FeP Nanocatalyst with Preferential [010] Orientation Boosts the Hydrogen Evolution Reaction in Polymer-Electrolyte Membrane Electrolyzer

The development of nonprecious metal electrocatalysts for polymer-electrolyte membrane (PEM) water electrolysis is a milestone for the technology, which currently relies on rare and expensive platinum-group metals. Half-cell measurements have shown iron phosphide materials to be promising alternative hydrogen evolution electrocatalysts, but their realistic performance in flow-through devices remains unexplored. To fill this gap, we report herein the activity and durability of FeP nanocatalyst under application-relevant conditions. Our facile synthesis route proceeds via impregnation of an iron complex on conductive carbon support followed by phosphorization, giving rise to highly crystalline nanoparticles with predominantly exposed [010] facets, which accounts for the high electrocatalytic activity. The performance of FeP gas diffusion electrodes toward hydrogen evolution was examined under application-relevant conditions in a single cell PEM water electrolysis at 22 °C. The FeP cathode exhibited a current density of 0.2 A cm–2 at 2.06 V, corresponding to a difference of merely 0.07 W cm–2 in power input as compared to state-of-the-art Pt cathode, while outperforming other nonprecious cathodes operated at similar temperature. Quantitative product analysis of our PEM device excluded the presence of side reactions and provided strong experimental evidence that our cell operates with 84–100% Faradaic efficiencies and with 4.1 kWh Nm–3 energy consumption. The FeP cathodes exhibited stable performance of over 100 h at constant operation, while their suitability with the intermittency of renewable sources was demonstrated upon 36 h operation at variable power inputs. Overall, the performance as well as our preliminary cost analysis reveal the high potential of FeP for practical applications.</p

Greek mothers' perceptions of their cooperation with the obstetrician and the midwife in the delivery room

Α Ι Μ : The objective of this study was to access the perceptions of mothers of newborns regarding their cooperationwith the midwife and the obstetrician in the delivery room.M A T E R I A L - M E T H O D : The sample consisted of 607 mothers living in Northern Greece. The KuopioInstrument for Mothers (KIM) was used for the data collection.R E S U L T S : All the participants gave birth in a hospital; 403 (66.4%) had vaginal delivery, while 204 (33.6%)gave birth by caesarean section. Women with a vaginal delivery had a better cooperation with the midwife and theobstetrician, in comparison to women who gave birth via caesarean section. The participant mothers had a morepositive experience from their cooperation with the obstetrician than with the midwife.C O N C L U S I O N S : The mothers’ preference for obstetrician’s care than for midwife’s care is probably due tothe commercialisation of gynaecology/obstetrics in Greece, the dramatic increase in the number of obstetriciansover the past decade, and the fact that deliveries carried out solely by midwives have almost disappeared in thecountry. Health policy makers should reinforce the current provision of maternity services and support midwivesto take a more central role during pregnancy, labour, and the postnatal period

Function of the Active Site Lysine Autoacetylation in Tip60 Catalysis

The 60-kDa HIV-Tat interactive protein (Tip60) is a key member of the MYST family of histone acetyltransferases (HATs) that plays critical roles in multiple cellular processes. We report here that Tip60 undergoes autoacetylation at several lysine residues, including a key lysine residue (i.e. Lys-327) in the active site of the MYST domain. The mutation of K327 to arginine led to loss of both the autoacetylation activity and the cognate HAT activity. Interestingly, deacetylated Tip60 still kept a substantial degree of HAT activity. We also investigated the effect of cysteine 369 and glutamate 403 in Tip60 autoacetylation in order to understand the molecular pathway of the autoacetylation at K327. Together, we conclude that the acetylation of K327 which is located in the active site of Tip60 regulates but is not obligatory for the catalytic activity of Tip60. Since acetylation at this key residue appears to be evolutionarily conserved amongst all MYST proteins, our findings provide an interesting insight into the regulatory mechanism of MYST activities

GPR50 Interacts with TIP60 to Modulate Glucocorticoid Receptor Signalling

GPR50 is an orphan G-protein coupled receptor most closely related to the melatonin receptors. The physiological function of GPR50 remains unclear, although our previous studies implicate the receptor in energy homeostasis. Here, we reveal a role for GPR50 as a signalling partner and modulator of the transcriptional co-activator TIP60. This interaction was identified in a yeast-two-hybrid screen, and confirmed by co-immunoprecipitation and co-localisation of TIP60 and GPR50 in HEK293 cells. Co-expression with TIP60 increased perinuclear localisation of full length GPR50, and resulted in nuclear translocation of the cytoplasmic tail of the receptor, suggesting a functional interaction of the two proteins. We further demonstrate that GPR50 can enhance TIP60-coactiavtion of glucocorticoid receptor (GR) signalling. In line with in vitro results, repression of pituitary Pomc expression, and induction of gluconeogenic genes in liver in response to the GR agonist, dexamethasone was attenuated in Gpr50−/− mice. These results identify a novel role for GPR50 in glucocorticoid receptor signalling through interaction with TIP60

Rational design and validation of a Tip60 histone acetyltransferase inhibitor

Histone acetylation is required for many aspects of gene regulation, genome maintenance and metabolism and dysfunctional acetylation is implicated in numerous diseases, including cancer. Acetylation is regulated by histone acetyltransferases (HATs) and histone deacetylases and currently, few general HAT inhibitors have been described. We identified the HAT Tip60 as an excellent candidate for targeted drug development, as Tip60 is a key mediator of the DNA damage response and transcriptional co-activator. Our modeling of Tip60 indicated that the active binding pocket possesses opposite charges at each end, with the positive charges attributed to two specific side chains. We used structure based drug design to develop a novel Tip60 inhibitor, TH1834, to fit this specific pocket. We demonstrate that TH1834 significantly inhibits Tip60 activity in vitro and treating cells with TH1834 results in apoptosis and increased unrepaired DNA damage (following ionizing radiation treatment) in breast cancer but not control cell lines. Furthermore, TH1834 did not affect the activity of related HAT MOF, as indicated by H4K16Ac, demonstrating specificity. The modeling and validation of the small molecule inhibitor TH1834 represents a first step towards developing additional specific, targeted inhibitors of Tip60 that may lead to further improvements in the treatment of breast cancer

dTip60 HAT Activity Controls Synaptic Bouton Expansion at the Drosophila Neuromuscular Junction

Background: Histone acetylation of chromatin plays a key role in promoting the dynamic transcriptional responses in neurons that influence the neuroplasticity linked to cognitive ability, yet the specific histone acetyltransferases (HATs) that create such epigenetic marks remain to be elucidated. Methods and Findings: Here we use the Drosophila neuromuscular junction (NMJ) as a well-characterized synapse model to identify HATs that control synaptic remodeling and structure. We show that the HAT dTip60 is concentrated both pre and post-synaptically within the NMJ. Presynaptic targeted reduction of dTip60 HAT activity causes a significant increase in synaptic bouton number that specifically affects type Is boutons. The excess boutons show a suppression of the active zone synaptic function marker bruchpilot, suggesting defects in neurotransmission function. Analysis of microtubule organization within these excess boutons using immunohistochemical staining to the microtubule associated protein futsch reveals a significant increase in the rearrangement of microtubule loop architecture that is required for bouton division. Moreover, a-tubulin acetylation levels of microtubules specifically extending into the terminal synaptic boutons are reduced in response to dTip60 HAT reduction. Conclusions: Our results are the first to demonstrate a causative role for the HAT dTip60 in the control of synaptic plasticity that is achieved, at least in part, via regulation of the synaptic microtubule cytoskeleton. These findings have implication

Histone methyltransferase Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres

Cells respond to DNA double-strand breaks (DSBs) and uncapped telomeres by recruiting checkpoint and repair factors to the site of lesions. Single-stranded DNA (ssDNA) is an important intermediate in the repair of DSBs and is produced also at uncapped telomeres. Here, we provide evidence that binding of the checkpoint protein Rad9, through its Tudor domain, to methylated histone H3-K79 inhibits resection at DSBs and uncapped telomeres. Loss of DOT1 or mutations in RAD9 influence a Rad50-dependent nuclease, leading to more rapid accumulation of ssDNA, and faster activation of the critical checkpoint kinase, Mec1. Moreover, deletion of RAD9 or DOT1 partially bypasses the requirement for CDK1 in DSB resection. Interestingly, Dot1 contributes to checkpoint activation in response to low levels of telomere uncapping but is not essential with high levels of uncapping. We suggest that both Rad9 and histone H3 methylation allow transmission of the damage signal to checkpoint kinases, and keep resection of damaged DNA under control influencing, both positively and negatively, checkpoint cascades and contributing to a tightly controlled response to DNA damage