Graduate Recital:Maria Ventura, Mezzo Soprano

Kemp Recital Hall Sunday Afternoon October 29, 2000 3:00 p.m

Study of anti-tumoral activity of HIV-Protease Inhibitor nelfinavir and identification of new nelfinavir-derivative compounds

Human Immunodeficiency Virus-Protease Inhibitors (HIV-PIs) are peptidomimetic drugs used in AIDS therapy to inhibit HIV infection by blocking viral protease. The advent of these drugs has led to a reduced incidence of HIV-associated tumors, particularly Kaposi’s sarcoma, non-Hodgkin’s lymphoma and cervical cancer. Many studies have also reported an anti-proliferative non-virological action of HIV-PIs in HIV-free models leading them to be further investigated as anti-cancer drugs. In particular HIV-PIs affect several pathways involved in tumor-cell proliferation and survival, angiogenesis, invasion, inflammation, and antitumor immunity in HIV-free models. The most effective anti-cancer HIV-PIs is nelfinavir, that is in clinical trial for several tumor types, thus encouraging the study of the intracellular pathways at the basis of their anti-tumor activity. The anti-tumoral effects of nelfinavir have been related to inhibition of Akt activation, but to date the molecular mechanism at the basis of anti-cancer activity in breast cancer is poorly understood. My results suggest an anti-proliferative activity of nelfinavir in a panel of cancer cell lines. In particular, nelfinavir induces apoptosis and necrosis in breast cancer cell lines such as MDA-MB231 and MCF-7 cells by affecting cell cycle in a cell line dependent way. The anti-tumor activity of nelfinavir is linked to the perturbation of cellular redox state; resulting in an increase of intracellular reactive oxygen species (ROS) production in breast cancer cells but not in normal breast epithelial cells. Nelfinavir treated tumor cells show also a downregulation of akt pathway due to the disruption of akt-Heat Shock Protein 90 kDa (HSP90) complex that is induced by nelfinavir and subsequent degradation of akt via proteasome. These effects result to be ROS dependent. Since treatment with anti-oxidant free radical scavenger tocopherol restores akt expression levels as well as viability of nelfinavir-untrated cells, the increase of ROS production represents the main and necessary molecular mechanism to induce cell death in breast cancer cell lines. The anti-cancer effectiveness of nelfinavir has motivated its use as lead compound in this study to design novel anti-tumoral compounds. Primary screening has led to the identification of novel nelfinavir-derivative (4n) with a high anti-cancer efficacy (IC50 50nM), that is a promising molecule to further evaluate for cancer therapy

Traditional Processing Meets Islandora

The Caltech Archives have been digitizing the papers of Paul B. MacCready, a major figure in aeronautical engineering in the second half of the 20th century. His papers include notebooks, diaries, correspondence, drawings, photographs, and audiovisual material. Islandora was chosen as the platform for access and preservation. The collection had previously been processed and a finding aid had been created. We present three innovations that have contributed to efficient digitization and ingest into Islandora, and to optimal user experience. We created a naming scheme for digitized files based on the series, box, and folder numbering of the collection. This allowed us to automatically match files with descriptive metadata and to create local identifier links as part of the ingested metadata in Islandora. We built on UCLA’s prior work to allow navigation of the collection by means of the finding aid, which is displayed in Islandora and contains links to folders. This gives intellectual context to searches. Finally, we have been working to incorporate the IIIF-compliant Universal Viewer as an additional viewer available for multipage objects

Military and elites in XXth and XXIst centuries in Argentina. Problematizing theoretical definitions and empirical uses of categories

Los militares han sido asociados con las élites sociales, económicas, políticas y estatales de la Argentina. Este artículo estudia sus relaciones desde principios del siglo XX hasta el presente. Analiza el reclutamiento de los oficiales principalmente entre las clases medias urbanas de la región pampeana; las relaciones de los oficiales con la sociabilidad de la clase alta, la construcción de su prestigio como élite moral, el aumento de sus funciones de responsabilidad social en actividades educativas, la incorporación a la élite dirigente como altos funcionarios políticos y técnicos del Estado; y su proceso de declive como élite dirigente con la pérdida de prestigio y reconocimiento social de las Fuerzas Armadas desde la crisis de la última dictadura.The military has been associated with Argentina’s social, economic, political and State elites. This article studies their relations from the beginning of the XXth century up to the present. It analyzes military recruitment carried out, mainly, in urban middle classes of the pampeana region; the officers’ relations with upper class society; the construction of military prestige as moral elite, the increase of its functions of social responsibility in educational activities, their incorporation to the ruling elite as high political and technical State officials; and its decline as ruling elite resulting from the loss of prestige and social recognition of the Armed Forces since the crisis of the last dictatorship.Fil: Soprano Manzo, Germán Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Humanidades y Ciencias Sociales. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales; ArgentinaFil: Mellado, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentin

A novel crosstalk between calcium/calmodulin kinases II and IV regulates cell proliferation in myeloid leukemia cells

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NutriLive: An Integrated Nutritional Approach as a Sustainable Tool to Prevent Malnutrition in Older People and Promote Active and Healthy Ageing—The EIP-AHA Nutrition Action Group

The present document describes a nutritional approach that is nested in the European Innovation Partnership for Active and Healthy Aging (EIP-AHA) and aims to provide the first common European program translating an integrated approach to nutritional frailty in terms of a multidimensional and transnational methodology. The document has been developed by the A3 Nutrition Action Area of the EIP-AHA and aims at providing a stepwise approach to malnutrition in older citizens, identifying adequate interventions based on a unified assessment and ICT-supported solutions. "NutriLive" is an integrated nutritional approach, represented by a structured Screening-Assessment-Monitoring-Action-Pyramid-Model (SAM-AP). Its core concept is the stratification of the nutritional needs, considered by the working group as the key for targeted, effective, and sustainable interventions. "NutriLive" tries to close gaps in epidemiological data within an aging population, creating a unified language to deal with the topic of nutrition and malnutrition in Europe. By assembling all the validated screening, assessment, and monitoring tools on malnutrition in a first pyramid, which is interrelated to a second intervention pyramid, the A3 Nutrition WG identifies a common, integrated vision on the nutritional approach to frailty, which applies to the various health care settings

Cellular subtype expression and activation of CaMKII regulate the fate of atherosclerotic plaque

Abstract Background and aims Atherosclerosis is a degenerative process of the arterial wall implicating activation of macrophages and proliferation of vascular smooth muscle cells. Calcium-calmodulin dependent kinase type II (CaMKII) in vascular smooth muscle cells (VSMCs) regulates proliferation, while in macrophages, this kinase governs diapedesis, infiltration and release of extracellular matrix enzymes. We aimed at understanding the possible role of CaMKII in atherosclerosis plaques to regulate plaque evolution towards stability or instability. Methods Clinically defined stable and unstable plaques obtained from patients undergoing carotid end arteriectomy were processed for evaluation of CaMKs protein expression, activity and localization. Results The larger content of CaMKII was found in CD14 + myeloid cells that were more abundant in unstable rather than stable plaques. To test the biological effect of activated CD14 + myeloid cells, VSMCs were exposed to the conditioned medium (CM) of macrophages extracted from carotid plaques. CM induced attenuation of CaMKs expression and activity in VSMCs, leading to the reduction of VSMCs proliferation. This appears to be due to the CaMKII dependent release of cytokines. Conclusions These results indicate a pivotal role of CaMKs in atherosclerosis by regulating activated myeloid cells on VSMCs activity. CaMKII could represent a possible target for therapeutic strategies based on macrophages specific inhibition for the stabilization of arteriosclerotic lesions

Nutrition and osteoporosis: preliminary data of campania region of european personalised ict supported service for independent living and active ageing

Background: Bone impairment and malnutrition are associated with significant disability and mortality. PERSSILAA is an European project developing health services to detect and prevent frailty in older adults by addressing cognitive, physical and nutritional. Methods: Subjects underwent anthropometric measurements, calcaneal quantitative ultrasound (QUS) scan and PREDIMED (PREvención con DIetaMEDiterránea) questionnaire. Aim: To investigate the association between adherence to the Mediterranean Diet (MD) and bone health. Results: 87 subjects (4 males and 83 females) 70.1±4.9 aged, were examined. Mean Body Mass Index (BMI) was 28.7±4.7(kg/m2): in particular 28 subjects (32.2%) resulted obese, 42 (48.3%) overweight, and only 17 (19.5%) with normal weight. Mean T score was -1.2±1.2: in particular 13 subjects (14.9%) resulted osteoporotic; 43 (49.5%) osteopenic; and 31 (35.6%) with normal bone mineral density. Regarding adherence to MD, 9 subjects (10.3%) were poorly adherent; 41 (47.2%) average adherent; 37 (42.5%) highly adherent. T-score was associated with PREDIMED score and osteoporotic nsubjects presented the lowest PREDIMED score (5.8±2.2). Conclusions: These preliminary data show a significant correlation between the adherence to the MD and bone health parameters. The association between MD and bone health highlights the potential beneficial effects of nutritional interventions promoting a Mediterranean food pattern, as safe adjuvant treatment in ageing

Identification and characterization of Cardiac Glycosides as senolytic compounds

Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.We thank Matthias Drosten, Alejo Efeyan and Sean Morrison for plasmids. F.T-M. is a postdoctoral fellow from CONACYT (cvu 268632); P.P. is a predoctoral fellow from Xunta de Galicia; M.C. is a "Miguel Servet II" investigator (CPII16/00015). P.P.-R. receives support from a program by the Deputacion de Coruna (BINV-CS/2019). Work in the laboratory of M.C. is funded by grant RTI2018-095818-B-100 (MCIU/AEI/FEDER, UE). P.J.F.-M. is funded by the IMDEA Food Institute, the Ramon Areces Foundation, (CIVP18A3891), and a Ramon y Cajal Award (MICINN) (RYC-2017-22335). M.P.I. is funded by Talento Modalidad-1 Program Grant, Madrid Regional Government (#2018-T1/BIO-11262). F.P. was funded by a Long Term EMBO Fellowship (ALTF-358-2017) and F.H-G. was funded by the PhD4MD Programme of the IRB, Hospital Clinic and IDIBAPS. Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and "laCaixa" Foundation.S

Tecnologias inovadoras do cuidado em enfermagem

Objective: to reflect about the conceptualization of technology as a field of knowledge in nursing, as well as the production of technologies in the area. Methodology: it is a theoretical reflection. Results: historically, the conception of technology is used as a product or an equipment, however, it also includes knowledge to generate and use products and organizate of human relations. The knowledge of Nursing consists of techniques and technologies produced in its praxis, as: Technologies of Nursing Care and Educational Technologies. Conclusion: however, there emerges the need to (re) to discuss the relations between technologies in nursing to contemplate the thought technology in its ambivalenceObjetivo: reflexionar sobre la conceptualización de la tecnología como un campo del conocimiento en enfermería, así como la producción de tecnologías en el área. Metodología: se trata de una reflexión teórica. Resultados: históricamente, la concepción de la tecnología es utilizada como un producto o material, sin embargo, también incluye los conocimientos para la generación y uso de los productos y la organización de las relaciones humanas. El conocimiento de Enfermería consiste en técnicas y tecnologías producidas en su praxis, como: Tecnologías de los Cuidados de Enfermería y Tecnologías Educativas. Conclusión: sin embargo, surge la necesidad de (re) discutir las relaciones entre las tecnologías en la enfermería para contemplar el pensamiento tecnológico en su ambivalencia.Objetivo: refletir acerca da conceituação de tecnologia como campo do saber de enfermagem, bem como a produção de tecnologias na área. Metodologia: Trata-se de uma reflexão teórica. Resultados: Historicamente, a concepção de tecnologia é utilizada como um produto ou equipamento, entretanto, ela também compreende saberes para geração e utilização de produtos e organização das relações humanas. O saber de Enfermagem é constituído por técnicas e tecnologias produzidas em sua práxis, como: Tecnologias do Cuidado em Enfermagem e Tecnologias Educacionais. Conclusão: Contudo, emerge a necessidade de (re) discutir as relações entre tecnologias na enfermagem para contemplar o pensamento tecnológico em sua ambivalência