172 research outputs found

    Modulation of EAAC1-Mediated Glutamate Uptake by Addicsin

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    Reforestation of harvested Timberlands in Mississippi: Behavior and Attitudes of Non-Industrial, Private Forest Landowners

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    Southern forests play an increasingly important role in the timber economy as per capita demand for wood continues to expand. Moreover, harvest restrictions in the Pacific Northwest in the early 1990s shifted a large portion of United States demand for softwoods to the South. In Mississippi, most of the forestland is owned by non-industrial private forest (NIPF) landowners. Approximately 314,000 NIPF landowners control 66 percent of the state’s forestland base (Hartsell and London 1995). The sizable acreage of timberland held by NIPF landowners nationally and in-state underscores the importance of their role in the timber economy and weighs heavily in the supply of raw material to the state’s $11.4 billion forest products industry (Munn 1998)

    A novel immunoscintigraphy technique using metabolizable linker with angiotensin II treatment

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    Immunoscintigraphy is a tumour imaging technique that can have specificity, but high background radioactivity makes it difficult to obtain tumour imaging soon after the injection of radioconjugate. The aim of this study is to see whether clear tumour images can be obtained soon after injection of a radiolabelled reagent using a new linker with antibody fragments (Fab), in conditions of induced hypertension in mice. Fab fragments of a murine monoclonal antibody against human osteosarcoma were labelled with radioiodinated 3′-iodohippuryl N-ɛ-maleoyl-L-lysine (HML) and were injected intravenously to tumour-bearing mice. Angiotensin II was administered for 4 h before and for 1 h after the injection of radiolabelled Fab. Kidney uptake of 125I-labelled-HML-Fab was much lower than that of 125I-labelled-Fab radioiodinated by the chloramine-T method, and the radioactivity of tumour was increased approximately two-fold by angiotensin II treatment at 3 h after injection, indicating high tumour-to-normal tissue ratios. A clear tumour image was obtained with 131I-labelled-HML-Fab at 3 h post-injection. The use of HML as a radiolabelling reagent, combined with angiotensin II treatment, efficiently improved tumour targeting and enabled the imaging of tumours. These results suggest the feasibility of PET scan using antibody fragment labelled with 18F-fluorine substitute for radioiodine. © 1999 Cancer Research Campaig

    Clinical characteristics of vulnerable populations hospitalized and diagnosed with COVID-19 in Buenos Aires, Argentina

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    There is not in Argentina publications regarding the presentation of patients with COVID-19 requiring hospitalized and emergency care in vulnerable populations (lower incomes and less education tend at greater risk for poor health status and healthcare access), and it has few reports in developing countries. The objective is to determine whether in the care of vulnerable patients, to succeed against COVID-19, multiple public health tools and interventions will be needed to minimize morbidity and mortality. The study is a prospective cohort investigation of patients with lab-confirmed COVID-19, who required to any of the Health Centers response from April 8, 2020, to August 18, 2020. In Buenos Aires Metropolitan Area (AMBA), April 8, 2020 the virus was identified in patients hospitalized in the "Southeast Network" (SN), AMBA. SN covering an area of 661 square kilometers, with 1.8 million inhabitants residing in urban, and rural areas. A total of 14 health centers with different levels of care complexity provide care to patients in the region. The information of each patient with COVID-19 evaluated by SN, was incorporated in an Epidemiological Dashboard. The investigation was designed and reported with consideration of observational studies in epidemiology. We describe the hospitals presentation and care of persons who required SN response and were ultimately diagnosed with COVID-19. From April 8, 2020, to August 18, 2020, were included 1495 patients with lab-confirmed COVID-19 in SN. A total of 58% patients were men, and the mean age (SD) was 48.9 (15.59) years. Eighty one percent patients with pre-existing diseases, most frequent hypertension and diabetes, but hypertension, chronic lung disease, and cardiovascular disease presented higher risk. A total of 13% were hospitalized in Intensive Therapy Unit. The mortality of the cohort was 9.77%. Mortality was higher for patients aged 65 or more (OR 5.09), and for those had some pre-existing disease (OR 2.61). Our observations are consistent with reports demonstrating older persons, and those with comorbidities have the highest risk of mortality related to COVID-19. However, unlike other reports from developed or some developing countries, the mortality in our study is lower. This finding may be related to age of our cohort is younger than other published. Also, the health system was able to respond to the demand.Fil: Yacobitti, A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Otero, L.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Doldan Arrubarrena, V.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Arano, J.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Lage, S.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Silberman, M.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Zubieta, M.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Erbetta, I.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Danei, P.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Baeck, G.. Hospital Mi Pueblo; ArgentinaFil: Vallejos, V.. No especifíca;Fil: Cavalli, F.. No especifíca;Fil: Calderón, N.. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Doctor Lucio Melendez.; ArgentinaFil: Di Gregorio, M.. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Doctor Lucio Melendez.; ArgentinaFil: Hernandez, V.. Hospital Dr. Arturo Oñativia - Salta Capital.; ArgentinaFil: Bruno, D.. Hospital Dr. Arturo Oñativia - Salta Capital.; ArgentinaFil: Rodera, B.. Municipalidad de Quilmes (buenos Aires). Hospital Zonal General de Agudos Doctor Isidoro Iriarte.; ArgentinaFil: Macherett, I.. Municipalidad de Quilmes (buenos Aires). Hospital Zonal General de Agudos Doctor Isidoro Iriarte.; ArgentinaFil: Parisi, M.. Municipalidad de Quilmes (buenos Aires). Hospital Zonal General de Agudos Doctor Isidoro Iriarte.; ArgentinaFil: Gallastegui, M.. Municipalidad de Quilmes (buenos Aires). Hospital Zonal General de Agudos Doctor Isidoro Iriarte.; ArgentinaFil: Paz, A.. Municipalidad de Quilmes (buenos Aires). Hospital Sub Zonal Materno Infantil Doctor Eduardo Oller.; ArgentinaFil: Bernardi, R.. No especifíca;Fil: Azcárate, S.. Gobierno de la Provincia de Buenos Aires. Hospital Provincial Evita Pueblo.; ArgentinaFil: Hraste, A.. Gobierno de la Provincia de Buenos Aires. Hospital Provincial Evita Pueblo.; ArgentinaFil: Caridi, Délida Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; ArgentinaFil: Boechi, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; ArgentinaFil: Salgado, P.. Universidad de Buenos Aires. Rectorado. Instituto de Investigaciones en Salud Pública; ArgentinaFil: Kochen, Sara Silvia. Gobierno de la Provincia de Buenos Aires. Hospital de Alta Complejidad Cuenca Alta Doctor Nestor Carlos Kirchner.; Argentina. Universidad Nacional Arturo Jauretche; Argentina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Mutations in PIK3CA are infrequent in neuroblastoma

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    BACKGROUND: Neuroblastoma is a frequently lethal pediatric cancer in which MYCN genomic amplification is highly correlated with aggressive disease. Deregulated MYC genes require co-operative lesions to foster tumourigenesis and both direct and indirect evidence support activated Ras signaling for this purpose in many cancers. Yet Ras genes and Braf, while often activated in cancer cells, are infrequent targets for activation in neuroblastoma. Recently, the Ras effector PIK3CA was shown to be activated in diverse human cancers. We therefore assessed PIK3CA for mutation in human neuroblastomas, as well as in neuroblastomas arising in transgenic mice with MYCN overexpressed in neural-crest tissues. In this murine model we additionally surveyed for Ras family and Braf mutations as these have not been previously reported. METHODS: Sixty-nine human neuroblastomas (42 primary tumors and 27 cell lines) were sequenced for PIK3CA activating mutations within the C2, helical and kinase domain "hot spots" where 80% of mutations cluster. Constitutional DNA was sequenced in cases with confirmed alterations to assess for germline or somatic acquisition. Additionally, Ras family members (Hras1, Kras2 and Nras) and the downstream effectors Pik3ca and Braf, were sequenced from twenty-five neuroblastomas arising in neuroblastoma-prone transgenic mice. RESULTS: We identified mutations in the PIK3CA gene in 2 of 69 human neuroblastomas (2.9%). Neither mutation (R524M and E982D) has been studied to date for effects on lipid kinase activity. Though both occurred in tumors with MYCN amplification the overall rate of PIK3CA mutations in MYCN amplified and single-copy tumors did not differ appreciably (2 of 31 versus 0 of 38, respectively). Further, no activating mutations were identified in a survey of Ras signal transduction genes (including Hras1, Kras2, Nras, Pik3ca, or Braf genes) in twenty-five neuroblastic tumors arising in the MYCN-initiated transgenic mouse model. CONCLUSION: These data suggest that activating mutations in the Ras/Raf-MAPK/PI3K signaling cascades occur infrequently in neuroblastoma. Further, despite compelling evidence for MYC and RAS cooperation in vitro and in vivo to promote tumourigenesis, activation of RAS signal transduction does not constitute a preferred secondary pathway in neuroblastomas with MYCN deregulation in either human tumors or murine models

    An Acetyl-Methyl Switch Drives a Conformational Change in p53

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    Individual posttranslational modifications (PTMs) of p53 mediate diverse p53-dependent responses, however much less is known about the combinatorial action of adjacent modifications. Here, we describe crosstalk between the early DNA damage response mark p53K382me2 and the surrounding PTMs that modulate binding of p53 co-factors, including 53BP1 and p300. The 1.8 Å resolution crystal structure of the tandem Tudor domain (TTD) of 53BP1 in complex with p53 peptide acetylated at K381 and dimethylated at K382 (p53K381acK382me2) reveals that the dual PTM induces a conformational change in p53. The α-helical fold of p53K381acK382me2 positions the side chains of R379, K381ac, and K382me2 to interact with TTD concurrently, reinforcing a modular design of double PTM mimetics. Biochemical and NMR analyses show that other surrounding PTMs, including phosphorylation of serine/threonine residues of p53, affect association with TTD. Our findings suggest a novel PTM-driven conformation switch-like mechanism that may regulate p53 interactions with binding partners
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