Publications by authors named "LEAHY D"

Article Synopsis
  • Researchers have successfully transported key membrane proteins, including EGFR and the Insulin Receptor, into extracellular vesicles (EVs) for in-depth structural and functional analysis, showcasing the potential of EVs for studying membrane protein interactions.
  • Using techniques like cryo-electron tomography, they observed that these proteins, particularly EGFR, form clusters and maintain a specific distance from the membrane, which challenges previous assumptions about protein arrangement.
  • This work advances our understanding of EGFR's role in signaling and development, highlighting its implications in cancer therapies and providing a new approach for examining human membrane proteins in conditions similar to their natural environment.
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  • * The review analyzed 204 papers, selecting 18 that demonstrated a wide range in self-harm rates—between 1.5% and 23% among adolescents (ages 15-18), with higher incidents reported in females and often occurring at home.
  • * Findings highlighted that while many youths sought help from friends or family before or after self-harm episodes, professional help was rarely pursued, underscoring the need for better psychoeducation for families and enhanced mental health services.
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A vaccine is needed to combat the Chlamydia epidemic. Replication-deficient viral vectors are safe and induce antigen-specific T-cell memory. We tested the ability of intramuscular immunization with modified vaccinia Ankara (MVA) virus or chimpanzee adenovirus (ChAd) expressing chlamydial outer membrane protein (OmcB) or the secreted protein, chlamydial protease-like activating factor (CPAF), to enhance T-cell immunity and protection in mice previously infected with plasmid-deficient Chlamydia muridarum CM972 and elicit protection in naïve mice.

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Chlamydia is an obligate intracellular bacterial pathogen responsible for disease and infertility across multiple species. Currently vaccines are being studied to help reduce the prevalence of this disease. The main advantage of protein subunit vaccines is their high degree of safety although this is traded off with the requirement for multiple booster doses to achieve complete protection.

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Background: Online question banks are the most widely used education resource amongst medical students. Despite this there is an absence of literature outlining how and why they are used by students. Drawing on Deci and Ryan's self-determination theory, our study aimed to explore why and how early-stage medical students use question banks in their learning and revision strategies.

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() infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for , undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as () in pigs.

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Objectives: People with significant mental health difficulties (SMHD) experience inequities in cancer care. This study aims to deepen understanding of cancer care for individuals with SMHD.

Method: We conducted semi-structured interviews with seven individuals with SMHD regarding their experiences accessing and engaging with cancer care from August 2021 to February 2022.

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Purpose: This study aimed to evaluate whether a high-throughput high-resolution PGT-A method can detect copy number variants (CNVs) that could have clinical implications for patients and their embryos.

Methods: A prospective analysis of PGT-A cases was conducted using a high-resolution SNP microarray platform with over 820,000 probes. Cases where multiple embryos possessed the same segmental imbalance were identified, and preliminary PGT-A reports were issued recommending either parental microarray or conventional karyotyping to identify CNVs or translocations.

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Background: Systems thinking approaches are increasingly being used by communities to address complex chronic disease. This paper reports on the VicHealth Local Government Partnership (VLGP) which sought to co-create improvements in the health and well-being of children and young people by working with local government in Victoria, Australia.

Methods: The VLGP included a series of health promotion modules, aimed at creating policy, programme and practice changes across local government.

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Article Synopsis
  • The text discusses a method for catalyzing asymmetric hydrogenation of indazole-containing enamides, specifically for synthesizing zavegepant, a new migraine treatment.
  • It highlights the effectiveness of both neutral bis(phosphine)cobalt(II) and cationic bis(phosphine)cobalt(I) complexes as precatalysts, achieving high yields and selectivity in the hydrogenation reactions.
  • Additionally, it mentions the successful hydrogenation of a specific enamide on a large scale (20 grams), showing practical application in the synthesis process.
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Small proteins perform a diverse array of functions, from microbial competition, to endocrine signaling, to building biomaterials. Microbial systems that can produce recombinant small proteins enable discovery of new effectors, exploration of sequence activity relationships, and have the potential for delivery. However, we lack simple systems for controlling small-protein secretion from Gram-negative bacteria.

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Recombinant human neutrophil elastase (rHNE), a serine protease, was expressed in Pichia pastoris. Glycosylation sites were removed via bioengineering to prevent hyper-glycosylation (a common problem with this system) and the cDNA was codon optimized for translation in Pichia pastoris. The zymogen form of rHNE was secreted as a fusion protein with an N-terminal six histidine tag followed by the heme binding domain of Cytochrome B5 (CytB5) linked to the N-terminus of the rHNE sequence via an enteropeptidase cleavage site.

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Unlabelled: Microcins are peptide antibiotics secreted by Gram-negative bacteria that inhibit the growth of neighboring microbes. They are exported from the cytosol to the environment in a one-step process through a specific type I secretion system (T1SS). While the rules governing export of natural or non-native substrates have been resolved for T1SSs that secrete large proteins, relatively little is known about substrate requirements for peptides exported through T1SSs that secrete microcins.

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The Epidermal Growth Factor Receptor (EGFR) is a Receptor Tyrosine Kinase that mediates cell proliferation and differentiation events during development and maintenance of complex organisms. Formation of specific, ligand-dependent EGFR dimers is a key step in stimulating EGFR signaling, and crystal structures of active, dimeric forms of isolated EGFR extracellular regions and kinase domains have revealed much about how dimer interactions regulate EGFR activity. The nature and role of the transmembrane region in regulating EGFR activity remains less clear, however.

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Unlabelled: Referrals to Child and Adolescent Mental Health Services (CAMHS) have increased in recent years. Services are already under-resourced and the adverse psychological impact of Covid-19 is likely to increase demand. Accordingly, an understanding of prevalence of mental health (MH) disorders among youth is imperative to help inform and plan services.

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Background: Many adults do not reach the recommended exercise participation guidelines, often citing lack of time as a barrier. Reduced exertion high-intensity training (REHIT) is a mode of exercise that takes as few as 10 min and has been shown to be as effective as other modalities. The Fitness Fatness Index (FFI) is a recently developed index that is used to predict cardiovascular disease (CVD) risk.

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All young people are entitled to knowledge and support that protects their sexual and reproductive health. School-based education is the most opportune setting for young people to have equitable access to sexual and reproductive health education. However, there is room for significant improvements in the provision of sexual and reproductive health education globally, and a range of barriers to be addressed.

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Preconception health affects fertility, pregnancy, and future health outcomes but public awareness of this is low. Our aims were to rank priorities for preconception care (PCC), develop strategies to address these priorities, and establish values to guide future work in preconception healthcare in Australia. A Delphi technique involved two rounds of online voting and mid-round workshops.

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Objectives: Inequities in cancer care contribute to higher rates of cancer mortality for individuals with significant mental health difficulties (SMHD) compared to the general population. The aim of the current systematic review was to identify, appraise and synthesise qualitative evidence of patient and clinician/system barriers and facilitators to cancer screening and treatment for individuals with SMHD.

Methods: We conducted a systematic search across three electronic databases in May 2020 and we carried out a second search across five electronic databases in January 2021.

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Under the shielding effect of nanomicelles, a sustainable micellar technology for the design and convenient synthesis of ligand-free oxidizable ultrasmall Pd(0) nanoparticles (NPs) and their subsequent catalytic exploration for couplings of water-sensitive acid chlorides in water is reported. A proline-derived amphiphile, PS-750-M, plays a crucial role in stabilizing these NPs, preventing their aggregation and oxidation state changes. These NPs were characterized using C nuclear magnetic resonance (NMR), infrared (IR), and surface-enhanced Raman scattering (SERS) spectroscopy to evaluate the carbonyl interactions of PS-750-M with Pd.

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Human neutrophil elastase (HNE) is a uniquely destructive serine protease with the ability to unleash a wave of proteolytic activity by destroying the inhibitors of other proteases. Although this phenomenon forms an important part of the innate immune response to invading pathogens, it is responsible for the collateral host tissue damage observed in chronic conditions such as chronic obstructive pulmonary disease (COPD), and in more acute disorders such as the lung injuries associated with COVID-19 infection. Previously, a combinatorially selected activity-based probe revealed an unexpected substrate preference for oxidised methionine, which suggests a link to oxidative pathogen clearance by neutrophils.

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Highly valued products resulting from reductive aminations utilizing shelf-stable bisulfite addition compounds of aldehydes can be made under aqueous micellar catalysis conditions. Readily available α-picolineborane serves as the stoichiometric hydride source. Recycling of the aqueous reaction medium is easily accomplished, and several applications to targets in the pharmaceutical industry are documented.

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The amphiphile PS-750-M generates stable, phosphine ligand-free, and catalytically active ultrasmall Pd(II) nanoparticles (NPs) from Pd(OAc), preventing their precipitation, polymerization, and oxidation state changes. PS-750-M directly interacts with Pd(II) NP surfaces, as confirmed by high-resolution mass spectrometry and IR spectroscopy, resulting in their high stability. The Pd cations in NPs are most likely held together by hydroxides and acetate ions.

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