β2-m amyloid fibrils are endocytosed into endosomes/lysosomes, leading to the disruption of their membranes.

<p>Representative electron micrographs of HIG-82 cells taken as described in Materials and Methods. HIG-82 cells were incubated with Ham’s F12 medium containing vehicle buffer for 6 hrs (A), or 100 μg/ml β2-m fibrils for 2 hrs (B, C) or 6 hrs (D-F) as described in Materials and Methods. The inset in (B) is a higher magnification of the box. (B, D) HIG-82 cells were covered with amyloid fibrils. Note that a part of the plasma membrane invaginated and fused to form an endocytic vesicle containing amyloid fibrils (inset in B). (C, E) Many endosomes/lysosomes were filled with amyloid fibrils, and some endosomal/lysosomal membranes were disrupted by intravesicular fibrils. (F) Nuclear deformation, shrinkage, and chromatin condensation at the nuclear rim were also observed. The scale bars are 5 μm long in A, B, D and F and 1 μm long in C and E.</p

Endocytosed β2-m amyloid fibrils leak from endosomes/lysosomes into the cytosol.

<p>Representative electron micrographs of HIG-82 cells incubated with Ham’s F12 medium containing 100 μg/ml β2-m fibrils for 6 hrs as described in Materials and Methods. Images were taken as described in Materials and Methods. (D-F) Higher magnifications of the boxes in A-C, respectively. Note that the endocytosed amyloid fibrils leaked from endosomal/lysosomal vesicles into the cytosol (A, D), and some fibrils were found adjacent to mitochondria (B, C, E, F). The scale bars are 500 nm long in A-C and 200 nm long in D-F.</p

β2-m amyloid fibrils are internalized and sorted to lysosomes.

<p>HIG-82 cells incubated with Ham’s F12 medium containing vehicle buffer, 10 μg/ml β2-m monomer, or 10 μg/ml β2-m fibrils for 12 hrs were stained for lysosomes (red), β2-m (green), and nuclei (blue), and observed with the confocal laser microscope as described in Materials and Methods. When the cells were incubated with fibrils (right column), green fluorescence indicating β2-m fibrils were observed inside the cells in a granular pattern, as well as on the surface of the cells. Importantly, some green-colored granules containing β2-m fibrils were merged with red-colored lysosomes. The scale bars are 10 μm long.</p

β2-m amyloid fibrils induce apoptosis of HIG-82 cells as measured by the TUNEL assay.

<p>After HIG-82 cells were incubated with Ham’s F12 medium containing vehicle buffer or 100 μg/ml β2-m fibrils or r-β2-m monomer for 2 days, TUNEL assay was performed as described in Materials and Methods. (A) The representative fluorescence images of TUNEL and DAPI double staining. The original magnification was x100. (B) The percentage of apoptotic cells to total cells. Data were presented as a dot plot of the ratios of five independent experiments with the mean value. Statistical analysis was performed by Mann-Whitney U-test. *P < 0.05.</p

β2-m amyloid fibrils have no effect on artificial plasma membranes.

<p>(A) A representative light micrograph of large unilamellar vesicles (LUVs) containing carboxyfluorescein prepared as described in Materials and Methods. They were less than 50 μm in diameter. The scale bars are 50 μm long. After LUVs were incubated with β2-m fibrils or r-β2-m monomer (final 0 or 100 μg/ml), or Triton X-100 as a positive control (final 2%) for 15 min (B) or 1 day (C), the fluorescence was measured as described in Materials and Methods. (B, C) β2-m amyloid fibrils did not significantly destruct artificial plasma membranes of LUVs. Statistical analysis was performed by Student’s unpaired t-test. *P < 0.05 vs. positive control.</p

Standing on their own two feet. The role of nursing education in the life stories of nurse teachers from Bangladesh

[eng] The nursing profession in Bangladesh has undergone substantial development over recent decades but still faces significant challenges. A remarkable gap has been described between the institutionally-accepted image of nursing as the provision of hands-on care and the small amount of time that nurses allocate to it, especially in government hospitals. The reasons for this contradiction have shown a complex interaction between historical, socioeconomic and cultural factors. These are mainly related to the conflict between the British-inherited curriculum, with a strong emphasis on basic care activities, social and gender norms, and longstanding discrimination against nurses in their institutional settings and society. This research aims to provide a theoretical analysis of the ways in which structural factors intersect with the professional and social experiences of a group of nurse teachers. The objectives of the thesis are to describe nurses’ views about nursing care and their profession, to discuss to what extent nursing education has been an empowering tool, and to analyse how the nurses’ socioeconomic background, personal experiences and life events have influenced their professional careers and their conceptualisation of nursing and care. A critical phenomenological analysis of the nurses’ life stories has been used, relating the stories to the broader history and political economy of nursing in Bangladesh. Twenty-two nurses were selected and interviewed over an eight-month fieldwork period, of which seven were selected as key informants. The discussion is mainly based on theoretical contributions from anthropology, practice theory, feminism and a critical analysis of nursing knowledge. A common rhetoric was found among the nurses: namely that nursing care has ‘deteriorated’. They tended to emphasise hands-on care and the ‘old’ apprenticeship model, while also approving moves towards a more professional model. Nursing care activities were understood as a mixture of service and management of the wards and patients, linked to a wish to ‘utilise’ the knowledge that they were continuously acquiring. Therefore, nursing education was broadly empowering in terms of knowledge, independence, and self-realization. Nevertheless, at some moments social and institutional discrimination made the m feel disempowered, frustrated and vulnerable. Even so, the nurses interviewed have achieved successful professional careers, together with a significant amount of social recognition. Without ignoring their outstanding individual capacities, the role that key people and institutions had in supporting them in their eagerness to learn has to be considered. Finally, the act of caring itself and the knowledge that it produces may also be a source of personal and collective agency. However, work is needed in order to create and maintain the necessary conditions for the caring experience to be empowering. This responsibility falls beyond the nursing field, as it involves structural changes, especially in terms of gender and class inequalities.[cat] La professió infermera a Bangladesh ha experimentat importants avenços en les últimes dècades, tot i que encara presenta reptes considerables. La imatge institucionalment acceptada de la infermeria com la provisió de cures i contacte continuat amb els pacients contrasta amb la poca dedicació de moltes infermeres a aquestes activitats, especialment en els hospitals públics. Aquesta contradicció s’explica per una complexa interacció entre factors històrics, socioeconòmics i culturals. Existeix un conflicte entre un pla d’estudis heretat de l’època colonial Britànica, amb un fort èmfasi en les activitats de cures bàsiques, les normes socials i de gènere, i la històrica discriminació de les infermeres en els seus entorns institucionals i socials. Aquesta tesi pretén teoritzar sobre les formes en què els factors estructurals s’interseccionen amb les experiències professionals i socials d’un grup de professores d’infermeria. Els objectius de la tesi són: descriure les visions de les infermeres sobre el concepte de cura i sobre la seva professió; discutir fins a quin punt l’educació en infermeria ha estat una eina empoderadora, i analitzar de quina manera el context socioeconòmic, experiències personals i esdeveniments vitals de les professores han influït en la seva carrera professional i en la seva conceptualització de les cures infermeres. La recerca ha realitzat una anàlisi fenomenològica crítica de les històries de vida de les professores d’infermeria, relacionant-les amb la història i economia política de la infermeria a Bangladesh. Vint infermeres van ser entrevistades durant un període de vuit mesos, entre les quals set professores van ser escollides com a informants clau. La discussió es basa principalment en les aportacions teòriques de l'antropologia, la teoria de la pràctica, el feminisme i l’anàlisi crítica del coneixement infermer. Les infermeres entrevistades sostenien, en general, que les cures d'infermeria s’havien ‘deteriorat’. Les seves narratives tendien a emfatitzar el ‘vell’ model d’aprenentatge pràctic, alhora que es valorava l’evolució cap a un model més professional. Les infermeres conceptualitzaven la cura com una barreja entre les nocions de servei i de gestió de les sales i dels pacients, juntament amb un desig d’utilitzar els coneixements que constantment adquiriren. Per tant, l’educació en infermeria ha estat en general empoderadora quant a coneixements, independència i sentit d’auto-realització. Tot i així, en certs moments, la discriminació social i institucional viscuda, els va fer sentir impotents, frustrades i vulnerables. Malgrat les dificultats, però, les infermeres d’aquesta tesi han aconseguit un exitós desenvolupament professional, així com un grau de reconeixement social considerable. Sense ignorar les seves notables capacitats individuals, cal considerar també el suport rebut per part de diferents persones i institucions en el seu constant desig de formar-se i aprendre. Finalment, l’acte de tenir cura i el coneixement que se’n deriva, són en si mateixos una font d’agència personal i col·lectiva. No obstant això, cal treballar per crear i mantenir les condicions necessàries perquè l’experiència cura sigui empoderadora. Aquesta és una responsabilitat que excedeix l’àmbit infermer, ja que implica canvis estructurals, especialment en relació a les desigualtats de gènere i classe

Supersaturation-Limited and Unlimited Phase Spaces Compete to Produce Maximal Amyloid Fibrillation near the Critical Micelle Concentration of Sodium Dodecyl Sulfate

Although various natural and synthetic compounds have been shown to accelerate or inhibit the formation of amyloid fibrils, the mechanisms by which they achieve these adverse effects in a concentration-dependent manner currently remain unclear. Sodium dodecyl sulfate (SDS), one of the compounds that has adverse effects on fibrillation, is the most intensively studied. Here we examined the effects of a series of detergents including SDS on the amyloid fibrillation of β₂-microglobulin at pH 7.0, a protein responsible for dialysis-related amyloidosis. In all the detergents examined (i.e., SDS, sodium decyl sulfate, sodium octyl sulfate, and sodium deoxycholate), amyloid fibrillation was accelerated and inhibited at concentrations near the critical micelle concentration (CMC) and higher than CMC, respectively. The most stable conformation changed from monomers with a β-structure to amyloid fibrils with a β-structure and then to α-helical complexes with micelles with an increase in detergent concentrations. These results suggest that competition between supersaturation-limited fibrillation and unlimited mixed micelle formation between proteins and micelles underlies the detergent concentration-dependent complexity of amyloid fibrillation

Additional file 1: of Newly recognized cerebral infarctions on postmortem imaging: a report of three cases with systemic infectious disease

Timeline of Case 1. (DOCX 20 kb