Publications by authors named "Callum N Watson"

Alzheimer's disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies including AD not only for their use as biomarkers but also for their implications in the therapeutic field. In this study, miRNA and protein profiles were obtained from brain tissues of different stage (Braak III-IV and Braak V-VI) of AD patients and compared to matched controls.

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Article Synopsis
  • The study aimed to explore how salivary small non-coding RNAs (sncRNAs) can help diagnose sports-related concussions in professional rugby players.
  • Saliva samples were collected from over 1,000 players during head injury assessments, identifying 32 sncRNAs that were significantly different between concussed and non-concussed players, with a set of 14 sncRNAs showing strong diagnostic accuracy.
  • The research confirmed that specific salivary sncRNAs can serve as reliable biomarkers for concussion diagnosis, emphasizing the potential for non-invasive testing in sports.
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Inhibitors of the tyrosine kinase Btk have been proposed as novel antiplatelet agents. In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCγ2 in human platelets. Activation is also blocked in patients with X-linked agammaglobulinemia (XLA) caused by a deficiency or absence of Btk.

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Article Synopsis
  • Sport-related concussion management is challenging for clinicians, coaches, and players due to the lack of objective diagnostic tools, leading to undiagnosed concussions and risks of premature return to play.* -
  • The objective of the study is to find parameters like neuroimaging and psychological tests that can help clinicians diagnose concussions, assess injury severity, and guide safe return-to-play decisions.* -
  • The study is an observational cohort study that will assess players before and after sustaining concussions through a series of tests, with results to be shared in conferences and journals.*
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Neurodegenerative diseases (NDs) are becoming increasingly prevalent in the world, with an aging population. In the last few decades, due to the devastating nature of these diseases, the research of biomarkers has become crucial to enable adequate treatments and to monitor the progress of disease. Currently, gene mutations, CSF and blood protein markers together with the neuroimaging techniques are the most used diagnostic approaches.

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Article Synopsis
  • The diagnosis of sports-related concussions is complex due to the lack of objective biomarkers, relying instead on subjective symptoms from athletes, which can lead to health risks if missed.
  • The study aims to identify non-invasive MicroRNA biomarkers in urine and saliva to improve the rapid diagnosis and management of concussions in rugby players.
  • Conducted during the 2017-2019 Rugby Union seasons, the research involves collecting samples from players undergoing head injury assessments and comparing them with control athletes to evaluate the biomarkers' effectiveness.
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Ibrutinib and acalabrutinib are irreversible inhibitors of Bruton tyrosine kinase used in the treatment of B-cell malignancies. They bind irreversibly to cysteine 481 of Bruton tyrosine kinase, blocking autophosphorylation on tyrosine 223 and phosphorylation of downstream substrates including phospholipase C-γ2. In the present study, we demonstrate that concentrations of ibrutinib and acalabrutinib that block Bruton tyrosine kinase activity, as shown by loss of phosphorylation at tyrosine 223 and phospholipase C-γ2, delay but do not block aggregation in response to a maximally-effective concentration of collagen-related peptide or collagen.

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Fibrin has recently been shown to activate platelets through the immunoglobulin receptor glycoprotein VI (GPVI). In the present study, we show that spreading of human platelets on fibrin is abolished in patients deficient in GPVI, confirming that fibrin activates human platelets through the immunoglobulin receptor. Using a series of proteolytic fragments, we show that D-dimer, but not the E fragment of fibrin, binds to GPVI and that immobilized D-dimer induces platelet spreading through activation of Src and Syk tyrosine kinases.

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Gram-negative Escherichia coli cause diseases such as sepsis and hemolytic uremic syndrome in which thrombotic disorders can be found. Direct platelet-bacterium interactions might contribute to some of these conditions; however, mechanisms of human platelet activation by E. coli leading to thrombus formation are poorly understood.

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