Practical Linked Data: Learning How to Create and Use Linked Data in the Real World

Want to learn more about linked data? This session is intended for anyone interested in learning more about linked data, whether they are new to the subject or more advanced. We will begin by describing what linked data is. We then discuss our specific project and how we created linked data using the MCTC zine collection, the Anchor Archive Zine Thesaurus, the Open Metadata Registry and Open Refine. After that, we talk about what our group might do next, what we learned from the project, and show some other examples of projects that use linked data

Post‐traumatic growth in prisoners and its association with the quality of staff–prisoner relationships

Background: Being sentenced to prison can be a traumatic experience for many people that leads to negative effects, including reoffending or disorders of mental health. Emerging research, however, has suggested that traumatic events can at times also lead to posttraumatic growth, leading us to question whether it is possible that prisoners could experience posttraumatic growth. Aims: Our aims were to explore the prevalence of posttraumatic growth in prisoners, and the association between posttraumatic growth and prisoners’ perceptions of the quality of their relationships with staff members. Our primary hypothesis was that there would be a positive association between perceptions of the quality of relationships with staff members and posttraumatic growth. We also hypothesised an interaction between staff-prisoner relationships and the extent to which sentencing was experienced as traumatic. Method: The Posttraumatic Growth Inventory (PGI) and the Barrett-Lennard Relationship Inventory were distributed to all 762 prisoners in a high-security adult male prison in England. One-tailed correlations were used to test for associations between variables. A hierarchical regression analysis was conducted to test for an interaction between staff-prisoner relationship ratings, trauma of sentencing and posttraumatic growth. Results: Just over one fifth of the men (n = 160) returned questionnaires. 76 (48%) had scores indicative of moderate-to-high posttraumatic growth. There was a significant positive association between the perceptions of the relationships with staff members and the posttraumatic growth reported. There was no significant interaction between the staff-prisoner relationships and the experienced trauma of imprisonment. Conclusions and implications for clinical practice: The current study extends the prisoner based literature through finding that higher perceived levels of posttraumatic growth were associated with experiencing empathy, positive regard, acceptance and genuineness from prison staff. The findings highlight the need for quality relationships to be adopted in all aspects of the prison setting and culture. Future applied research into these relationship-based factors and their role in promoting positive psychological outcomes in prisoners is needed

Mitochondrial Mislocalization Underlies Aβ42-Induced Neuronal Dysfunction in a Drosophila Model of Alzheimer's Disease

The amyloid-β 42 (Aβ42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Aβ42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Aβ42 induces mitochondrial mislocalization, which contributes to Aβ42-induced neuronal dysfunction in a transgenic Drosophila model. In the Aβ42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. In contrast, organization of microtubule or global axonal transport was not significantly altered at this stage. Aβ42-induced behavioral defects were exacerbated by genetic reductions in mitochondrial transport, and were modulated by cAMP levels and PKA activity. Levels of putative PKA substrate phosphoproteins were reduced in the Aβ42 fly brains. Importantly, perturbations in mitochondrial transport in neurons were sufficient to disrupt PKA signaling and induce late-onset behavioral deficits, suggesting a mechanism whereby mitochondrial mislocalization contributes to Aβ42-induced neuronal dysfunction. These results demonstrate that mislocalization of mitochondria underlies the pathogenic effects of Aβ42 in vivo

Enforced expression of PPP1R13L increases tumorigenesis and invasion through p53-dependent and p53-independent mechanisms.

PPP1R13L was initially identified as a protein that binds to the NF-[kappa]B subunit p65/RelA and inhibits its transcriptional activity. It also binds p53 and inhibits its action. One set of experimental findings based on over-expression of PPP1R13L indicates that PPP1R13L blocks apoptosis. Another set of experiments, based on endogenous production of PPP1R13L, suggests that the protein may sometimes be pro-apoptotic. We have used primary mouse embryonic fibroblasts (MEFs), dually transformed by H-ras and Adenovirus E1A and differing in their p53 status, to explore the effects of PPP1R13L over-expression, thus examining the ability of PPP1R13L to act as an oncoprotein. We found that over-expression of PPP1R13L strongly accelerated tumor formation by ras/E1A and also resulted in an increased metastatic potential of the tumors. PPP1R13L over-expressing cells were depleted for both p53 and active p65/RelA and we found that both p53 dependent and independent apoptosis pathways were regulated by PPP1R13L. Finally, studies with the proteasome inhibitor MG132 revealed that over-expression of PPP1R13L causes faster p53 degradation, a likely explanation for the depletion of p53. Taken together, our results show that increased levels of PPP1R13L can increase tumorigenesis and furthermore pinpoint PPP1R13L as a gene that influences metastasis

Egulating gene expression through RNA nuclear retention

Multiple mechanisms have evolved to regulate the eukaryotic genome. We have identified CTN-RNA, a mouse tissue-specific w8 kb nuclear-retained poly(A) + RNA that regulates the level of its protein-coding partner. CTN-RNA is transcribed from the protein-coding mouse cationic amino acid transporter 2 (mCAT2) gene through alternative promoter and poly(A) site usage. CTN-RNA is diffusely distributed in nuclei and is also localized to paraspeckles. The 3�UTR of CTN-RNA contains elements for adenosine-to-inosine editing, involved in its nuclear retention. Interestingly, knockdown of CTN-RNA also downregulates mCAT2 mRNA. Under stress, CTN-RNA is posttranscriptionally cleaved to produce protein-coding mCAT2 mRNA. Our findings reveal a role of the cell nucleus in harboring RNA molecules that are not immediately needed to produce proteins but whose cytoplasmic presence is rapidly required upon physiologic stress. This mechanism of action highlights an important paradigm for the role of a nuclear-retained stable RNA transcript in regulating gene expression

Exercise, APOE, and Working Memory: MEG and Behavioral Evidence for Benefit of Exercise in Epsilon4 Carriers

Performance on the Sternberg working memory task, and MEG cortical response on a variation of the Sternberg task were examined in middle-aged carriers and non-carriers of the APOE ε4 allele. Physical activity was also assessed to examine whether exercise level modifies the relationship between APOE genotype and neurocognitive function. Regression revealed that high physical activity was associated with faster RT in the six- and eight-letter conditions of the Sternberg in ε4 carriers, but not in the non-carriers after controlling for age, gender, and education (N = 54). Furthermore, the MEG analysis revealed that sedentary ε4 carriers exhibited lower right temporal lobe activation on matching probe trials relative to high-active ε4 carriers, while physical activity did not distinguish non-carriers (N = 23). The M170 peak was identified as a potential marker for pre-clinical decline as ε4 carriers exhibited longer M170 latency, and highly physically active participants exhibited greater M170 amplitude to matching probe trials

A simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes.

Hundreds of human genes are associated with neurological diseases, but translation into tractable biological mechanisms is lagging. Larval zebrafish are an attractive model to investigate genetic contributions to neurological diseases. However, current CRISPR-Cas9 methods are difficult to apply to large genetic screens studying behavioural phenotypes. To facilitate rapid genetic screening, we developed a simple sequencing-free tool to validate gRNAs and a highly effective CRISPR-Cas9 method capable of converting >90% of injected embryos directly into F0 biallelic knockouts. We demonstrate that F0 knockouts reliably recapitulate complex mutant phenotypes, such as altered molecular rhythms of the circadian clock, escape responses to irritants, and multi-parameter day-night locomotor behaviours. The technique is sufficiently robust to knockout multiple genes in the same animal, for example to create the transparent triple knockout crystal fish for imaging. Our F0 knockout method cuts the experimental time from gene to behavioural phenotype in zebrafish from months to one week

Radiation-induced lung toxicity in non-small-cell lung cancer: Understanding the interactions of clinical factors and cytokines with the dose-toxicity relationship

BACKGROUND AND PURPOSE: Current methods to estimate risk of radiation-induced lung toxicity (RILT) rely on dosimetric parameters. We aimed to improve prognostication by incorporating clinical and cytokine data, and to investigate how these factors may interact with the effect of mean lung dose (MLD) on RILT. MATERIALS AND METHODS: Data from 125 patients treated from 2004 to 2013 with definitive radiotherapy for stages I-III NSCLC on four prospective clinical trials were analyzed. Plasma levels of 30 cytokines were measured pretreatment, and at 2 and 4weeks midtreatment. Penalized logistic regression models based on combinations of MLD, clinical factors, and cytokine levels were developed. Cross-validated estimates of log-likelihood and area under the receiver operating characteristic curve (AUC) were used to assess accuracy. RESULTS: In prognosticating grade 3 or greater RILT by MLD alone, cross-validated log-likelihood and AUC were -28.2 and 0.637, respectively. Incorporating clinical features and baseline cytokine levels increased log-likelihood to -27.6 and AUC to 0.669. Midtreatment cytokine data did not further increase log-likelihood or AUC. Of the 30 cytokines measured, higher levels of 13 decreased the effect of MLD on RILT, corresponding to a lower odds ratio for RILT per Gy MLD, while higher levels of 4 increased the association. CONCLUSIONS: Although the added prognostic benefit from cytokine data in our model was modest, understanding how clinical and biologic factors interact with the MLD-RILT relationship represents a novel framework for understanding and investigating the multiple factors contributing to radiation-induced toxicity

nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea.

Clearance of the airway is dependent on directional mucus flow across the mucociliary epithelium, and deficient flow is implicated in a range of human disorders. Efficient flow relies on proper polarization of the multiciliated cells and sufficient ciliary beat frequency. We show that NO, produced by nNOS in the multiciliated cells of the mouse trachea, controls both the planar polarity and the ciliary beat frequency and is thereby necessary for the generation of the robust flow. The effect of nNOS on the polarity of ciliated cells relies on its interactions with the apical networks of actin and microtubules and involves RhoA activation. The action of nNOS on the beat frequency is mediated by guanylate cyclase; both NO donors and cGMP can augment fluid flow in the trachea and rescue the deficient flow in nNOS mutants. Our results link insufficient availability of NO in ciliated cells to defects in flow and ciliary activity and may thereby explain the low levels of exhaled NO in ciliopathies