Publications by authors named "David Dawson"

Unlabelled: Proteolysis of hydrophobic helices is required for complete breakdown of every transmembrane protein trafficked to the lysosome and sustains high rates of endocytosis. However, the lysosomal mechanisms for degrading hydrophobic domains remain unknown. Combining lysosomal proteomics with functional genomic data mining, we identify Lysosomal Leucine Aminopeptidase (LyLAP; formerly Phospholipase B Domain-Containing 1) as the hydrolase most tightly associated with elevated endocytic activity.

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Article Synopsis
  • Macropinocytosis is a survival strategy used by cancer cells, especially in nutrient-poor environments, relying heavily on glutamine to sustain themselves, particularly in pancreatic ductal adenocarcinoma (PDAC) cells.
  • The atypical protein kinase C (aPKC) enzymes, specifically PKCζ and PKCι, play a crucial role in regulating macropinocytosis by interacting with scaffold proteins that influence cell structure and function.
  • The research shows that aPKCs enhance macropinocytosis through the relocation of Par3 to microtubules, and their depletion adversely affects cell viability, which can be reversed by restoring macropinocytosis, highlighting the significance of aPKCs in supporting
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The pleiotropic roles of nSMase2-generated ceramide include regulation of intracellular ceramide signaling and exosome biogenesis. We investigated the effects of eliminating nSMase2 on early and advanced PDA, including its influence on the microenvironment. Employing the KPC mouse model of pancreatic cancer, we demonstrate that pancreatic epithelial nSMase2 ablation reduces neoplasia and promotes a PDA subtype switch from aggressive basal-like to classical.

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  • Hypereosinophilic syndrome (HES) leads to high levels of eosinophils in the blood and tissues, causing organ damage, with gastrointestinal issues being a common manifestation.
  • A 28-year-old female patient suffered from severe gastrointestinal symptoms and was diagnosed with idiopathic HES and eosinophilic esophagitis, resistant to multiple treatments.
  • After starting dupilumab, a recently FDA-approved treatment, the patient achieved remission, resolving her gastrointestinal issues and allowing her to return to a normal diet without needing total parenteral nutrition.
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  • Researchers aimed to understand the heterogeneity of pancreatic ductal adenocarcinoma by focusing on epigenetically regulated pathways that affect its progression.
  • They discovered that hypermethylation of the Hepatocyte Nuclear Factor 4A (HNF4A) gene leads to its suppression, which is linked to the growth and severity of pancreatic cancer.
  • The study concludes that loss of HNF4A due to DNA methylation contributes to the disease's development and is associated with worse survival outcomes for patients.
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Background: Pancreatic neuroendocrine tumors (pNETs) are genomically diverse tumors. The management of newly diagnosed well-differentiated pNETs is limited by a lack of sensitivity of existing biomarkers for prognostication. Our goal was to investigate the potential utility of genetic markers as a predictor of progression-free survival (PFS) and recurrence-free survival (RFS).

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Purpose: To synthesise qualitative research on individuals diagnosed with (or reportedly showing traits of) borderline pattern personality disorder who underwent dialectical behaviour therapy, aiming to comprehend their perceptions of change processes and the therapy's effects.

Method: A comprehensive literature search was conducted across multiple online databases and grey literature sources. Papers were quality appraised using an adapted version of the Critical Appraisal Skills Programme tool.

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Recent publications within Contextual Behavioral Science provided a rationale for the expansion of intervention efficacy research using methods that capture idiographic factors and processes. We conducted a systematic review of the use and quality of single-case experimental designs (SCED) within the Acceptance and Commitment Therapy (ACT) literature in adult clinical populations. The systematic review was conducted according to PRISMA guidelines and the databases CINAHL, MEDLINE, PsycINFO, PsycArticles and OpenGrey were searched for peer-reviewed articles.

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Anguillid eel populations are under threat globally. A particularly vulnerable life-cycle stage is the migration of mature adult eels downstream from freshwater habitats through estuaries into the sea to spawn. This study investigated the factors associated with downstream migration of the short-finned eel Anguilla australis (Richardson 1841) from a coastal wetland (Lake Condah) in south-east Australia, using acoustic telemetry.

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Article Synopsis
  • Macropinocytosis is a survival mechanism for cancer cells, especially in nutrient-poor environments like tumors, allowing them to scavenge nutrients such as glutamine.
  • In pancreatic ductal adenocarcinoma (PDAC), the atypical protein kinase C (aPKC) enzymes, specifically PKCζ and PKCι, play a crucial role in regulating this nutrient uptake process.
  • The study reveals that these aPKCs interact with cell polarity proteins and are influenced by EGFR signaling and the CREM transcription factor to facilitate macropinocytosis, which is essential for the growth and survival of PDAC cells in vivo.
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Objectives: Individuals with a diagnosis of FND report experiencing stigma in medical settings, however, there is a paucity of research exploring their experiences in psychological services. The aim of this research was to explore experiences of accessing UK psychological services, from the perspective of those with FND.

Methods: This study utilised a qualitative approach with data collected from semi-structured interviews (n = 15) and analysed using reflexive thematic analysis.

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Objectives: Fibroblast activation protein alpha (FAP) is highly expressed by cancer-associated fibroblasts in multiple epithelial cancers. The aim of this study was to characterize FAP expression in sarcomas to explore its potential utility as a diagnostic and therapeutic target and prognostic biomarker in sarcomas.

Methods: Available tissue samples from patients with bone or soft tissue tumors were identified at the University of California, Los Angeles.

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Purpose: Haematopoietic stem cell transplantation (HSCT) is an intensive procedure associated with elevated psychological distress, particularly during the initial stages. Based on self-regulatory theory, a prophylactic group intervention was developed to mitigate this distress by targeting perceptions of HSCT and coping. This study evaluated the feasibility of delivering the intervention and of conducting a randomised clinical trial to assess efficacy.

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A 43-year-old man with a growing mass in the right groin, concerned for liposarcoma, underwent MRI and 68 Ga-fibroblast activation protein inhibitor (FAPI)-46 PET/CT before surgery. Fibroblast activation protein inhibitor PET/CT demonstrated increased uptake (SUV max , 3.2) predominantly in the solid portion, where MRI showed gadolinium enhancement.

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Background: Pancreatic adenocarcinoma (PDAC) persists as a malignancy with high morbidity and mortality that can benefit from new means to characterize and detect these tumors, such as radiogenomics. In order to address this gap in the literature, constructed a transcriptomic-CT radiogenomic (RG) map for PDAC.

Methods: In this Institutional Review Board approved study, a cohort of subjects (n = 50) with gene expression profile data paired with histopathologically confirmed resectable or borderline resectable PDAC were identified.

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Introduction: The Social Communication Questionnaire is used to identify children and young people (CYP) who may require formal ASD assessment. However, there is a paucity of research on its utility in Children and Adolescent Mental Health Services. This evaluation aimed to determine the sensitivity and specificity of the Social Communication Questionnaire (SCQ) in a UK, Midlands CAMHS service.

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There are many definitions of recovery in mental health. Community Rehabilitation Teams (CRTs) aim to support the mental health recovery of people. The Individual Recovery Outcomes Counter (I.

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Objectives: Extracellular vesicles (EVs) are lipid bound vesicles secreted by cells into the extracellular environment. Studies have implicated EVs in cell proliferation, epithelial-mesenchymal transition, metastasis, angiogenesis, and mediating the interaction of tumor cells and microenvironment. A systematic characterization of EVs from pancreatic cancer cells and cancer-associated fibroblasts (CAFs) would be valuable for studying the roles of EV proteins in pancreatic tumorigenesis.

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Objectives: The present demand for child and adolescent mental health services exceeds the capacity for service provision. Greater research is required to understand the utility of accessible self-help interventions, such as mobile apps. This study sought to investigate whether use of a mental health app, underpinned by CBT, led to changes in psychological distress amongst adolescents.

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Background: Multiple sclerosis (MS) is a chronic condition of the central nervous system, affecting around 1 in every 600 people in the UK, with 130 new diagnoses every week. Cognitive difficulties are common amongst people with MS, with up to 70% experiencing deficits in higher-level brain functions-such as planning and problem-solving, attention, and memory. Cognitive deficits make it difficult for people with MS to complete everyday tasks and limit their abilities to work, socialise, and live independently.

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Pancreatic ductal adenocarcinoma (PDAC) is correlated with poor outcomes because of limited therapeutic options. Laminin-5 gamma-2 (LAMC2) plays a critical role in key biological processes. However, the detailed molecular mechanism and potential roles of LAMC2 in PDAC stay unexplored.

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Background: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the central nervous system (CNS), increasing in incidence and prevalence across both developed and developing countries. Cognitive difficulties are common in MS sufferers with 70% experiencing difficulties in higher-level brain functioning such as planning, attention, problem solving, and memory. Computerised cognitive training programmes may hold promise as a treatment option for improving cognitive function in people with MS, subject to exploring and addressing potential barriers to usability and acceptability.

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