470 research outputs found
Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231
Golgi phosphoprotein 3 (GOLPH3) has been implicated in the development of carcinomas in many human tissues, and is currently considered a bona fide oncoprotein. Importantly, several tumor types show overexpression of GOLPH3, which is associated with tumor progress and poor prognosis. However, the underlying molecular mechanisms that connect GOLPH3 function with tumorigenicity are poorly understood. Experimental evidence shows that depletion of GOLPH3 abolishes transformation and proliferation of tumor cells in GOLPH3-overexpressing cell lines. Conversely, GOLPH3 overexpression drives transformation of primary cell lines and enhances mouse xenograft tumor growth in vivo. This evidence suggests that overexpression of GOLPH3 could result in distinct features of GOLPH3 in tumor cells compared to that of non-tumorigenic cells. GOLPH3 is a peripheral membrane protein mostly localized at the trans-Golgi network, and its association with Golgi membranes depends on binding to phosphatidylinositol-4-phosphate. GOLPH3 is also contained in a large cytosolic pool that rapidly exchanges with Golgi-associated pools. GOLPH3 has also been observed associated with vesicles and tubules arising from the Golgi, as well as other cellular compartments, and hence it has been implicated in several membrane trafficking events. Whether these and other features are typical to all different types of cells is unknown. Moreover, it remains undetermined how GOLPH3 acts as an oncoprotein at the Golgi. Therefore, to better understand the roles of GOLPH3 in cancer cells, we sought to compare some of its biochemical and cellular properties in the human breast cancer cell lines MCF7 and MDA-MB-231 with that of the non-tumorigenic breast human cell line MCF 10A. We found unexpected differences that support the notion that in different cancer cells, overexpression of GOLPH3 functions in diverse fashions, which may influence specific tumorigenic phenotypes
Optimizing DDRADseq in non-model species: A Case Study in Eucalyptus dunnii Maiden
Restriction site-associated DNA sequencing (RADseq) and its derived protocols, such as double digest RADseq (ddRADseq), offer a flexible and highly cost-effective strategy for efficient plant genome sampling. This has become one of the most popular genotyping approaches for breeding, conservation, and evolution studies in model and non-model plant species. However, universal protocols do not always adapt well to non-model species. Herein, this study reports the development of an optimized and detailed ddRADseq protocol in Eucalyptus dunnii, a non-model species, which combines different aspects of published methodologies. The initial protocol was established using only two samples by selecting the best combination of enzymes and through optimal size selection and simplifying lab procedures. Both single nucleotide polymorphisms (SNPs) and simple sequence repeats (SSRs) were determined with high accuracy after applying stringent bioinformatics settings and quality filters, with and without a reference genome. To scale it up to 24 samples, we added barcoded adapters. We also applied automatic size selection, and therefore obtained an optimal number of loci, the expected SNP locus density, and genome-wide distribution. Reliability and cross-sequencing platform compatibility were verified through dissimilarity coefficients of 0.05 between replicates. To our knowledge, this optimized ddRADseq protocol will allow users to go from the DNA sample to genotyping data in a highly accessible and reproducible way.Instituto de BiotecnologĂaFil: Aguirre, Natalia Cristina. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Filippi, Carla Valeria. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Zaina, Giusi. University of Udine. Department of Agricultural, Food, Environmental and Animal Sciences; ItaliaFil: Rivas, Juan Gabriel. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Acuña, Cintia Vanesa. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Villalba, Pamela Victoria. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Garcia, Martin Nahuel. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Gonzalez, Sergio Alberto. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Rivarola, Maximo Lisandro. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Martinez, Maria Carolina. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Puebla, Andrea Fabiana. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Morgante, Michele. University of Udine. Department of Agricultural, Food, Environmental and Animal Sciences; ItaliaFil: Hopp, Horacio Esteban. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Paniego, Norma Beatriz. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Marcucci Poltri, Susana Noemi. Instituto Nacional de TecnologĂa Agropecuaria (INTA). Instituto de BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentin
The impact of socioeconomic and phenotypic traits on self-perception of ethnicity in Latin America
Self-perception of ethnicity is a complex social trait shaped by both, biological and non-biological factors. We developed a comprehensive analysis of ethnic self-perception (ESP) on a large sample of Latin American mestizos from five countries, differing in age, socio-economic and education context, external phenotypic attributes and genetic background. We measured the correlation of ESP against genomic ancestry, and the influence of physical appearance, socio-economic context, and education on the distortion observed between both. Here we show that genomic ancestry is correlated to aspects of physical appearance, which in turn affect the individual ethnic self-perceived ancestry. Also, we observe that, besides the significant correlation among genomic ancestry and ESP, specific physical or socio-economic attributes have a strong impact on self-perception. In addition, the distortion among ESP and genomic ancestry differs across age ranks/countries, probably suggesting the underlying effect of past public policies regarding identity. Our results indicate that individuals’ own ideas about its origins should be taken with caution, especially in aspects of modern life, including access to work, social policies, and public health key decisions such as drug administration, therapy design, and clinical trials, among others
Using an Ellipsoid Model to Track and Predict the Evolution and Propagation of Coronal Mass Ejections
We present a method for tracking and predicting the propagation and evolution
of coronal mass ejections (CMEs) using the imagers on the STEREO and SOHO
satellites. By empirically modeling the material between the inner core and
leading edge of a CME as an expanding, outward propagating ellipsoid, we track
its evolution in three-dimensional space. Though more complex empirical CME
models have been developed, we examine the accuracy of this relatively simple
geometric model, which incorporates relatively few physical assumptions,
including i) a constant propagation angle and ii) an azimuthally symmetric
structure. Testing our ellipsoid model developed herein on three separate CMEs,
we find that it is an effective tool for predicting the arrival of density
enhancements and the duration of each event near 1 AU. For each CME studied,
the trends in the trajectory, as well as the radial and transverse expansion
are studied from 0 to ~.3 AU to create predictions at 1 AU with an average
accuracy of 2.9 hours.Comment: 18 pages, 11 figure
Serous cystic neoplasm of the pancreas: A multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas)
OBJECTIVES:
Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality.
DESIGN:
Retrospective multinational study including SCN diagnosed between 1990 and 2014.
RESULTS:
2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58\u2005years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40\u2005mm (2-200)), 9% had resection beyond 1\u2005year of follow-up (3\u2005years (1-20), size at diagnosis: 25\u2005mm (4-140)) and 39% had no surgery (3.6\u2005years (1-23), 25.5\u2005mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1\u2005year (n=1271), size increased in 37% (growth rate: 4\u2005mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1).
CONCLUSIONS:
After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN
Rethinking palliative care in a public health context: addressing the needs of persons with non-communicable chronic diseases
Non-communicable chronic diseases (NCCDs) are the main cause of morbidity and mortality globally. Demographic aging has resulted in older populations with more complex healthcare needs. This necessitates a multilevel rethinking of healthcare policies, health education and community support systems with digitalization of technologies playing a central role. The European Innovation Partnership on Active and Healthy Aging (A3) working group focuses on well-being for older adults, with an emphasis on quality of life and healthy aging. A subgroup of A3, including multidisciplinary stakeholders in health care across Europe, focuses on the palliative care (PC) model as a paradigm to be modified to meet the needs of older persons with NCCDs. This development paper delineates the key parameters we identified as critical in creating a public health model of PC directed to the needs of persons with NCCDs. This paradigm shift should affect horizontal components of public health models. Furthermore, our model includes vertical components often neglected, such as nutrition, resilience, well-being and leisure activities. The main enablers identified are information and communication technologies, education and training programs, communities of compassion, twinning activities, promoting research and increasing awareness amongst policymakers. We also identified key 'bottlenecks': inequity of access, insufficient research, inadequate development of advance care planning and a lack of co-creation of relevant technologies and shared decision-making. Rethinking PC within a public health context must focus on developing policies, training and technologies to enhance person-centered quality life for those with NCCD, while ensuring that they and those important to them experience death with dignity
Controlled reduction of photobleaching in DNA origami gold nanoparticle hybrids
The amount of information obtainable from a fluorescence-based measurement is limited by photobleaching: Irreversible photochemical reactions either render the molecules nonfluorescent or shift their absorption and/or emission spectra outside the working range. Photobleaching is evidenced as a decrease of fluorescence intensity with time, or in the case of single molecule measurements, as an abrupt, single-step interruption of the fluorescence emission that determines the end of the experiment. Reducing photobleaching is central for improving fluorescence (functional) imaging, single molecule tracking, and fluorescence-based biosensors and assays. In this single molecule study, we use DNA self-assembly to produce hybrid nanostructures containing individual fluorophores and gold nanoparticles at a controlled separation distance of 8.5 nm. By changing the nanoparticles? size we are able to systematically increase the mean number of photons emitted by the fluorophores before photobleaching.Fil: Pellegrotti, Jesica Vanesa. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de FĂsica; ArgentinaFil: Acuña, Guillermo. Technische Universität Braunschweig. Institute for Physical and Theoretical Chemistry. NanoBioSciences Group; AlemaniaFil: Puchkova, Anastasiya. Technische Universität Braunschweig. Institute for Physical and Theoretical Chemistry. NanoBioSciences Group; AlemaniaFil: Holzmeister, Phil. Technische Universität Braunschweig. Institute for Physical and Theoretical Chemistry. NanoBioSciences Group; AlemaniaFil: Gietl, Andreas. Technische Universität Braunschweig. Institute for Physical and Theoretical Chemistry. NanoBioSciences Group; AlemaniaFil: Lalkens, Birka. Technische Universität Braunschweig. Institute for Physical and Theoretical Chemistry. NanoBioSciences Group; AlemaniaFil: Stefani, Fernando Daniel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de FĂsica; ArgentinaFil: Tinnefeld, Philip. Technische Universität Braunschweig. Institute for Physical and Theoretical Chemistry. NanoBioSciences Group; Alemani
Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance
Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample
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