Cyclin T1-Dependent Genes in Activated CD4+ T and Macrophage Cell Lines Appear Enriched in HIV-1 Co-Factors

HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages, the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that appear to be Cyclin T1-dependent for their induction in activated CD4+ T Jurkat T cells and during differentiation and activation of MM6 cells, a human monocytic cell line. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value<0.00021). The results of siRNA depletion and dominant-negative protein experiments with two CTDGs identified here, CDK11 and Casein kinase 1 gamma 1, suggest that these genes are involved either directly or indirectly in HIV-1 replication. It is likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors

Synthesis and structure of a molecular barium aminebis(phenolate) and its application as an initiator for ring-opening polymerization of cyclic esters

The synthesis and structural characterization of an unusual trinuclear barium aminebis(phenolate) complex are reported along with its application as an initiator for the ring-opening polymerization of epsilon-caprolactone and L-lactide

Prevalence of Mental, Behavioural, and Neurobehavioural Disorders

Individuals with intellectual and developmental disabilities (IDD) are known to be at high risk of developing a comorbid mental or behavioural disorder. However, there has only recently been an increased focus on the epidemiology of such disorders in the older population of people with IDD. Attempting to precisely quantify the prevalence and incidence of disorders in this cohort remain difficult, due to complications associated with diverse sampling methodologies, differing definitions of ‘older’, and variations in diagnostic criteria. Nonetheless, the expanding research base since the 1980s indicates that mental and behavioural disorders occur at higher rates among older people with IDD when compared to their mainstream peers. The prevalence of mental disorders for the older cohort tends to decrease in relation to the severity of the intellectual disability, but the reverse is true for behavioural disorders. Estimated prevalence rates for mental disorders vary considerably, but many studies report rates in the 20–30% range, which is higher than for the general community. Behavioural disorders are also very common in older people with IDD but are again hard to quantify precisely. Observed differences in prevalence between people with IDD and the general community may diminish over the age of 70 as dementias become more commonplace in both populations. Finally, some research indicates a greater likelihood of mental disorder amongst the older female population of people with IDD

Innate immunity in cystic fibrosis lung disease.

Chronic lung disease determines the morbidity and mortality of cystic fibrosis (CF) patients. The pulmonary immune response in CF is characterized by an early and non-resolving activation of the innate immune system, which is dysregulated at several levels. Here we provide a comprehensive overview of innate immunity in CF lung disease, involving (i) epithelial dysfunction, (ii) pathogen sensing, (iii) leukocyte recruitment, (iv) phagocyte impairment, (v) mechanisms linking innate and adaptive immunity and (iv) the potential clinical relevance. Dissecting the complex network of innate immune regulation and associated pro-inflammatory cascades in CF lung disease may pave the way for novel immune-targeted therapies in CF and other chronic infective lung diseases