metal substrate and ceramic covering (α-alumina) of a new titanium yttrium aluminum alloy, MA 956, that has been proposed as a biomaterial because of its exceptional mechanical and electrochemical properties. The effect of different sizes (10 and 80 μm) of MA 956 and α-alumina particles on osteoblast function was studied in primary human bone cell cultures. Cells were harvested from trabecular bone fragments obtained during knee arthroplasty. Osteoblastic cell response to the particles was measured by assaying C-terminal type I pro-collagen (PICP), alkaline phosphates, and osteocalcin secretion, with and without 1.25(OH)2D3 stimulation, in the cell-conditioned medium. Both sizes of MA 956 and α-alumina particles decreased PICP secretion in nonstimulated osteoblastic cells, but this secretion was not affected in the cultures stimulated with 1.25(OH)2D3. Only the 10 μm α-alumina particles inhibited alkaline phosphatase activity in 1.25(OH)2D3-stimulated and nonstimulated cultures. The rise in osteocalcin levels after 1.25(OH)2D3 stimulation was lower in the presence of the 10 μm MA 956 particles than in the presence of α-alumina particles. Although both materials seem to have directly affected in vitro osteoblastic cell function, the increase in osteocalcin levels after 1.25(OH)2D3 stimulation was lower after exposure to MA 956 particles than the increase observed after exposure to α-alumina particles. Therefore, it does not seem that osteocalcin stimulated bone resorption, suggesting that MA 956 would be less likely to provoke osteolysis.