ELUCIDATION OF THE MOLECULAR MECHANISMS OF ACTION OF PINI

The enzyme Pinl is a peptidyl-prolyl isomerase (PPIase) that structurally consists of an N-terminal WW interaction domain and a C-terminal catalytic or PPIase domain. The understanding of how these two domains work together and perform the many functions discovered in cells is incomplete. Therefore, we hypothesize that Pinl acts as an extra regulatory step in signalling pathways by first binding to targets with its WW domain and then catalyzing the isomerization of those same proteins using its PPIase domain. To gain insights into how Pinl performs its molecular function, we mutated specific residues of Pinl and examined both their ability to support viability in yeast and isomerase activity. We determined that in the phospho-specific binding loop of the PPIase domain K63 was the most important basic residue for Pinl function and activity while only one contact from R68 or R69 was needed. Furthermore, by mutating the Pinl catalytic residue, Cl 13, to both D and S, we showed that a negative charge at this position is more important than a nucleophile. Finally, extensive mutagenesis of two conserved active site histidines, H59 and HI57, determined that these two residues are not as important as Cl 13 for Pinl function or activity. Instead, protein stability experiments suggested a structural role for both histidines. Collectively, these results led us to propose a new non-covalent mechanism for Pinl catalysis. We also examined the binding of Pinl mutants to full-length targets and surprisingly found that a binding-deficient mutation in the PPIase domain, R68/69A, had a lower affinity for most Pinl targets. We also discovered two classes of Pinl binding proteins: Class I proteins bind both the WW and PPIase domains of Pinl while Class II proteins mainly bind the WW. We proposed, based upon structures of the WW and PPIase domains bound to peptides, that the differences between Class I and Class II binding may relate to the presence of a proline at the +1 position. These results have provided novel insights into the binding of the two domains of Pin 1 to full-length targets. Taken together, these studies have expanded the knowledge of the molecular mechanisms of Pinl action in cells

Elemental depth profiling of thin film chalcogenides using MeV ion beam analysis

The comprehensive characterisation is one of many technical challenges in the fabrication of photovoltaic devices from novel materials. We show how the application of recent advances in MeV ion beam analysis, providing the selfconsistent treatment of Rutherford backscattering and particle induced X-ray emission spectra, makes a new set of powerful complementary elemental depth profiling techniques available for all thin film technologies, including the chalcopyrite compound semiconductors. We will give and discuss a detailed analysis of a CuInAl metallic precursor film, showing how similar methods are also applicable to other films of interest

The co-development and feasibility-testing of an innovative digital animation intervention (DAISI) to reduce the risk of maternal sepsis in the postnatal period

YesIntroduction: Sepsis is one of the most common causes of mortality in postnatal women globally and many other women who develop sepsis are left with severe morbidity. Women’s knowledge of postnatal sepsis and how it can be prevented by simple changes to behaviour is lacking. Methods: This paper describes the co-development and feasibility testing of a digital animation intervention called DAISI (digital animation in service improvement). This DAISI is designed to enhance postnatal women’s awareness of sepsis and how to reduce their risk of developing the condition. We co-designed the digital animation over a six-month period underpinned by theory, best evidence and key stakeholders, translated it into Urdu then assessed its use, firstly in a focus group with women from different Black, Asian and Minority Ethnic (BAME) groups and secondly with 15 clinical midwives and 15 women (including BAME women). Following exposure to the intervention, midwives completed a questionnaire developed from the COM-B behaviour change model and women participated in individual and focus group interviews using similar questions. Results: The animation was considered acceptable, culturally sensitive and simple to implement and follow. Discussion: DAISI appears to be an innovative solution for use in maternity care to address difficulties with the postnatal hospital discharge process. We could find no evidence of digital animation being used in this context and recommend a study to test it in practice prior to adopting its use more widely. If effective, the DAISI principle could be used in other maternity contexts and other areas of the NHS to communicate health promotion information.This study was funded by Translate Medtech, Leeds City Region. DAISI was developed by HMA Digital, Barnsley, UK

2018-2019 Philharmonia No. 3

Concert Date & Time: November 10, 2018 at 7:30 PM and November 11, 2018 at 4:00 PM 2018 Concerto Competition Winners Program Concerto for Viola and Orchestra / Béla Bartók Kayla Williams, viola Violin Concerto / Alban Berg Melanie Riordan, violin Flute Concerto No. 1 / André Jolivet Lydia Roth, flute Piano Concerto in F / George Gershwin Bailey-Michelle Collins, pianohttps://spiral.lynn.edu/conservatory_philharmonia/1133/thumbnail.jp

Defining adherence to therapeutic exercise for musculoskeletal pain : a systematic review

Objective To establish the meaning of the term ‘adherence’ (including conceptual and measurement definitions) in the context of therapeutic exercise (TE) for musculoskeletal (MSK) pain. Design Systematic review using a search strategy including terms for: adherence, TE and MSK pain. Identified studies were independently screened for inclusion by two researchers. Two independent researchers extracted data on: study type; MSK pain population; type of TE used; definitions, parameters, measurement methods and values of adherence. Data sources Seven electronic databases were searched from inception to December 2016. Eligibility criteria Any study type featuring TE for adults with MSK pain and containing a definition of adherence, or a description of how adherence was measured. Results 459 studies were identified and 86 were included in the review. Most were prospective cohort studies and featured back and/or neck pain. Strengthening and stretching were the most common types of TE. A clearly identifiable definition of adherence was provided in 40% of the studies, with 12% using the same definition. Exercise frequency was the most commonly measured parameter of adherence, with self-report logs the most common measurement method. The most common value range used to determine satisfactory adherence was 80%–99% of the recommended exercise dose. Conclusion No single definition of adherence to TE was apparent. We found no definition of adherence that specifically related to TE for MSK pain or described the dimensions of TE that should be measured. We recommend conceptualising adherence to TE for MSK pain from the perspective of all relevant stakeholders

Single-Cell Lipidomics Using Analytical Flow LC-MS Characterizes the Response to Chemotherapy in Cultured Pancreatic Cancer Cells

In this work, we demonstrate the development and first application of nanocapillary sampling followed by analytical flow liquid chromatography–mass spectrometry for single-cell lipidomics. Around 260 lipids were tentatively identified in a single cell, demonstrating remarkable sensitivity. Human pancreatic ductal adenocarcinoma cells (PANC-1) treated with the chemotherapeutic drug gemcitabine can be distinguished from controls solely on the basis of their single-cell lipid profiles. Notably, the relative abundance of LPC(0:0/16:0) was significantly affected in gemcitabine-treated cells, in agreement with previous work in bulk. This work serves as a proof of concept that live cells can be sampled selectively and then characterized using automated and widely available analytical workflows, providing biologically relevant outputs

Automated synthesis of PET radiotracers by copperâ mediated 18Fâ fluorination of organoborons: Importance of the order of addition and competing protodeborylation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142980/1/jlcr3583_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142980/2/jlcr3583.pd

Housing stability and diabetes among people living in New York city public housing

Public housing provides affordable housing and, potentially, housing stability for low-income families. Housing stability may be associated with lower incidence or prevalence and better management of a range of health conditions through many mechanisms. We aimed to test the hypotheses that public housing residency is associated with both housing stability and reduced risk of diabetes incidence, and the relationship between public housing and diabetes risk varies by levels of housing stability. Using 2004-16 World Trade Center Health Registry data, we compared outcomes (housing stability measured by sequence analysis of addresses, self-reported diabetes diagnoses) between 730 New York City public housing residents without prevalent diabetes at baseline and 730 propensity score-matched non-public housing residents. Sequence analysis found 3 mobility patterns among all 1460 enrollees, including stable housing (65%), limited mobility (27%), and unstable housing patterns (8%). Public housing residency was associated with stable housing over 12 years. Diabetes risk was not associated with public housing residency; however, among those experiencing housing instability, a higher risk of diabetes was found among public housing versus non-public housing residents. Of those stably housed, the association remained insignificant. These findings provide important evidence for a health benefit of public housing via housing stability among people living in public housing

Synoptic-scale controls on the δ18O in precipitation across Beringia

Oxygen isotope records of precipitation (δ18Oprecip) from Beringia are thought to reflect synoptic-scale circulation changes associated with the Aleutian Low. To delineate the spatial pattern of δ18Oprecip associated with the two dominant modes of Aleutian Low circulation, we combine modern δ18Oprecip and deuterium excess data with climate reanalysis and back-trajectory modelling. Aleutian Low strength and position are revealed to systematically affect regional moisture source and δ18Oprecip; whereby a strengthened Aleutian Low causes lower (higher) δ18Oprecip in western (eastern) Beringia. We compare a new 100-year-long δ18O record from the Aleutian Islands with the North Pacific Index, the primary indicator of Aleutian Low strength, and find a significant positive relationship (r = 0.43, p < 0.02, n = 28) that tracks late 20th century change. This study demonstrates synoptic-scale circulation controls on our isotope record, and provides a coherent framework for interpreting existing and emerging paleo-isotope data from the region