The interaction between university and the users of knowledge and the functions of teaching and research : multiple case study on UNICAMP

Orientadores: Salvador Antonio Mireles Sandoval, André Luiz Sica de CamposTese (doutorado) - Universidade Estadual de Campinas, Faculdade de EducaçãoResumo: Este estudo investiga a vinculação entre a Unicamp e o meio externo, apurando seus benefícios para a universidade e suas possíveis desvantagens. A análise contou com o levantamento de dados presentes em todos os contratos dos anos de 2000 a 2012 entre a Unicamp e instituições externas, além de entrevistas com docentes de duas faculdades (Faculdade de Educação e Faculdade de Engenharia Elétrica e de Computação) para apreender a opinião e prática dos docentes sobre os contratos. Busca-se entender como estas relações interferem no funcionamento interno da universidade e como refletem nas funções de Ensino e PesquisaAbstract: This study explores the linking between Unicamp and the outside, investigating both its benefits for the university and its possible disadvantages. The analysis relied on data collection of all contracts between Unicamp and external institutions from the year 2000 until 2012. Further data was collected by conducting interviews with professors from the School of Electrical and Computer Engineering (FEEC) and the School of Education (FE), in order to understand the opinion of those involved in the contracts. The study seeks to understand how these interactions can interfere in the university¿s internal operation and effects of the Learning and Research functionsDoutoradoCiencias Sociais na EducaçãoDoutora em EducaçãoCAPE

ACAT1-associated Late Endosomes Improve NPC

We previously demonstrated that macrophages exhibit endoplasmic reticulum fragmentation under cholesterol-rich conditions, which results in the generation of acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1)-associated late endosomes/lysosomes (ACAT1-LE). ACAT1-LE efficiently esterify free cholesterol in loco, even with abnormal egress of free cholesterol from late endosomes. Because impaired free cholesterol transport from late endosomes results in Niemann-Pick type C disease (NPC), the induction of ACAT1-LE is a potential therapeutic intervention for NPC. To examine the effects of ACAT1-LE induction on intracellular cholesterol metabolism, we incubated bone marrow-derived macrophages possessing NPC phenotype (npc1–/–) with methyl-β-cyclodextrin-cholesterol complex (mβCD-cho), a cholesterol donor. Immunofluorescence confocal microscopy revealed that mβCD-cho treatment of npc1–/– macrophages resulted in significant colocalization of signals from ACAT1 and lysosome-associated membrane protein 2, a late endosome/lysosome marker. npc1–/– macrophages contained significant amounts of free cholesterol with negligible amounts of cholesteryl ester, while wild-type macrophages possessed the same amounts of both cholesterols. mβCD-cho treatment also induced marked restoration of cholesterol esterification activity. mβCD-cho administration in neonate npc1–/– mice improved survival. These results indicate that ACAT1-LE induction in npc1–/– mice corrects impaired intracellular cholesterol metabolism and that restoring cholesterol esterification improves prognosis of npc1–/–. These data suggest that ACAT1-LE induction is a potential alternative therapeutic strategy for NPC

Role of ACAT1-positive late endosomes in macrophages : Cholesterol metabolism and therapeutic applications for Niemann-Pick disease type C

Macrophages in hyperlipidemic conditions accumulate cholesterol esters and develop into foamy transformed macrophages. During this transformation, macrophages demonstrate endoplasmic reticulum fragmentation and consequently produce acyl coenzyme A : cholesterol acyltransferase 1 (ACAT1-positive late endosomes (ACAT1-LE). ACAT1-LE-positive macrophages effectively esterify modified or native low-density lipoprotein-derived free cholesterol, which results in efficient cholesterol esterification as well as atherosclerotic plaque formation. These macrophages show significant cholesterol ester formation even when free cholesterol egress from late endosomes is impaired, which indicates that free cholesterol is esterified at ACAT1-LE. Genetic blockade of cholesterol egress from late endosomes causes Niemann-Pick disease type C (NPC), an inherited lysosomal storage disease with progressive neurodegeneration. Induction of ACAT1-LE in macrophages with the NPC phenotype led to significant recovery of cholesterol esterification. In addition, in vivo ACAT1-LE induction significantly extended the lifespan of mice with the NPC phenotype. Thus, ACAT1-LE not only regulates intracellular cholesterol metabolism but also ameliorates NPC pathophysiology

Imprint cytological feature of large cell neuroendocrine carcinoma of the gallbladder : A case report

Large cell neuroendocrine carcinoma (LCNEC) is a rare poorly differentiated carcinoma with neuroendocrine differentiation showing aggressive clinical behavior. We herein report a case of gallbladder LCNEC, which was difficult to differentiate from poorly differentiated adenocarcinoma. An imprint cytology was very useful for the final diagnosis in this case. A 56-year-old male with left exophthalmos was admitted to the hospital. Radiological examinations revealed the presence of a left gallbladder tumor with orbital metastasis. The histological diagnosis was poorly differentiated adenocarcinoma, and intensive chemoradiotherapy was administered. Unfortunately, the patient died of extensive metastases 36 months after the initial onset of symptoms. An autopsy revealed a tumor mass in the gallbladder associated with multiple liver and peritoneal metastases. Imprint cytology of the main tumor revealed cytological features of LCNEC, and additional histological examinations confirmed this diagnosis. Although performing a histological examination is important for making a final diagnosis, imprint cytology is powerful tool for differential diagnosis of LCNEC, especially in patients with carcinoma with poor differentiation

Thrombospondin-1 is highly expressed in desmoplastic components of invasive ductal carcinoma of the breast and associated with lymph node metastasis

Desmoplastic (scirrhous) invasion and lymph node metastasis are critical for the treatment and prognosis of invasive ductal carcinoma of the breast. Despite being an anti-angiogenic therapeutic candidate, Thrombospondin-1 (TSP-1) promotes invasion and metastasis of some carcinomas. To clarify the effect of TSP-1 on invasion and metastasis, we obtained 101 invasive ductal carcinomas of the breast with axillary lymph node resection. All tumors were histologically divided into two categories, carcinomas with, and those with non- /minimal desmoplastic component. Immunohistochemistry for TSP-1 was performed on all primary tumors and axillary lymph nodes with tumor metastasis. Fifty-four (53.5%) of 101 tumors were recognized as positive for TSP-1 in the cytoplasm of tumor cells. Histological study showed that significantly more cancers with desmoplastic components (46/69, 66.7%) manifested TSP-1 expression than did cancers with no- or minimal (less than 20%) desmoplasia (8/32, 25.0% ; p< 0.001). Axillary lymph node metastasis was significantly higher in TSP-1-positive- (28/54, 51.9%) than TSP-1-negative cancers (11/47, 23.4% ; p<0.005). The present study indicates that tumor cells in the desmoplastic component strongly expressed TSP-1 in invasive ductal carcinoma of the breast and TSP-1 participates in invasion of these tumors. Our findings also suggest that TSP-1 promotes lymph node metastasis and TSP-1 potentially could be a predictive marker for metastasis

Iowa Mutant Apolipoprotein A-I (ApoA-IIowa) Fibrils Target Lysosomes

The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1–83) of apoA-I containing this mutation deposit as amyloid fibrils in patients’ tissues and organs, but the mechanisms of cellular degradation and cytotoxicity have not yet been clarified. In this study, we demonstrated degradation of apoA-IIowa fibrils via the autophagy-lysosomal pathway in human embryonic kidney 293 cells. ApoA-IIowa fibrils induced an increase in lysosomal pH and the cytosolic release of the toxic lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils depended on cathepsin B and was ameliorated by increasing the degradation of apoA-IIowa fibrils. Thus, although apoA-IIowa fibril transport to lysosomes and fibril degradation in lysosomes may have occurred, the presence of an excess number of apoA-IIowa fibrils, more than the lysosomes could degrade, may be detrimental to cells. Our results thus provide evidence that the target of apoA-IIowa fibrils is lysosomes, and we thereby gained a novel insight into the mechanism of AApoA1 amyloidosis

ホウシャセン タンドク リョウホウ ガ ソウコウ シタ Merkel サイボウガン ノ 1レイ

A ９１-year-old man was diagnosed with Merkel cell carcinoma after removal of a mass about １ cm in diameter from the right upper eyelid on August ５, ２０１X. Curative surgery was recommended, but the patient declined. Lymph node metastases to the right lateral angle of the eye and in front of the right ear, and cancer pain in the stump recurrence manifested. Accordingly, irradiation of the right upper eyelid was started from October ３ at ２．５Gy/fraction, and the right lateral corneal lymph nodes were included from October １１, ending at ３５ Gy in １４ fractions. From November ２２，irradiation of the lymph node metastasisin front of the right ear was started, ending at ３２. ５ Gy in １３ fractions. During irradiation, cancer pain was alleviated with opioids. Stump recurrence and lymph node metastases were decreased in size, and Computed Tomography indiated complete response. Radiation monotherapy of Merkel cell carcinoma appears to offer a treatment that should be proactively applied when curative surgery proves difficult or not desired by the patient. Use of opioids during radiotherapy may improve quality of life and enhance the therapeutic effect

CUL2-mediated clearance of misfolded TDP-43 is paradoxically affected by VHL in oligodendrocytes in ALS

The molecular machinery responsible for cytosolic accumulation of misfolded TDP-43 in amyotrophic lateral sclerosis (ALS) remains elusive. Here we identified a cullin-2 (CUL2) RING complex as a novel ubiquitin ligase for fragmented forms of TDP-43. The von Hippel Lindau protein (VHL), a substrate binding component of the complex, preferentially recognized misfolded TDP-43 at Glu246 in RNA-recognition motif 2. Recombinant full-length TDP-43 was structurally fragile and readily cleaved, suggesting that misfolded TDP-43 is cleared by VHL/CUL2 in a step-wise manner via fragmentation. Surprisingly, excess VHL stabilized and led to inclusion formation of TDP-43, as well as mutant SOD1, at the juxtanuclear protein quality control center. Moreover, TDP-43 knockdown elevated VHL expression in cultured cells, implying an aberrant interaction between VHL and mislocalized TDP-43 in ALS. Finally, cytoplasmic inclusions especially in oligodendrocytes in ALS spinal cords were immunoreactive to both phosphorylated TDP-43 and VHL. Thus, our results suggest that an imbalance in VHL and CUL2 may underlie oligodendrocyte dysfunction in ALS, and highlight CUL2 E3 ligase emerges as a novel therapeutic potential for ALS

Different forms of intervention of the foundation within the university : problems, dilemmas and solutions

Orientador: Salvador Antonio Meireles SandovalDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de EducaçãoResumo: O presente trabalho pretende explorar novas formas de atuação da sociedade para com a universidade, especificamente sob intervenção da Fundação de Desenvolvimento da UNICAMP, a FUNCAMP - instituída pela UNICAMP, é uma entidade de direito privado sem fins lucrativos, cuja finalidade é atender as demandas de pesquisa, ensino e extensão; através de gerenciamento de recursos financeiros de convênios e contratos firmados pela UNICAMP com diversas instituições. A investigação pretende entender como a UNICAMP atende a demanda das instituições externas que firmam parcerias em busca de serviços, cursos, pesquisas etc. O objetivo específico desta dissertação é levantar dados e subsídios que responda a pergunta: em que medida os contratos com intervenção da FUNCAMP levam ao "capitalismo acadêmico"? De que modo as ações praticadas avançam ou recuam no sentido de uma privatização ou de uma publicização da universidade? A amostra desse estudo se restringe aos contratos vigentes no ano de 2.005 e de 2.008, referente a seis faculdades e/ou institutos, divididos em duas diferentes áreas: humanas e engenharias. Foi possível constatar diferentes formas de abordagem nestas duas áreas, no que diz respeito aos motivos dos contratos, além de diferentes tipos das instituições e diferentes naturezas das mesmas, entre outros.Abstract: This paper aims to explore new ways of acting in society towards the university, specifically under the interventions of the Fundação de Desenvolvimento da Unicamp, FUNCAMP, established by UNICAMP; it is a private non-profits entity of which purpose is to serve the demands of research, education and extension through financial resource management agreements and contracts signed by UNICAMP with several institutions. The research intends to understand how the UNICAMP serves the demand of external institutions that have signed partnerships in search of services, courses, research etc. The specific objective of this dissertation is to collect data and information that answer the question: How do the contracts with the intervention of FUNCAMP lead to "academic capitalism"? How do the actions go forward or move back to privatize the university or make it public? The sample of this study is about the established contracts between 2005 and 2008, relating to six colleges and / or institutes that were divided into two different areas: humanities and engineering. It was possible to verify different ways to approach, related to the reasons of the contracts and different types and nature of institutions, among others things.MestradoCiencias Sociais na EducaçãoMestre em Educaçã