672 research outputs found

    Exploring the Resilience of Heartbroken Divorced Individuals at a University in London

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    This study explored how resilience was achieved and experienced among individuals who experienced heartbreak from divorce. If individuals experience resilience, the study will further explore how resilience was achieved. A sample of (n = 10) participants aged between 42 and 61 years underwent hour-long online interviews. Participants answered a series of open-ended questions, explaining their experiences of divorce and heartbreak. Through a qualitative thematic analysis, three main themes were identified: mental health, support of others, and positive and negative activities. There were noticeably high levels of common responses from shared experiences of the divorce process and how resilience was achieved. Results of the study found that while heartbreak and poor mental health conditions arise from divorce, overcoming them resiliently was achievable through positive activities and social support

    New synchronization method for <i>Plasmodium falciparum</i>

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    &lt;b&gt;Background&lt;/b&gt;: Plasmodium falciparum is usually asynchronous during in vitro culture. Although various synchronization methods are available, they are not able to narrow the range of ages of parasites. A newly developed method is described that allows synchronization of parasites to produce cultures with an age range as low as 30 minutes. &lt;b&gt;Methods&lt;/b&gt;: Trophozoites and schizonts are enriched using Plasmion. The enriched late stage parasites are immobilized as a monolayer onto plastic Petri dishes using concanavalin A. Uninfected erythrocytes are placed onto the monolayer for a limited time period, during which time schizonts on the monolayer rupture and the released merozoites invade the fresh erythrocytes. The overlay is then taken off into a culture flask, resulting in a highly synchronized population of parasites. &lt;b&gt;Results&lt;/b&gt;: Plasmion treatment results in a 10- to 13-fold enrichment of late stage parasites. The monolayer method results in highly synchronized cultures of parasites where invasion has occurred within a very limited time window, which can be as low as 30 minutes. The method is simple, requiring no specialized equipment and relatively cheap reagents. &lt;b&gt;Conclusions&lt;/b&gt;: The new method for parasite synchronization results in highly synchronized populations of parasites, which will be useful for studies of the parasite asexual cell cycle

    PNAS plus: plasmodium falciparum responds to amino acid starvation by entering into a hibernatory state

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    The human malaria parasite Plasmodium falciparum is auxotrophic for most amino acids. Its amino acid needs are met largely through the degradation of host erythrocyte hemoglobin; however the parasite must acquire isoleucine exogenously, because this amino acid is not present in adult human hemoglobin. We report that when isoleucine is withdrawn from the culture medium of intraerythrocytic P. falciparum, the parasite slows its metabolism and progresses through its developmental cycle at a reduced rate. Isoleucine-starved parasites remain viable for 72 h and resume rapid growth upon resupplementation. Protein degradation during starvation is important for maintenance of this hibernatory state. Microarray analysis of starved parasites revealed a 60% decrease in the rate of progression through the normal transcriptional program but no other apparent stress response. Plasmodium parasites do not possess a TOR nutrient-sensing pathway and have only a rudimentary amino acid starvation-sensing eukaryotic initiation factor 2α (eIF2α) stress response. Isoleucine deprivation results in GCN2-mediated phosphorylation of eIF2α, but kinase-knockout clones still are able to hibernate and recover, indicating that this pathway does not directly promote survival during isoleucine starvation. We conclude that P. falciparum, in the absence of canonical eukaryotic nutrient stress-response pathways, can cope with an inconsistent bloodstream amino acid supply by hibernating and waiting for more nutrient to be provided

    RANK/RANKL/OPG pathway: genetic associations with stress fracture period prevalence in elite athletes

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    Context: The RANK/RANKL/OPG signalling pathway is important in the regulation of bone turnover, with single nucleotide polymorphisms (SNPs) in genes within this pathway associated with bone phenotypic adaptations. Objective: To determine whether four SNPs associated with genes in the RANK/RANKL/OPG signalling pathway were associated with stress fracture injury in elite athletes. Design, Participants, and Methods: Radiologically confirmed stress fracture history was reported in 518 elite athletes, forming the Stress Fracture Elite Athlete (SFEA) cohort. Data were analysed for the whole group, and were sub-stratified into male and cases of multiple stress fracture group. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays. Results: SNPs rs3018362 (RANK) and rs1021188 (RANKL) were associated with stress fracture injury (p<0.05). 8.1% of stress fracture group and 2.8% of the non-stress fracture group were homozygote for the rare allele of rs1021188. Allele frequency, heterozygotes and homozygotes for the rare allele of rs3018362 were associated with stress fracture period prevalence (p<0.05). Analysis of the male only group showed 8.2% of rs1021188 rare allele homozygotes to have suffered a stress fracture while 2.5% of the non-stress fracture group were homozygous. In cases of multiple stress fractures, homozygotes for the rare allele of rs1021188, and individuals possessing at least one copy of the rare allele of rs4355801 (OPG) were shown to be associated with stress fracture injury (p<0.05). Conclusions: The data support an association between SNPs in the RANK/RANKL/OPG signalling pathway and the development of stress fracture injury. The association of rs3018362 (RANK) and rs1021188 (RANKL) with stress fracture injury susceptibility supports their role in the maintenance of bone health, and offers potential targets for therapeutic interventions

    Impacting student anxiety for the USMLE Step 1 through process-oriented preparation

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    Background: Standardized examinations are the key components of medical education. The USMLE Step 1 is the first of these important milestones. Success on this examination requires both content competency and efficient strategies for study and review. Students employ a wide variety of techniques in studying for this examination, with heavy reliance on personal study habits and advice from other students. Nevertheless, few medical curricula formally address these strategies. Methods: In response to student-generated critique at our institution, a five-part seminar series on process-oriented preparation was developed and implemented to address such concerns. The series focused on early guidance and preparation strategies for Step 1 and the many other important challenges in medical school. Emphasis was placed on facilitating conversation and mentorship opportunities between students. Results &amp; Conclusions: A profoundly positive experience was reported by our medical students that included a decreased anxiety level for the Step 1 examination

    Capturing the lived experience of immigrant entrepreneurs: case studies from the ELIE project

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    ELIE stands for Employability: Learning from International Entrepreneurship and is an European Union Erasmus funded project. Our aim is to capture the lived experiences of immigrant entrepreneurs in order to develop learning materials for potential entrepreneurs and students and to advise policy makers and regulators on how best to support entrepreneurs. This report contain 40 case studies collated from 200 interviews conducted in four EU countries, the UK, Greece, Finland and Poland, amongst immigrant entrepreneurs. The interviews showed a remarkable level of common experience across all four countries, and as a result we have been able to develop a taxonomy of routes into entrepreneurship and typologies of entrepreneurship that have been used as an organizing structure within this report. We believe this report will be of use to others researching and working in the area of of international entrepreneurship

    The status of epidermal growth factor receptor in borderline ovarian tumours

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    The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p<0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p=0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear localization similarities between BOTs and LGSCs and not HGSCs support the hypothesis suggesting evolution of LGSCs from BOTs. We also confirm that EGFR mutations and amplifications are not molecular events in the pathogenesis of BOTs

    Knockout studies reveal an important role of <i>plasmodium</i> lipoic acid protein ligase a1 for asexual blood stage parasite survival

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    Lipoic acid (LA) is a dithiol-containing cofactor that is essential for the function of a-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl): &lt;i&gt;N&lt;/i&gt;-octanoyl (lipoyl) transferase (LipB) or lipoic acid protein ligases (LplA). Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that &lt;i&gt;LplA1&lt;/i&gt; plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite &lt;i&gt;P.falciparum&lt;/i&gt; consistently were unsuccessful while in the rodent malaria model parasite &lt;i&gt;P. berghei&lt;/i&gt; the &lt;i&gt;LplA1&lt;/i&gt; gene locus was targeted by knock-in and knockout constructs. However, the &lt;i&gt;LplA1&lt;/i&gt; &lt;sup&gt;(-)&lt;/sup&gt; mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite

    Embodied cognitive ecosophy: the relationship of mind, body, meaning and ecology

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    The concept of embodied cognition has had a major impact in a number of disciplines. The extent of its consequences on general knowledge and epistemology are still being explored. Embodied cognition in human geography has its own traditions and discourses but these have become somewhat isolated in the discipline itself. This paper argues that findings in other disciplines are of value in reconceptualising embodied cognition in human geography and this is explored by reconsidering the concept of ecosophy. Criticisms of ecosophy as a theory are considered and recent work in embodied cognition is applied to consider how such criticisms might be addressed. An updated conceptualisation is proposed, the embodied cognitive ecosophy, and three characteristics arising from this criticism and synthesis are presented with a view to inform future discussions of ecosophy and emotional geography
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