An investigation into the unusual linkage isomerization and nitrite reduction activity of a novel tris(2-pyridyl) copper complex

The copper-containing nitrite reductases (CuNIRs) are a class of enzymes that mediate the reduction of nitrite to nitric oxide in biological systems. Metal–ligand complexes that reproduce the salient features of the active site of CuNIRs are therefore of fundamental interest, both for elucidating the possible mode of action of the enzymes and for developing biomimetic catalysts for nitrite reduction. Herein, we describe the synthesis and characterization of a new tris(2-pyridyl) copper complex ([Cu1(NO2)2]) that binds two molecules of nitrite, and displays all three of the common binding modes for NO2−, with one nitrite bound in an asymmetric quasi-bidentate κ2-ONO manner and the other bound in a monodentate fashion with a linkage isomerism between the κ1-ONO and κ1-NO2 binding modes. We use density functional theory to help rationalize the presence of all three of these linkage isomers in one compound, before assessing the redox activity of [Cu1(NO2)2]. These latter studies show that the complex is not a competent nitrite reduction electrocatalyst in non-aqueous solvent, even in the presence of additional proton donors, a finding which may have implications for the design of biomimetic catalysts for nitrite reduction

Does national policy in England help deliver better and more consistent care for those at the end of life?

Objectives: To explore the extent to which national policy in end of life care in England influences and guides local practice, to ensure that care for patients over the age 75 years is of a consistently good quality. Method: This paper reports on phase one of a larger study and focuses its discussion on the high level (macro) determinants emerging from the analysis. Fifteen in-depth interviews were conducted with professionals involved in the development of English policy in end of life care. Results: Factors influencing the quality of end of life care were stratified into three system levels: meso, macro and micro. English national policy was reported to be an important macro-level determinant of effective outcomes and examples were provided to demonstrate how policy was influencing practice. Yet the complexity of the area and the range of interacting contributory factors mean the value of policy alone is hard to assess. At the macro-level concern was voiced around: whether policy was effective in tackling rising inequity; lack of mandatory leverage to exert change relating to end of life outcomes; the impact of ongoing infrastructural change on statutory services; workforce pressures; over-reliance on acute services; and continued abdication of responsibility for end of life care to medical professionals supported by the continued dominance of the medical model of care. Conclusions: The links between the existence of policy at the macro-level of the system, and the effective enactment of good practice remain unclear although strategies are suggested to help achieve greater national consistency in end of life care outcomes. Policymakers must pay attention to the following: controlling the rise in localism and its contribution to regional inequalities; the impact of continuous infrastructural change together with increasing workforce pressures; encouraging broader professional and public responsibility for recognition; and care of those at the end of life

Rapid estimation of relative amide proton exchange rates of 15N-labelled proteins by a straightforward water selective NOESY-HSQC experiment

AbstractA straightforward heteronuclear pseudo-3D NOESY-HSQC pulse sequence using radiation damping to selectively invert magnetization at the water frequency was developed to estimate the amide proton exchange rates in 15N-labelled proteins. The peak intensities in the resultant 2D spectrum allow a direct classification of amide proton exchange rates according to short (ms), intermediate (ms to s) or long (≥ s) residence times. This method was successfully used for the analysis of amide proton exchange rates in the 15N-labelled FruR DNA-binding domain and pertinent information about its dynamics was obtained

A greater decline in female facial attractiveness during middle age reflects women’s loss of reproductive value

Facial attractiveness represents an important component of an individual’s overall attractiveness as a potential mating partner. Perceptions of facial attractiveness are expected to vary with age-related changes in health, reproductive value, and power. In this study, we investigated perceptions of facial attractiveness, power, and personality in two groups of women of pre- and post-menopausal ages (35–50 years and 51–65 years, respectively) and two corresponding groups of men. We tested three hypotheses: (1) that perceived facial attractiveness would be lower for older than for younger men and women; (2) that the age-related reduction in facial attractiveness would be greater for women than for men; and (3) that for men, there would be a larger increase in perceived power at older ages. Eighty facial stimuli were rated by 60 (30 male, 30 female) middle-aged women and men using online surveys. Our three main hypotheses were supported by the data. Consistent with sex differences in mating strategies, the greater age-related decline in female facial attractiveness was driven by male respondents, while the greater age-related increase in male perceived power was driven by female respondents. In addition, we found evidence that some personality ratings were correlated with perceived attractiveness and power ratings. The results of this study are consistent with evolutionary theory and with previous research showing that faces can provide important information about characteristics that men and women value in a potential mating partner such as their health, reproductive value, and power or possession of resources

Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland

Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2−/− mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes

A flexible organic reflectance oximeter array.

Transmission-mode pulse oximetry, the optical method for determining oxygen saturation in blood, is limited to only tissues that can be transilluminated, such as the earlobes and the fingers. The existing sensor configuration provides only single-point measurements, lacking 2D oxygenation mapping capability. Here, we demonstrate a flexible and printed sensor array composed of organic light-emitting diodes and organic photodiodes, which senses reflected light from tissue to determine the oxygen saturation. We use the reflectance oximeter array beyond the conventional sensing locations. The sensor is implemented to measure oxygen saturation on the forehead with 1.1% mean error and to create 2D oxygenation maps of adult forearms under pressure-cuff-induced ischemia. In addition, we present mathematical models to determine oxygenation in the presence and absence of a pulsatile arterial blood signal. The mechanical flexibility, 2D oxygenation mapping capability, and the ability to place the sensor in various locations make the reflectance oximeter array promising for medical sensing applications such as monitoring of real-time chronic medical conditions as well as postsurgery recovery management of tissues, organs, and wounds

Lymphoid Hyperplasia and Lymphoma in Transgenic Mice Expressing the Small Non-Coding RNA, EBER1 of Epstein-Barr Virus

Non-coding RNAs have critical functions in diverse biological processes, particularly in gene regulation. Viruses, like their host cells, employ such functional RNAs and the human cancer associated Epstein-Barr virus (EBV) is no exception. Nearly all EBV associated tumours express the EBV small, non-coding RNAs (EBERs) 1 and 2, however their role in viral pathogenesis remains largely obscure.To investigate the action of EBER1 in vivo, we produced ten transgenic mouse lines expressing EBER1 in the lymphoid compartment using the mouse immunoglobulin heavy chain intronic enhancer Emicro. Mice of several of these EmicroEBER1 lines developed lymphoid hyperplasia which in some cases proceeded to B cell malignancy. The hallmark of the transgenic phenotype is enlargement of the spleen and mesenteric lymph nodes and in some cases enlargement of the thymus, liver and peripheral lymph nodes. The tumours were found to be of B cell origin and showed clonal IgH rearrangements. In order to explore if EBER1 would cooperate with c-Myc (deregulated in Burkitt's lymphoma) to accelerate lymphomagenesis, a cross-breeding study was undertaken with EmicroEBER1 and EmicroMyc mice. While no significant reduction in latency to lymphoma onset was observed in bi-transgenic mice, c-Myc induction was detected in some EmuEBER1 single transgenic tumours, indicative of a functional cooperation.This study is the first to describe the in vivo expression of a polymerase III, non-coding viral gene and demonstrate its oncogenic potential. The data suggest that EBER1 plays an oncogenic role in EBV associated malignant disease

Investigando las fortalezas personales para crear vidas y ambientes positivos: una perspectiva internacional

In today’s world, we face a barrage of difficulties in multiple life spheres. While previous times were not without their challenges, these were often restricted to our own personal, geographically localized worlds. Today, news and social media expose us to never-ending reports of traumatic events and interpersonal violence, making us question human nature and our resiliency. Increasing technological advancements have brought forth new challenges, not only in our relationships with technology, but in how we live our daily lives. Financial uncertainty at both the individual and global level raises doubts about our abilities to afford basic necessities. Climate change is wreaking havoc on the environments we call home. Changing interpersonal dynamics present new challenges to personal, social, and group relationships, often resulting in conflict or isolation. Adolescents and young adults are thrust into this confusing world, often lacking the proper resources to understand and cope with these challenges. Adults facing life’s demands also experience extreme stress, with adverse consequences both at the present as well as later life in the form of physical and mental health issues. Furthermore, we have a tendency to direct attention to our individual weaknesses, exacerbating our experience of difficulties. It is, therefore, no wonder that psychology as a discipline, which seeks to understand the human experience, tends to focus on the deficiencies in our lives. However, as stated by Sheldon and King (2001), it is important for psychologists to deviate from this ‘negative bias’, and instead concentrate on positive human qualities and the promotion of what Maslow (1943, 1987) termed growth needs. This focus is the crux of positive psychology.In today’s world, we face a barrage of difficulties in multiple life spheres. While previous times were not without their challenges, these were often restricted to our own personal, geographically localized worlds. Today, news and social media expose us to never-ending reports of traumatic events and interpersonal violence, making us question human nature and our resiliency. Increasing technological advancements have brought forth new challenges, not only in our relationships with technology, but in how we live our daily lives. Financial uncertainty at both the individual and global level raises doubts about our abilities to afford basic necessities. Climate change is wreaking havoc on the environments we call home. Changing interpersonal dynamics present new challenges to personal, social, and group relationships, often resulting in conflict or isolation. Adolescents and young adults are thrust into this confusing world, often lacking the proper resources to understand and cope with these challenges. Adults facing life’s demands also experience extreme stress, with adverse consequences both at the present as well as later life in the form of physical and mental health issues. Furthermore, we have a tendency to direct attention to our individual weaknesses, exacerbating our experience of difficulties. It is, therefore, no wonder that psychology as a discipline, which seeks to understand the human experience, tends to focus on the deficiencies in our lives. However, as stated by Sheldon and King (2001), it is important for psychologists to deviate from this ‘negative bias’, and instead concentrate on positive human qualities and the promotion of what Maslow (1943, 1987) termed growth needs. This focus is the crux of positive psychology

Child educational progress in Born in Bradford pregnancies affected by gestational diabetes and also exposed to maternal common mental disorders

Abstract Gestational diabetes and the maternal mental disorders of anxiety and depression have been implicated in adverse offspring neuro-behavioural outcomes but these exposures have only been studied in isolation. 1051 children whose mothers were diagnosed with gestational diabetes in UK’s Born in Bradford cohort had linkage to maternal primary care records, providing diagnostic and treatment codes for depression and anxiety. Education record linkage provided results of the Early Years Foundation Stage Profile from the first year of school, aged five. Risk of not attaining a ‘Good level of development’ was analysed using multivariable Poisson regression within a generalised estimating equation framework. Multiple imputation was implemented for missing data. There was limited evidence of increased risk of failure to attain a ‘good level of development’ in those additionally exposed to maternal mental disorders (adjusted RR 1.21; 95% CI 0.94, 1.55). However, there was more evidence in children of Pakistani maternal ethnicity (adjusted RR 1.36; 95% CI 1.04, 1.77) than White British; this may have been driven by English not being the primary language spoken in the home. Therefore there may be groups with GDM in whom it is particularly important to optimise both maternal physical and mental health to improve child outcomes