38 research outputs found
Equal Lives: Parenthood and Caring in the Workplace
Equal Lives reveals that men and women have very similar attitudes and desires in relation to balancing work and caring responsibilities. During 2018, over 10,000 employees told us about their experiences, attitudes and aspirations in relation to balancing professional employment with personal caring responsibilities for both children and adults. Equal Lives shows that caring responsibilities outside of work impacts how engaged employees are at work, their ability to progress and impetus to leave, as well as relationships within teams at work. It suggests that if employers are to create healthy and productive workplace cultures they will need to recognise individual employee needs and aspirations outside of work; taking steps to reduce the gap between their employeesâ attitudes and the reality of day-to-day organisational behaviours. Currently, in the UK, nine in ten households with dependent children have working parents
Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains
BACKGROUND: Despite multiple causes, Chronic Kidney Disease is commonly associated with proteinuria. A previous study on Non Obese Diabetic mice (NOD), which spontaneously develop type 1 diabetes, described histological and gene expression changes incurred by diabetes in the kidney. Because proteinuria is coincident to diabetes, the effects of proteinuria are difficult to distinguish from those of other factors such as hyperglycemia. Proteinuria can nevertheless be induced in mice by peritoneal injection of Bovine Serum Albumin (BSA). To gain more information on the specific effects of proteinuria, this study addresses renal changes in diabetes resistant NOD-related mouse strains (NON and NOD.B10) that were made to develop proteinuria by BSA overload. METHODS: Proteinuria was induced by protein overload on NON and NOD.B10 mouse strains and histology and microarray technology were used to follow the kidney response. The effects of proteinuria were assessed and subsequently compared to changes that were observed in a prior study on NOD diabetic nephropathy. RESULTS: Overload treatment significantly modified the renal phenotype and out of 5760 clones screened, 21 and 7 kidney transcripts were respectively altered in the NON and NOD.B10. Upregulated transcripts encoded signal transduction genes, as well as markers for inflammation (Calmodulin kinase beta). Down-regulated transcripts included FKBP52 which was also down-regulated in diabetic NOD kidney. Comparison of transcripts altered by proteinuria to those altered by diabetes identified mannosidase 2 alpha 1 as being more specifically induced by proteinuria. CONCLUSION: By simulating a component of diabetes, and looking at the global response on mice resistant to the disease, by virtue of a small genetic difference, we were able to identify key factors in disease progression. This suggests the power of this approach in unraveling multifactorial disease processes
Immunophilin FKBP52 induces Tau-P301L filamentous assembly in vitro and modulates its activity in a model of tauopathy
A ÎČ-Turn Motif in the Steroid Hormone Receptorâs Ligand-Binding Domains Interacts with the Peptidyl-prolyl Isomerase (PPIase) Catalytic Site of the Immunophilin FKBP52
International audienceThe immunophilin FKBP52 interacts with nuclear steroid hormone receptors. Studying the crystal structure of human estrogen receptor alpha (hER alpha) and using nuclear magnetic resonance, we show here that the short V(364)PGF(367) sequence, which is located within its ligand-binding domain and adopts a type II beta-turn conformation in the protein, binds the peptidyl-prolyl isomerase (PPIase or rotamase) FK1 domain of FKBP52. Interestingly, this turn motif displays strong similarities with the FKBP52 FK1 domain-binding moiety of macrolide immunomodulators such as rapamycin and GPI-1046, an immunophilin ligand with neuroprotective characteristics. An increase in the hydrophobicity of the residue preceding the proline and cyclization of the VPGF peptide strengthen its recognition by the FK1 domain of FKBP52. Replacement of the Pro residue with a dimethylproline also enhances this interaction. Our study not only contributes to a better understanding of how the interaction between the FK1 domain of FKBP52 and steroid hormone receptors most likely works but also opens new avenues for the synthesis of FKBP52 FK1 peptide ligands appropriate for the control of hormone-dependent physiological mechanisms or of the functioning of the Tau protein. Indeed, it has been shown that FKBP52 is involved in the intraneuronal dynamics of the Tau protein
A ÎČâTurn Motif in the Steroid Hormone Receptorâs Ligand-Binding Domains Interacts with the Peptidyl-prolyl Isomerase (PPIase) Catalytic Site of the Immunophilin FKBP52
The immunophilin
FKBP52 interacts with nuclear steroid hormone
receptors. Studying the crystal structure of human estrogen receptor
α (hERα) and using nuclear magnetic resonance, we show
here that the short V<sup>364</sup>PGF<sup>367</sup> sequence, which
is located within its ligand-binding domain and adopts a type II ÎČ-turn
conformation in the protein, binds the peptidyl-prolyl isomerase (PPIase
or rotamase) FK1 domain of FKBP52. Interestingly, this turn motif
displays strong similarities with the FKBP52 FK1 domain-binding moiety
of macrolide immunomodulators such as rapamycin and GPI-1046, an immunophilin
ligand with neuroprotective characteristics. An increase in the hydrophobicity
of the residue preceding the proline and cyclization of the VPGF peptide
strengthen its recognition by the FK1 domain of FKBP52. Replacement
of the Pro residue with a dimethylproline also enhances this interaction.
Our study not only contributes to a better understanding of how the
interaction between the FK1 domain of FKBP52 and steroid hormone receptors
most likely works but also opens new avenues for the synthesis of
FKBP52 FK1 peptide ligands appropriate for the control of hormone-dependent
physiological mechanisms or of the functioning of the Tau protein.
Indeed, it has been shown that FKBP52 is involved in the intraneuronal
dynamics of the Tau protein
Microtubule-associated protein 2 (MAP2) is a neurosteroid receptor
The neurosteroid pregnenolone (PREG) and its chemically synthesized analog 3ÎČ-methoxypregnenolone (MePREG) bind to microtubule-associated protein 2 (MAP2) and stimulate the polymerization of microtubules. PREG, MePREG, and progesterone (PROG; the physiological immediate metabolite of PREG) significantly enhance neurite outgrowth of nerve growth factor-pretreated PC12 cells. However, PROG, although it binds to MAP2, does not increase the immunostaining of MAP2, contrary to PREG and MePREG. Nocodazole, a microtubule-disrupting agent, induces a major retraction of neurites in control cultures, but pretreatment with PREG/MePREG is protective. Decreasing MAP2 expression by RNA interference does not modify PROG action, but it prevents the stimulatory effects of PREG and MePREG on neurite extension, showing that MAP2 is their specific receptor