An Epistemological Account of Indoctrination

What is indoctrination? This work aims to persuade the reader that a promising approach to answering this question is conducting—in Haslanger’s (2000) terminology—a descriptive analysis of indoctrination from an epistemological viewpoint. To do so, I argue that the epistemological viewpoint is a privileged one because it encompasses all instances of indoctrination, and that a descriptive kind of analysis is the most appropriate to improve our understanding of an often mischaracterised phenomenon. Further, to show that the suggested approach is fruitful, I develop an account of indoctrination along these lines. I develop my account in dialogue with the literature on indoctrination in Analytic Philosophy, where indoctrination is generally understood as a degenerate form of proper education, and where efforts are mostly devoted to explicating why indoctrination deviates from proper education. Against this tradition, and borrowing from the literature on manipulation instead, I argue that indoctrination is rather the exploitation of an epistemic-cum-cognitive vulnerability. It consists not in inculcating beliefs, but in instilling a defective pattern of response to reasons, which leads the subject of indoctrination to systematically choose to do the manipulator's bidding. The challenge then is not distinguishing indoctrination from proper education, but from other defective forms of reasoning

Cancer profiles by affinity propagation

The affinity propagation algorithm is applied to a problem of breast cancer subtyping using traditional biologic markers. The algorithm provides a procedure to determine the number of profiles to be considered. A well know breast cancer case series was used to compare the results of the affinity propagation with the results obtained with standard algorithms and indexes for the optimal choice of the number of clusters. Results from affinity propagation are consistent with the results already obtained having the advantage of providing an indication about the number of clusters

A novel three-colour fluorescence in situ hybridization approach for the detection of t(7;12)(q36;p13) in acute myeloid leukaemia reveals new cryptic three way translocation t(7;12;16)

© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20–30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting

Thermal adaptability of Kluyveromyces marxianus in recombinant protein production

Background: Kluyveromyces marxianus combines the ease of genetic manipulation and fermentation with the ability to efficiently secrete high molecular weight proteins, performing eukaryotic post-translational modifications. It is able to grow efficiently in a wide range of temperatures. The secretion performances were analyzed in the host K. marxianus L3 in the range between 5\ub0C and 40\ub0C by means of 3 different reporter proteins, since temperature appears a key parameter for production and secretion of recombinant proteins.Results: The recombinant strains were able to grow up to 40\ub0C and, along the tested temperature interval (5-40\ub0C), the specific growth rates (\u3bc) were generally lower as compared to those of the untransformed strain. Biomass yields were slightly affected by temperature, with the highest values reached at 15\ub0C and 30\ub0C. The secretion of the endogenous \u3b2-fructofuranosidase, used as an internal control, was efficient in the range of the tested temperature, as evaluated by assaying the enzyme activity in the culture supernatants. The endogenous \u3b2-fructofuranosidase production was temperature dependent, with the highest yield at 30\ub0C. The heterologous proteins HSA, GAA and Sod1p were all successfully produced and secreted between 5\ub0C and 40\ub0C, albeit each one presented a different optimal production temperature (15, 40, 5-30\ub0C for HSA, GAA and Sod1p, respectively).Conclusions: K. marxianus L3 has been identified as a promising and flexible cell factory. In a sole host, the optimization of growth temperatures for the efficient secretion of each individual protein can be carried out over a wide range of temperatures

Unraveling the response of plant cells to cytotoxic saponins: role of metallothionein and nitric oxide

A wide range of pharmacological properties are ascribed to natural saponins, in addition to their biological activities against herbivores, plant soilborne pathogens and pests. As for animal cells, the cytotoxicity and the chemopreventive role of saponins are mediated by a complex network of signal transduction pathways which include reactive oxygen species (ROS) and nitric oxide (NO). The involvement of other relevant components of the saponin-related signaling routes, such as the Tumor Necrosis Factor (TNF)α, the interleukin (IL)-6 and the Nuclear Transcription FactorκB (NFκB), has been highlighted in animal cells. By contrast, information concerning the response of plant cells to saponins and the related signal transduction pathways is almost missing. To date, there are only a few common features which link plant and animal cells in their response to saponins, such as the early burst in ROS and NO production and the induction of metallothioneins (MTs), small cysteine-rich, metal-binding proteins. This aspect is discussed in the present paper in view of the recent hypothesis that MTs and NO are part of a novel signal transduction pathway participating in the cell response to oxidative stress

PHOX2A and PHOX2B are differentially regulated during retinoic acid-driven differentiation of SK-N-BE(2)C neuroblastoma cell line

AbstractPHOX2B and its paralogue gene PHOX2A are two homeodomain proteins in the network regulating the development of autonomic ganglia that have been associated with the pathogenesis of neuroblastoma (NB), because of their over-expression in different NB cell lines and tumour samples. We used the SK-N-BE(2)C cell line to show that all-trans retinoic acid (ATRA), a drug that is widely used to inhibit growth and induce differentiation in NBs, regulates both PHOX2A and PHOX2B expression, albeit by means of different mechanisms: it up-regulates PHOX2A and down-regulates PHOX2B. Both mechanisms act at transcriptional level, but prolonged ATRA treatment selectively degrades the PHOX2A protein, whereas the corresponding mRNA remains up-regulated. Further, we show that PHOX2A is capable of modulating PHOX2B expression, but this mechanism is not involved in the PHOX2B down-regulation induced by retinoic acid. Our findings demonstrate that PHOX2A expression is finely controlled during retinoic acid differentiation and this, together with PHOX2B down-regulation, reinforces the idea that they may be useful biomarkers for NB staging, prognosis and treatment decision making

Angiogenesis in potentially malignant lesions and carcinomas during experimental oral carcinogenesis: a preliminary study in the hamster cheek pouch

AIM: To evaluate vascular morphology and density, angiogenic switch activation, vascular endothelial growth factor (VEGF) expression, and endothelial cell (EC) proliferation in the hamster cheek pouch (HCP) model of oral cancer. MATERIALS AND METHODS: Immunohistochemical detection of factor VIII, 5'-Bromo-2'-Deoxyuridine (BrdU) and VEGF was performed in pre-malignant and tumoral tissues. RESULTS: Activation of angiogenesis was detected adjacent to epithelial dysplasia. Vascularized area and perimeter (p<0.001) increased in dysplasias and tumors. Tumor blood vessels exhibited an enhanced vascular compression (p<0.001) and structural alterations. EC proliferation was similar in dysplasias and carcinomas. An increase in vascular density, EC proliferation and VEGF expression was found in potentially malignant tissues but not in carcinomas. CONCLUSION: The angiogenic switch occurs in the dysplastic stage preceding tumor development in the HCP model of oral cancer. In potentially malignant tissues, increased VEGF expression favors EC proliferation and an increase in vascular density. Conversely, in tumors, VEGF is no longer of pivotal importance.Fil: Aromando, Romina F.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Raimondi, Ana Rosa. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pérez, Miguel A.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Trivillin, Verónica Andrea. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Itoiz, Maria Elina. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Amyloid detection and typing yield of skin biopsy in systemic amyloidosis and polyneuropathy.

OBJECTIVE Disease-modifying therapies are available for amyloidosis but are ineffective if end-organ damage is severe. As small fiber neuropathy is an early and common feature of amyloidosis, we assessed detection and typing yield of skin biopsy for amyloid in patients with confirmed systemic amyloidosis and neuropathic symptoms. METHODS In this case-control study, patients with transthyretin and light chain amyloidosis (ATTRv, ATTRwt, and AL) were consecutively recruited. They were sex and age-matched to three control groups (1) non-neuropathic controls (NNC), (2) monoclonal gammopathy of undetermined significance (MGUS), and (3) other neuropathic disease controls (ONC). Patients underwent a double 3 mm skin biopsy in proximal and distal leg. Amyloid index and burden, protein typing by immuno-electron microscopy, intraepidermal nerve fiber density, electroneuromyography, and clinical characteristics were analyzed. RESULTS We studied 15 subjects with confirmed systemic amyloidosis, 20 NNC, 18 MGUS, and 20 ONC. Amyloid was detected in 100% of patients with amyloidosis (87% in ankle and 73% in thigh). It was not detected in any of the control groups. A small fiber neuropathy was encountered in 100% of amyloidosis patients, in 80% of MGUS, and in 78% of ONC. Amyloid burden was higher in ATTRv, followed by AL and ATTRwt. The ultrastructural examination allowed the identification of the precursor protein by immunotyping in most of the cases. INTERPRETATION Skin biopsy is a minimally invasive test with optimal sensitivity for amyloid. It allows amyloid typing by electron microscope to identify the precursor protein. The diagnostic work up of systemic amyloidosis should include a skin biopsy