108 research outputs found

    The yin-yang relationship between essentialist and non-essentialist discourses related to the participation of children of migrants, and its implication for how to research

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    There is a complex relationship between the essentialist and non-essentialist discourses that respectively fail to and succeed in recognising the potential for participation which the children of migrants bring with them into new cultural settings. These competing discourses curl around each other within the structures of educational settings and within all the people involved including the children themselves. A yin-yang framework helps us to see the nature of this entwined relationship and the hybridity which is the key to untangling it. It helps researchers to understand that getting to the bottom of what is going on is not straightforward and requires that they reassess who they are and how they should proceed. Sometimes it takes unusual and unexpected circumstances, such as those brought about by the emergency of the COVID-19 pandemic to shake their thinking-as-usual and to see the unexpected

    Block and thread intercultural narratives and positioning: conversations with newly arrived postgraduate students

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    This paper considers how, in the process of positioning that is implicit in every interaction, all of us employ multiple and often competing narratives when we talk about cultural identity and our relationships with new cultural environments. In interviews with newly arrived postgraduate students about their experience of travelling to study abroad, the students employ competing block and thread narratives. Block narratives represent an essentialist discourse of culture. As such, they are easily converted into cultural prejudice by blocking the possibility for understanding and sharing at the point of tolerating an Other who can never be like ‘us’. These are default narratives because of the way in which we are brought up in our societies within a global positioning and politics. Thread narratives instead support a critical cosmopolitan discourse of cultural travel and shared meanings across structural boundaries that act against cultural prejudice. Threads need to be nurtured as alternative forms of engagement. Therefore, there is a place for the researchers to intervene with their own thread narratives. This intervention is both allowed within and supported by an understanding that researchers join with their participants in the creative intercultural events of the interview

    ‘I already have a culture.’ Negotiating competing grand and personal narratives in interview conversations with new study abroad arrivals

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    In an interview with a postgraduate student about her intercultural experience of recently arriving for study abroad, it was found that the two researchers and the student were engaged in a mutual exploration of cultural identity. The in- terview events became conversational and took the form of small culture formation on the go in which each participant employed diverse narratives to project, make sense of and negotiate expression of cultural identity. The stu- dent shifted between personal narratives drawn from her particular cultural trajectories and splintered from grand narratives of nation and global position- ing, between non- essentialist threads and essentialist blocks. The researchers learned from her and intervened to facilitate shifts to non-essentialist threads, drawing on narratives from their own personal cultural trajectories, but some- times also falling into essentialist blocks splintered from grand narratives. The roles of ideology and competing essentialist and non-essentialist discourses of culture were implicit in these negotiations, as were the personal agency of the student as she responded to the constraining conflicts, structures and hierarchies encountered through the events she spoke about. Rather than providing a picture of intercultural assimilation and integration, interculturality is revealed as a hesitant and searching negotiation, sometimes of vulnerability, wrong-footedness and occasional assault on identity

    Pulmonary thromboembolism secondary to pelvic thrombosis related to giant ovarian tumor

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    Pulmonary thromboembolism (PTE) is one of the major complications in oncologic patients. The incidence of PTE in these cases is 4 to 7 times higher than in non-oncologic patients. Ovarian tumors, specifically those of large sizes, may impair the blood flow through the pelvic veins as tumor pressure over the pelvic vessels increases the incidence of thrombosis. The authors report the case of the unexpected death of a 74-year-old female due to massive pulmonary thromboembolism, associated with an ovarian tumor almost of 15 kg of weight that filled the abdominal and pelvic cavities. The compressive effect on the walls of the pudendal and periuterine veins somehow facilitated the local thrombosis. According to the histological characterization on post-mortem samples, the mass was identified as an \u201catypical proliferative (borderline) mucinous tumor.\u201d The case emphasizes the important association between pulmonary thromboembolism and ovarian tumors

    Applying an Empirical Hydropathic Forcefield in Refinement May Improve Low-Resolution Protein X-Ray Crystal Structures

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    BACKGROUND: The quality of X-ray crystallographic models for biomacromolecules refined from data obtained at high-resolution is assured by the data itself. However, at low-resolution, >3.0 Å, additional information is supplied by a forcefield coupled with an associated refinement protocol. These resulting structures are often of lower quality and thus unsuitable for downstream activities like structure-based drug discovery. METHODOLOGY: An X-ray crystallography refinement protocol that enhances standard methodology by incorporating energy terms from the HINT (Hydropathic INTeractions) empirical forcefield is described. This protocol was tested by refining synthetic low-resolution structural data derived from 25 diverse high-resolution structures, and referencing the resulting models to these structures. The models were also evaluated with global structural quality metrics, e.g., Ramachandran score and MolProbity clashscore. Three additional structures, for which only low-resolution data are available, were also re-refined with this methodology. RESULTS: The enhanced refinement protocol is most beneficial for reflection data at resolutions of 3.0 Å or worse. At the low-resolution limit, ≥4.0 Å, the new protocol generated models with Cα positions that have RMSDs that are 0.18 Å more similar to the reference high-resolution structure, Ramachandran scores improved by 13%, and clashscores improved by 51%, all in comparison to models generated with the standard refinement protocol. The hydropathic forcefield terms are at least as effective as Coulombic electrostatic terms in maintaining polar interaction networks, and significantly more effective in maintaining hydrophobic networks, as synthetic resolution is decremented. Even at resolutions ≥4.0 Å, these latter networks are generally native-like, as measured with a hydropathic interactions scoring tool

    Bound Water at Protein-Protein Interfaces: Partners, Roles and Hydrophobic Bubbles as a Conserved Motif

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    Background There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region. Methodology A data set of 4741 water molecules abstracted from 179 high-resolution (≤ 2.30 Å) X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed Relevance was used to classify the general roles of the water molecules. Results The water molecules were found to be involved in: a) (bridging) interactions with both proteins (21%), b) favorable interactions with only one protein (53%), and c) no interactions with either protein (26%). This trend is shown to be independent of the crystallographic resolution. Interactions with residue backbones are consistent for all classes and account for 21.5% of all interactions. Interactions with polar residues are significantly more common for the first group and interactions with non-polar residues dominate the last group. Waters interacting with both proteins stabilize on average the proteins\u27 interaction (−0.46 kcal mol−1), but the overall average contribution of a single water to the protein-protein interaction energy is unfavorable (+0.03 kcal mol−1). Analysis of the waters without favorable interactions with either protein suggests that this is a conserved phenomenon: 42% of these waters have SASA ≤ 10 Å2 and are thus largely buried, and 69% of these are within predominantly hydrophobic environments or “hydrophobic bubbles”. Such water molecules may have an important biological purpose in mediating protein-protein interactions

    Semiquantitative Analysis of Clinical Heat Stress in Clostridium difficile Strain 630 Using a GeLC/MS Workflow with emPAI Quantitation.

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    <div><p><i>Clostridium difficile</i> is considered to be the most frequent cause of infectious bacterial diarrhoea in hospitals worldwide yet its adaptive ability remains relatively uncharacterised. Here, we used GeLC/MS and the exponentially modified protein abundance index (emPAI) calculation to determine proteomic changes in response to a clinically relevant heat stress. Reproducibility between both biological and technical replicates was good, and a 37°C proteome of 224 proteins was complemented by a 41°C proteome of 202 proteins at a 1% false discovery rate. Overall, 236 <i>C. difficile</i> proteins were identified and functionally categorised, of which 178 were available for comparative purposes. A total of 65 proteins (37%) were modulated by 1.5-fold or more at 41°C compared to 37°C and we noted changes in the majority of proteins associated with amino acid metabolism, including upregulation of the reductive branch of the leucine fermentation pathway. Motility was reduced at 41°C as evidenced by a 2.7 fold decrease in the flagellar filament protein, FliC, and a global increase in proteins associated with detoxification and adaptation to atypical conditions was observed, concomitant with decreases in proteins mediating transcriptional elongation and the initiation of protein synthesis. Trigger factor was down regulated by almost 5-fold. We propose that under heat stress, titration of the GroESL and dnaJK/grpE chaperones by misfolded proteins will, in the absence of trigger factor, prevent nascent chains from emerging efficiently from the ribosome causing translational stalling and also an increase in secretion. The current work has thus allowed development of a heat stress model for the key cellular processes of protein folding and export.</p></div

    A Medicinal Chemist’s Guide to Molecular Interactions

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    Isozyme-Specific Ligands for O-acetylserine sulfhydrylase, a Novel Antibiotic Target

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    Conceived and designed the experiments: FS PC BC ES AM. Performed the experiments: FS RS ES PF SR. Analyzed the data: FS BC ES PF GEK PFC AM. Contributed reagents/materials/analysis tools: PC PB GC. Wrote the paper: FS GEK BC AM.The last step of cysteine biosynthesis in bacteria and plants is catalyzed by O-acetylserine sulfhydrylase. In bacteria, two isozymes, O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, have been identified that share similar binding sites, although the respective specific functions are still debated. O-acetylserine sulfhydrylase plays a key role in the adaptation of bacteria to the host environment, in the defense mechanisms to oxidative stress and in antibiotic resistance. Because mammals synthesize cysteine from methionine and lack O-acetylserine sulfhydrylase, the enzyme is a potential target for antimicrobials. With this aim, we first identified potential inhibitors of the two isozymes via a ligand- and structure-based in silico screening of a subset of the ZINC library using FLAP. The binding affinities of the most promising candidates were measured in vitro on purified O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B from Salmonella typhimurium by a direct method that exploits the change in the cofactor fluorescence. Two molecules were identified with dissociation constants of 3.7 and 33 µM for O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, respectively. Because GRID analysis of the two isoenzymes indicates the presence of a few common pharmacophoric features, cross binding titrations were carried out. It was found that the best binder for O-acetylserine sulfhydrylase-B exhibits a dissociation constant of 29 µM for O-acetylserine sulfhydrylase-A, thus displaying a limited selectivity, whereas the best binder for O-acetylserine sulfhydrylase-A exhibits a dissociation constant of 50 µM for O-acetylserine sulfhydrylase-B and is thus 8-fold selective towards the former isozyme. Therefore, isoform-specific and isoform-independent ligands allow to either selectively target the isozyme that predominantly supports bacteria during infection and long-term survival or to completely block bacterial cysteine biosynthesis.Yeshttp://www.plosone.org/static/editorial#pee

    The child as a medium. Breakdown and possible resurgence of children's agency in the era of pandemic

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    This paper deals with the unpredictable outbreak of the pandemic, explaining its impact on the education system, and with structural flexibility as a way to face unpredictability, based on the generalisability and coordination of manifestations of agency. The pandemic has enhanced a narrative of the child as a medium of learning, which undermines children's agency. The example of the research project CHILD-UP (Children Hybrid Integration: Learning Dialogue as a way of Upgrading policies of Participation) is used to show how children's agency and structural flexibility in classroom interactions can be supported and analysed
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