Optimization of metal-cyclization of alpha-MSH peptide analogs used in the treatment and detection of melanoma

Abstract only availableOver the past few years Dr. Quinn and his lab have made significant progress in the development of a melanoma treatment drug. Based upon peptide analogs of the alpha-melanocyte stimulating hormone, Α-MSH, Dr. Quinn has developed a metal cyclized drug that shows very promising results in therapy as well as early detection/imaging of melanoma tumors. The cyclization of the peptide around a metal core was shown to greatly increase the affinity of the peptide for its target. There are slight problems with the cyclization process that needed to be resolved or limited in order to make the synthesis of the drug as efficient as possible. The primary problem with the cyclization of the peptide is the fact that two main products are produced. One of these products is caused by the histidine residue swinging down and binding with the metal core. Histidine is one of the four amino acids directly involved with receptor recognition and thus this product's tumor uptake is at least 50% lower. Three variables were explored in hopes of reducing this second unwanted product. A new and simpler process developed by Fridkin et. al. ¹ was first considered. HPLC was used to purify the two major products and their identities were confirmed using mass spectrometry. The new procedure proved to be slightly more effective as the old procedure. With the old procedure roughly 32.3% of the two major products were of the undesired compound, however, using this new procedure this was reduced to 23.4%. A variation of the new procedure was then tried. Instead of dissolving the linear peptide in water, as the procedure called to do, the peptide was dissolved using DMF. This modification showed a significant change in the percentage of the two products. Of the two major products only 12.8% of the total was of the unwanted product thus producing 87.2% of the desired cyclized peptide. Finally an addition of an extra amino acid residue near the beginning of the sequence was tried in hopes of moving the histidine residue far enough away from the metal core in order to limit their interaction. Current tests are still being performed to determine whether or not this will be successful. (1) Fridkin, G., Bonsera, T.A., Litman, P., and Gilon, C. Nucl. Med Biol 32, 39-50, 2005.Molecular Imaging Progra

4th International Conference - Sexuality and Cancer Breast Cancer

Breast cancer patients and the artists involved in the highly innovative ComMA research programme led an experiential workshop attended by 100 health professional delegates. The experiential workshop explained how patients and artists together explored sexual problems encountered following breast cancer treatment. This novel and highly collaborative approach empowered patients to use art and new forms of artistic expression as an alternative language to express and communicate their feelings of emotional and physical trauma using visual metaphors. ComMA enabled patients to explore and express their feelings through the use of collage, drawing on items such as gowns, which had a deep meaning in the context of their treatment, to enable them to express their feelings openly. Work co-produced by the artists and patients was shared at the workshop to challenge health professionals to understand the patients’ concerns, insecurities and difficulties in communicating their sexual and relationship problems

Cheshire Wirral Partnership - Research Conference

The presentation, experiential workshop and exhibition for 100 health practitioners took place at an annual event which shares good practice across the Cheshire Wirral Partnership (CWP) NHS Trust. The highly innovative ComMA research programme was nominated by CWP for a recognition award and shortlisted for the Outstanding Contribution to Research Development and Innovation. The presentation and experiential workshop explained how patients and artists together explored sexual problems encountered following cancer treatment. This novel and highly collaborative approach empowered patients to use art and new forms of artistic expression as an alternative language to express and communicate their feelings of emotional and physical trauma using visual metaphors. ComMA enabled patients to explore and express their feelings through the use of collage and drawing on items such as gowns, which had a deep meaning in the context of their treatment, to enable them to express their feelings and to seek appropriate support. Work co-produced by the artists and patients was shared at the workshop to allow health professionals to understand these issues from a patient’s perspective

The Role of Radioactivities in Astrophysics

I present both a history of radioactivity in astrophysics and an introduction to the major applications of radioactive abundances to astronomy

The Age of the Galactic Disk

I review different methods devised to derive the age of the Galactic Disk, namely the Radio-active Decay (RD), the Cool White Dwarf Luminosity Function (CWDLF), old opne clusters (OOC) and the Color Magnitude Diagram (CMD) of the stars in the solar vicinity. I argue that the disk is likely to be 8-10 Gyr old. Since the bulk of globulars has an age around 13 Gyr, the possibility emerges that the Galaxy experienced a minimum of Star Formation at the end of the halo/bulge formation. This minimum might reflect the time at which the Galaxy started to acquire material to form the disk inside-out.Comment: 10 pages, 4 figure, invited review, in "The chemical evolution of the Milky Way : Stars vs Clusters, Vulcano (Italy), 20-24 September 199

‘I Already Know the City, I Don’t Have to Explore it’: Adjustments to ‘Sense of Place’ for ‘Local’ UK University Students

Recent conceptualisations of place have sought to reconsider place as being the sedentary equivalent to mobility, instead recognising its dynamism and its potential for evoking powerful emotional responses. These notions hold particular resonance in the realm of higher education, with discussions emerging of the important influence place may hold for students as they progress through university.Although this has been recognised from the perspective of ‘mobile’ students, what is less clear is how these notions of placemight influence the trajectories of ‘local’ students, specifically how feelings of place disruption or identity dislocation might spill out into their non-student lives and their wider sense of ‘being’ students (or nonstudents) within what are often highly emotive and memory-laden places. This is important as the process of ‘re-sensing’ place through the lens of a student may challenge long-established conceptions of the city for ‘local’ students

Ectodermal dysplasias: Classification and organization by phenotype, genotype and molecular pathway

An international advisory group met at the National Institutes of Health in Bethesda, Maryland in 2017, to discuss a new classification system for the ectodermal dysplasias (EDs) that would integrate both clinical and molecular information. We propose the following, a working definition of the EDs building on previous classification systems and incorporating current approaches to diagnosis: EDs are genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands. Genetic variations in genes known to be associated with EDs that affect only one derivative of the ectoderm (attenuated phenotype) will be grouped as non‐syndromic traits of the causative gene (e.g., non‐syndromic hypodontia or missing teeth associated with pathogenic variants of EDA “ectodysplasin”). Information for categorization and cataloging includes the phenotypic features, Online Mendelian Inheritance in Man number, mode of inheritance, genetic alteration, major developmental pathways involved (e.g., EDA, WNT “wingless‐type,” TP63 “tumor protein p63”) or the components of complex molecular structures (e.g., connexins, keratins, cadherins)

Adapting relationships with place: Investigating the evolving place attachment and ‘sense of place’ of UK higher education students during a period of intense transition

In recent years interest has emerged regarding the geographies of higher education students, particularly in patterns of mobility and dispersion. While anecdotal rhetoric suggests a ‘typical student’ exists within UK institutions. What resonates is the notion that students are inherently heterogeneous, experiencing University in differing ways and times according to their circumstances and year of study. This paper uses ‘walking interviews’ conducted with University of Portsmouth students as a method to unpack how ‘non-local’ students might go about interpreting their sense of place within their term-time location. This methodology was designed specifically to ensure discussions of ‘sense of place’ remain directly in the context of the city and recognises the adaptive relationships students have with their term-time locations. This is important as there is a tendency within the literature to focus solely on the transition into University, ignoring that students often experience pressures throughout their degree pathway. These pressures can be linked to various social and spatial changes, such as insecurities regarding fitting in amongst unfamiliar peer groups or a lack of confidence concerning engagement with academic and non-academic practices, and draws attention to the non-linearity of students’ associations with their term-time location

A Dedicated Promoter Drives Constitutive Expression of the Cell-Autonomous Immune Resistance GTPase, Irga6 (IIGP1) in Mouse Liver

Background: In general, immune effector molecules are induced by infection. Methodology and Principal Findings: However, strong constitutive expression of the cell-autonomous resistance GTPase, Irga6 (IIGP1), was found in mouse liver, contrasting with previous evidence that expression of this protein is exclusively dependent on induction by IFNc. Constitutive and IFNc-inducible expression of Irga6 in the liver were shown to be dependent on transcription initiated from two independent untranslated 59 exons, which splice alternatively into the long exon encoding the full-length protein sequence. Irga6 is expressed constitutively in freshly isolated hepatocytes and is competent in these cells to accumulate on the parasitophorous vacuole membrane of infecting Toxoplasma gondii tachyzoites. Conclusions and Significance: The role of constitutive hepatocyte expression of Irga6 in resistance to parasites invading from the gut via the hepatic portal system is discussed

Spatial dislocation and affective displacement: youth perspectives on gentrification in London

Analyses of contemporary processes of gentrification have been primarily produced from adult perspectives with little focus on how age affects or mediates urban change. However, in analysing young people’s responses to transformations in their neighbourhood we argue that there is evidence for a more complex relationship between ‘gentrifiers’ and residents than existing arguments of antagonism or tolerance would suggest. Using a participatory video methodology to document experiences of gentrification in the east London borough of Hackney, we found that young people involved in this study experienced their transforming city through processes of spatial dislocation and affective displacement. The former incorporated a sense of disorientation in the temporal disjunctions of the speed of change, while the latter invoked the embodiment of a sense of not belonging generated within classed and intercultural interactions. However, there are expressions of ambivalence rather than straightforward rejection. Benefits of gentrification were noted including conditions of alterity and the possibility to transcend normative behaviours that they found uncomfortable. Young people demonstrated the capacity to re-imagine their relationship with the complex spaces they call home. The findings suggest a need to reframe debates on gentrification to include a more nuanced understanding of its differential impact on young people