Redshifts of galaxies close to bright QSO lines of sight

To expand the known number of low-redshift galaxies which lie close to bright ($V < 17.2$) QSO lines of sight, we have identified 24 galaxies within 11 arcmins of nine QSOs which have been observed with the Hubble Space Telescope (HST). Galaxies are found between redshifts of $0.0114-0.145$ and lie between $39-749$ $h^{-1}$ kpc from QSO sightlines. Knowing the redshifts of these galaxies has already proved important in understanding results from HST programmes designed to search for UV absorption lines from low-redshift galaxies, and will enable future observations to probe the halos of these galaxies in detail.Comment: MNRAS in press. 9 pages LaTeX using MNRAS sty. Postscript figures are excluded due to large size. Paper with figures can be obtained from http://www.roe.ac.uk/research/bowen1.ps.

Trends in New South Wales infant hospital admission rates in the first year of life: population-based study

Objective: To examine the trends in hospital admissions in the first year of life and identify whether changes in maternal and infant risk factors explain any changes Design: Population-based study using de-identified linked health data. Participants: All 788,798 liveborn infants delivered in New South Wales from 2001 to 2009 with a linked birth and hospital record. Main outcome measures: The number of infants readmitted to hospital at least once, up to one year of age, per 100 livebirths each year; changes in maternal and infant risk factors were assessed using logistic regression. Results: The number of infants admitted to hospital up to age one decreased 10.5%, from 18.4 per 100 births in 2001 to 16.5 in 2009. Fifty five per cent of this decrease could be explained by changes in factors that are associated with likelihood of hospitalisation; length of stay during the birth admission, maternal age and maternal smoking. The rate of admissions for jaundice and feeding difficulties increased significantly over the study period, while admissions for infections decreased. Conclusions: There has been a decrease in the rate of infants admitted to hospital in the first year of life, which can be partly explained by increasing maternal age, decreasing maternal smoking and a shift to shorter length of hospital stay at birth. Improved maternal and neonatal care in hospital and increased postnatal support at home may have contributed to reduced risk of readmission. The introduction of government policies may explain the rest of the decrease

Hospitalisations from one to six years of age: Effects of Gestational Age and Severe Neonatal Morbidity

Background: To investigate whether the adverse infant health outcomes associated with early birth and severe neonatal morbidity (SNM) persist beyond the first year of life and impact on paediatric hospitalisations for children up to six years of age. Methods: The study population included all singleton live births, >32 weeks gestation in New South Wales, Australia in 2001-2005, with follow-up to six years of age. Birth data were probabilistically linked to hospitalisation data (n=392,964). The odds of hospitalisation, mean hospital length of stay (LOS) and costs, and cumulative LOS were evaluated by gestational age and SNM using multivariable analyses. Results: A total of 74,341 (18.9%) and 41,404 (10.5%) infants were hospitalized once and more than once, respectively. SNM was associated with increased odds of hospitalisation once (adjusted odds ratio (aOR) 1.16 [95% CI 1.10, 1.22]), and more than once (aOR 1.51 [1.42, 1.60]). Decreasing gestational age was associated with increasing odds of hospitalisation more than once from aOR 1.19 at 37-38 weeks to 1.49 at 33-34 weeks. Average LOS and costs per hospital admission were increased with SNM but not with decreasing gestational age. Cumulative LOS was significantly increased with SNM and decreasing gestational age. Conclusions: Adverse effects of SNM and early birth persist between one and six years of age. Strategies to prevent early birth and reduce SNM, and to increase health monitoring of vulnerable infants throughout childhood may help reduce paediatric hospitalisations.NHMRC, NSW Health Population Health and Health Services Gran

The microbiota-gut-brain axis:An emerging therapeutic target in chemotherapy-induced cognitive impairment

Chemotherapy-induced cognitive impairment (CICI) is an ill-defined complication of chemotherapy treatment that places a significant psychosocial burden on survivors of cancer and has a considerable impact on the activities of daily living. CICI pathophysiology has not been clearly defined, with candidate mechanisms relating to both the direct cytotoxicity of chemotherapy drugs on the central nervous system (CNS) and more global, indirect mechanisms such as neuroinflammation and blood brain barrier (BBB) damage. A growing body of research demonstrates that changes to the composition of the gastrointestinal microbiota is an initiating factor in numerous neurocognitive conditions, profoundly influencing both CNS immunity and BBB integrity. Importantly, chemotherapy causes significant disruption to the gastrointestinal microbiota. While microbial disruption is a well-established factor in the development of chemotherapy-induced gastrointestinal toxicities (largely diarrhoea), its role in CICI remains unknown, limiting microbial-based therapeutics or risk prediction strategies. Therefore, this review aims to synthesise and critically evaluate the evidence addressing the microbiota-gut-brain axis as a critical factor influencing the development of CICI

Brn-3b enhances the pro-apoptotic effects of p53 but not its induction of cell cycle arrest by cooperating in trans-activation of bax expression

The Brn-3a and Brn-3b transcription factor have opposite and antagonistic effects in neuroblastoma cells since Brn-3a is associated with differentiation whilst Brn-3b enhances proliferation in these cells. In this study, we demonstrate that like Brn-3a, Brn-3b physically interacts with p53. However, whereas Brn-3a repressed p53 mediated Bax expression but cooperated with p53 to increase p21(cip1/waf1), this study demonstrated that co-expression of Brn-3b with p53 increases trans-activation of Bax promoter but not p21(cip1/waf1). Consequently co-expression of Brn-3b with p53 resulted in enhanced apoptosis, which is in contrast to the increased survival and differentiation, when Brn-3a is co-expressed with p53. For Brn-3b to cooperate with p53 on the Bax promoter, it requires binding sites that flank p53 sites on this promoter. Furthermore, neurons from Brn-3b knock-out (KO) mice were resistant to apoptosis and this correlated with reduced Bax expression upon induction of p53 in neurons lacking Brn-3b compared with controls. Thus, the ability of Brn-3b to interact with p53 and modulate Bax expression may demonstrate an important mechanism that helps to determine the fate of cells when p53 is induced

Loss of Bladder Epithelium Induced by Cytolytic Mast Cell Granules

Programmed death and shedding of epithelial cells is a powerful defense mechanism to reduce bacterial burden during infection but this activity cannot be indiscriminate because of the critical barrier function of the epithelium. We report that during cystitis, shedding of infected bladder epithelial cells (BECs) was preceded by the recruitment of mast cells (MCs) directly underneath the superficial epithelium where they docked and extruded their granules. MCs were responding to interleukin-1β (IL-1β) secreted by BECs after inflammasome and caspase-1 signaling. Upon uptake of granule-associated chymase (mouse MC protease 4 [mMCPT4]), BECs underwent caspase-1-associated cytolysis and exfoliation. Thus, infected epithelial cells require a specific cue for cytolysis from recruited sentinel inflammatory cells before shedding

Mechanisms and Role of Dendritic Membrane Trafficking for Long-Term Potentiation

Long-term potentiation (LTP) of excitatory synapses is a major form of plasticity for learning and memory in the central nervous system. While the molecular mechanisms of LTP have been debated for decades, there is consensus that LTP induction activates membrane trafficking pathways within dendrites that are essential for synapse growth and strengthening. Current models suggest that key molecules for synaptic potentiation are sequestered within intracellular organelles, which are mobilized by synaptic activity to fuse with the plasma membrane following LTP induction. While the identity of the factors mobilized to the plasma membrane during LTP remain obscure, the field has narrowly focused on AMPA-type glutamate receptors. Here, we review recent literature and present new experimental data from our lab investigating whether AMPA receptors trafficked from intracellular organelles directly contribute to synaptic strengthening during LTP. We propose a modified model where membrane trafficking delivers distinct factors that are required to maintain synapse growth and AMPA receptor incorporation following LTP. Finally, we pose several fundamental questions that may guide further inquiry into the role of membrane trafficking for synaptic plasticity

The Chemerin-CMKLR1 Axis is Functionally important for Central Regulation of Energy Homeostasis

YesChemerin is an adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism, and has been hypothesized as a link between obesity and type II diabetes. In humans affected by obesity, chemerin gene expression in peripheral tissues and circulating levels are elevated. In mice, plasma levels of chemerin are upregulated by high-fat feeding and gain and loss of function studies show an association of chemerin with body weight, food intake and glucose homeostasis. Therefore, chemerin is an important blood-borne mediator that, amongst its other functions, controls appetite and body weight. Almost all studies of chemerin to date have focused on its release from adipose tissue and its effects on peripheral tissues with the central effects largely overlooked. To demonstrate a central role of chemerin, we manipulated chemerin signaling in the hypothalamus, a brain region associated with appetite regulation, using pharmacological and genetic manipulation approaches. Firstly, the selective chemerin receptor CMKLR1 antagonist α-NETA was administered i.c.v. to rats to test for an acute physiological effect. Secondly, we designed a short-hairpin-RNA (shRNA) lentivirus construct targeting expression of CMKLR1. This shRNA construct, or a control construct was injected bilaterally into the arcuate nucleus of male Sprague Dawley rats on high-fat diet (45%). After surgery, rats were maintained on high-fat diet for 2 weeks and then switched to chow diet for a further 2 weeks. We found a significant weight loss acutely and inhibition of weight gain chronically. This difference became apparent after diet switch in arcuate nucleus-CMKLR1 knockdown rats. This was not accompanied by a difference in blood glucose levels. Interestingly, appetite-regulating neuropeptides remained unaltered, however, we found a significant reduction of the inflammatory marker TNF-α suggesting reduced expression of CMKLR1 protects from high-fat diet induced neuroinflammation. In white and brown adipose tissue, mRNA expression of chemerin, its receptors and markers of adipogenesis, lipogenesis and brown adipocyte activation remained unchanged confirming that the effects are driven by the brain. Our behavioral analyses suggest that knockdown of CMKLR1 had an impact on object recognition. Our data demonstrate that CMKLR1 is functionally important for the central effects of chemerin on body weight regulation and neuroinflammation.This work was funded in part by the Academy of Medical Sciences, the Wellcome Trust, the Government of Business, Energy and Industrial Strategy and the British Heart Foundation and Diabetes United Kingdom [SBF004/1063] (GH), the Society for Endocrinology Equipment Grant (GH, RD), the University of Bradford (GH, KP, SK) and Nottingham Trent University (RD)

Long term follow up of high risk children: who, why and how?

Background: Most babies are born healthy and grow and develop normally through childhood. There are, however, clearly identifiable high-risk groups of survivors, such as those born preterm or with ill-health, who are destined to have higher than expected rates of health or developmental problems, and for whom more structured and specialised follow-up programs are warranted. Discussion This paper presents the results of a two-day workshop held in Melbourne, Australia, to discuss neonatal populations in need of more structured follow-up and why, in addition to how, such a follow-up programme might be structured. Issues discussed included the ages of follow-up, and the personnel and assessment tools that might be required. Challenges for translating results into both clinical practice and research were identified. Further issues covered included information sharing, best practice for families and research gaps. Summary A substantial minority of high-risk children has long-term medical, developmental and psychological adverse outcomes and will consume extensive health and education services as they grow older. Early intervention to prevent adverse outcomes and the effective integration of services once problems are identified may reduce the prevalence and severity of certain outcomes, and will contribute to an efficient and effective use of health resources. The shared long-term goal for families and professionals is to work toward ensuring that high risk children maximise their potential and become productive and valued members of society. Electronic supplementary material The online version of this article (doi:10.1186/1471-2431-14-279) contains supplementary material, which is available to authorized users