The aim of this pilot randomised control trial (RCT) was to test, 1) feasibility and acceptability of a surf therapy program to improve symptoms of mental ill-health among children and adolescents, and 2) the design and procedures of an evaluative study. This pilot RCT compared a 6-week mentor-supported surf therapy program with a wait list control group, in Australian children and adolescents aged 8-18yrs (M age = 11.28, SD = 2.
View Article and Find Full Text PDFBackground: LGBQ+ people (Lesbian, Gay, Bisexual, Queer) are at-risk of discrimination and developing mental health issues within general populations. Limited research has assessed their mental health in emergency services occupations, a population which are known to experience poorer mental health. The current study explores the extent to which sexual orientation is associated with higher rates of mental health issues among emergency personnel.
View Article and Find Full Text PDFLate-life depression is common and often inadequately managed using existing therapies. Depression is also associated with increased markers of inflammation, suggesting a potential role for anti-inflammatory agents. ASPREE-D is a sub-study of ASPREE, a large multi-centre, population-based, double-blind, placebo-controlled trial of aspirin vs placebo in older Australian and American adults (median follow-up: 4.
View Article and Find Full Text PDFImportance: Depression is associated with increased inflammation, which may precede its onset, especially in older people. Some preclinical data suggest potential antidepressant effects of aspirin, supported by limited observational data suggesting lower rates of depression in individuals treated with aspirin. There currently appears to be no evidence-based pharmacotherapies for the primary prevention of depression.
View Article and Find Full Text PDFBackground: Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15-25 years).
Methods: YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial.
Myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) is a common and disabling condition with a paucity of effective and evidence-based therapies, reflecting a major unmet need. Cognitive behavioural therapy and graded exercise are of modest benefit for only some ME/CFS patients, and many sufferers report aggravation of symptoms of fatigue with exercise. The presence of a multiplicity of pathophysiological abnormalities in at least the subgroup of people with ME/CFS diagnosed with the current international consensus "Fukuda" criteria, points to numerous potential therapeutic targets.
View Article and Find Full Text PDFThe heterodimeric nuclear cap-binding complex (CBC) specifically recognizes the monomethylguanosine 5' cap structure of the eukaryotic RNA polymerase II transcripts such as mRNA and U snRNA. The binding is essential for nuclear maturation of mRNA, for nuclear export of U snRNA in metazoans, and for nonsense-mediated decay of mRNA and the pioneer round of translation. We analysed the recognition of the cap by native human CBC and mutants in which each tyrosine that stacks with the 7-methylguanosine moiety was replaced by phenylalanine or alanine and both tyrosines were replaced by phenylalanines.
View Article and Find Full Text PDFMHC-encoded molecules govern adaptive immune responses by presenting peptides to T cell receptors (TCRs). Based on TCR-MHC crystal structures, we revisit the extent of TCR binding degeneracy, a property with important biological consequences because the diversity of TCR ligands that can be encountered exceeds the number of T cell clones present in a person at any one time. We also discuss whether the approximate diagonal binding of TCR on MHC molecules is due to an intrinsic property of the TCR variable regions, or results from the action of the CD4 and CD8 coreceptors during intrathymic T cell selection.
View Article and Find Full Text PDFBinding degeneracy is thought to constitute a fundamental property of the T-cell antigen receptor (TCR), yet its structural basis is poorly understood. We determined the crystal structure of a complex involving the BM3.3 TCR and a peptide (pBM8) bound to the H-2K(bm8) major histocompatibility complex (MHC) molecule, and compared it with the structures of the BM3.
View Article and Find Full Text PDFWe have characterized three different programs of activation for alloreactive CD8 T cells expressing the BM3.3 TCR, their elicitation depending on the characteristics of the stimulating peptide/MHC complex. The high-affinity interaction between the TCR and the K(b)-associated endogenous peptide pBM1 (INFDFNTI) induced a complete differentiation program into effector cells correlated with sustained ERK activation.
View Article and Find Full Text PDFPoly(A)-specific ribonuclease (PARN) is a cap-interacting and poly(A)-specific 3'-exoribonuclease. Here we have investigated how the cap binding complex (CBC) affects human PARN activity. We showed that CBC, via its 80-kDa subunit (CBP80), inhibited PARN, suggesting that CBC can regulate mRNA deadenylation.
View Article and Find Full Text PDFNucleosides Nucleotides Nucleic Acids
December 2005
When the nucleoprotein (N) of nonsegmented negative-strand RNA viruses is expressed in insect cells, it binds to cellular RNA and forms N-RNA complexes just like viral nucleocapsids. However, in virus-infected cells, N is prevented from binding to cellular RNA because a soluble complex is formed between N and the viral phosphoprotein (P), the N degrees -P complex. N is only released from this complex for binding to newly made viral or complementary RNA.
View Article and Find Full Text PDFActa Crystallogr D Biol Crystallogr
December 2002
The nuclear cap-binding complex (CBC) binds the 7-methyl-G(5')ppp(5')N cap structure at the 5' end of pre-messenger and uracil-rich small nuclear RNAs in the nucleus. It mediates interaction of these capped RNAs with various nuclear machineries involved in RNA maturation and is co-exported with them to the cytoplasm. The structure of human CBC, which comprises the subunits CBP20 and CBP80, has previously been determined in a mildly trypsinated form which can no longer bind the cap.
View Article and Find Full Text PDFThe heterodimeric nuclear cap-binding complex (CBC) binds to the 5' cap structure of RNAs in the nucleus and plays a central role in their diverse maturation steps. We describe the crystal structure at 2.1 A resolution of human CBC bound to an m(7)GpppG cap analogue.
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