Neuromedin U partially mediates leptin-induced hypothalamo-pituitary adrenal (HPA) stimulation and has a physiological role in the regulation of the HPA axis in the rat.

Intracerebroventricular (ICV) administration of the hypothalamic neuropeptide neuromedin U (NMU) or the adipostat hormone leptin increases plasma ACTH and corticosterone. The relationship between leptin and NMU in the regulation of the hypothalamo-pituitary adrenal (HPA) axis is currently unknown. In this study, leptin (1 nM) significantly increased the release of CRH from ex vivo hypothalamic explants by 207 ± 8.4% (P < 0.05 vs. basal), an effect blocked by the administration of anti-NMU IgG. The ICV administration of leptin (10 μg, 0.625 nmol) increased plasma ACTH and corticosterone 20 min after injection [plasma ACTH (picograms per milliliter): vehicle, 63 ± 20, leptin, 135 ± 36, P < 0.05; plasma corticosterone (nanograms per milliliter): vehicle, 285 ± 39, leptin, 452 ± 44, P < 0.01]. These effects were partially attenuated by the prior administration of anti-NMU IgG. Peripheral leptin also stimulated ACTH release, an effect attenuated by prior ICV administration of anti-NMU IgG. We examined the diurnal pattern of hypothalamic NMU mRNA expression and peptide content, plasma leptin, and plasma corticosterone. The diurnal changes in hypothalamic NMU mRNA expression were positively correlated with hypothalamic NMU peptide content, plasma corticosterone, and plasma leptin. The ICV administration of anti-NMU IgG significantly attenuated the dark phase rise in corticosterone [corticosterone (nanograms per milliliter): vehicle, 493 ± 38; NMU IgG, 342 ± 47 (P < 0.05)]. These studies suggest that NMU may play a role in the regulation of the HPA axis and partially mediate leptin-induced HPA stimulation. Copyright © 2006 by The Endocrine Society

The El Nino event of 2015-2016: climate anomalies and their impact on groundwater resources in East and Southern Africa

The impact of climate variability on groundwater storage has received limited attention despite widespread dependence on groundwater as a resource for drinking water, agriculture and industry. Here, we assess the climate anomalies that occurred over Southern Africa (SA) and East Africa, south of the Equator (EASE), during the major El Niño event of 2015–2016, and their associated impacts on groundwater storage, across scales, through analysis of in situ groundwater piezometry and Gravity Recovery and Climate Experiment (GRACE) satellite data. At the continental scale, the El Niño of 2015–2016 was associated with a pronounced dipole of opposing rainfall anomalies over EASE and Southern Africa, north–south of ∼12∘ S, a characteristic pattern of the El Niño–Southern Oscillation (ENSO). Over Southern Africa the most intense drought event in the historical record occurred, based on an analysis of the cross-scale areal intensity of surface water balance anomalies (as represented by the standardised precipitation evapotranspiration index – SPEI), with an estimated return period of at least 200 years and a best estimate of 260 years. Climate risks are changing, and we estimate that anthropogenic warming only (ignoring changes to other climate variables, e.g. precipitation) has approximately doubled the risk of such an extreme SPEI drought event. These surface water balance deficits suppressed groundwater recharge, leading to a substantial groundwater storage decline indicated by both GRACE satellite and piezometric data in the Limpopo basin. Conversely, over EASE during the 2015–2016 El Niño event, anomalously wet conditions were observed with an estimated return period of ∼10 years, likely moderated by the absence of a strongly positive Indian Ocean zonal mode phase. The strong but not extreme rainy season increased groundwater storage, as shown by satellite GRACE data and rising groundwater levels observed at a site in central Tanzania. We note substantial uncertainties in separating groundwater from total water storage in GRACE data and show that consistency between GRACE and piezometric estimates of groundwater storage is apparent when spatial averaging scales are comparable. These results have implications for sustainable and climate-resilient groundwater resource management, including the potential for adaptive strategies, such as managed aquifer recharge during episodic recharge events

DSYB catalyses the key step of dimethylsulfoniopropionate biosynthesis in many phytoplankton

Dimethylsulfoniopropionate (DMSP) is a globally important organosulfur molecule and the major precursor for dimethyl sulfide. These compounds are important info-chemicals, key nutrients for marine microorganisms, and are involved in global sulfur cycling, atmospheric chemistry and cloud formation1,2,3. DMSP production was thought to be confined to eukaryotes, but heterotrophic bacteria can also produce DMSP through the pathway used by most phytoplankton4, and the DsyB enzyme catalysing the key step of this pathway in bacteria was recently identified5. However, eukaryotic phytoplankton probably produce most of Earth’s DMSP, yet no DMSP biosynthesis genes have been identified in any such organisms. Here we identify functional dsyB homologues, termed DSYB, in many phytoplankton and corals. DSYB is a methylthiohydroxybutryate methyltransferase enzyme localized in the chloroplasts and mitochondria of the haptophyte Prymnesium parvum, and stable isotope tracking experiments support these organelles as sites of DMSP synthesis. DSYB transcription levels increased with DMSP concentrations in different phytoplankton and were indicative of intracellular DMSP. Identification of the eukaryotic DSYB sequences, along with bacterial dsyB, provides the first molecular tools to predict the relative contributions of eukaryotes and prokaryotes to global DMSP production. Furthermore, evolutionary analysis suggests that eukaryotic DSYB originated in bacteria and was passed to eukaryotes early in their evolution

Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial

$\textbf{Background:}$ Dairy products are a major contributor to dietary SFA. Partial replacement of milk SFA with unsaturated fatty acids (FAs) is possible through oleic-acid rich supplementation of the dairy cow diet. To assess adherence to the intervention of SFA-reduced, MUFA-enriched dairy product consumption in the RESET (REplacement of SaturatEd fat in dairy on Total cholesterol) study using 4-d weighed dietary records, in addition to plasma phospholipid FA (PL-FA) status. $\textbf{Methods:}$ In a randomised, controlled, crossover design, free-living UK participants identified as moderate risk for CVD (n = 54) were required to replace habitually consumed dairy foods (milk, cheese and butter), with study products with a FA profile typical of retail products (control) or SFA-reduced, MUFA-enriched profile (modified), for two 12-week periods, separated by an 8-week washout period. A flexible food-exchange model was used to implement each isoenergetic high-fat, high-dairy diet (38% of total energy intake (%TE) total fat): control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA). $\textbf{Results:}$ Following the modified diet, there was a smaller increase in SFA (17.2%TE vs. 19.1%TE; p < 0.001) and greater increase in MUFA intake (15.4%TE vs. 11.8%TE; p < 0.0001) when compared with the control. PL-FA analysis revealed lower total SFAs (p = 0.006), higher total cis-MUFAs and trans-MUFAs (both p < 0.0001) following the modified diet. $\textbf{Conclusion:}$ The food-exchange model was successfully used to achieve RESET dietary targets by partial replacement of SFAs with MUFAs in dairy products, a finding reflected in the PL-FA profile and indicative of objective dietary compliance. $\textbf{Trial registration:}$ ClinicalTrials.gov Identifier: NCT02089035 , date 05-01-2014.This work was supported by funding from the Medical Research Council (United Kingdom; Ref: MR/K020218/1)

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Observed controls on resilience of groundwater to climate variability in sub-Saharan Africa

Groundwater in sub-Saharan Africa supports livelihoods and poverty alleviation, maintains vital ecosystems, and strongly influences terrestrial water and energy budgets. Yet the hydrological processes that govern groundwater recharge and sustainability—and their sensitivity to climatic variability—are poorly constrained. Given the absence of firm observational constraints, it remains to be seen whether model-based projections of decreased water resources in dry parts of the region are justified. Here we show, through analysis of multidecadal groundwater hydrographs across sub-Saharan Africa, that levels of aridity dictate the predominant recharge processes, whereas local hydrogeology influences the type and sensitivity of precipitation–recharge relationships. Recharge in some humid locations varies by as little as five per cent (by coefficient of variation) across a wide range of annual precipitation values. Other regions, by contrast, show roughly linear precipitation–recharge relationships, with precipitation thresholds (of roughly ten millimetres or less per day) governing the initiation of recharge. These thresholds tend to rise as aridity increases, and recharge in drylands is more episodic and increasingly dominated by focused recharge through losses from ephemeral overland flows. Extreme annual recharge is commonly associated with intense rainfall and flooding events, themselves often driven by large-scale climate controls. Intense precipitation, even during years of lower overall precipitation, produces some of the largest years of recharge in some dry subtropical locations. Our results therefore challenge the ‘high certainty’ consensus regarding decreasing water resources in such regions of sub-Saharan Africa. The potential resilience of groundwater to climate variability in many areas that is revealed by these precipitation–recharge relationships is essential for informing reliable predictions of climate-change impacts and adaptation strategies

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

PADB : Published Association Database

<p>Abstract</p> <p>Background</p> <p>Although molecular pathway information and the International HapMap Project data can help biomedical researchers to investigate the aetiology of complex diseases more effectively, such information is missing or insufficient in current genetic association databases. In addition, only a few of the environmental risk factors are included as gene-environment interactions, and the risk measures of associations are not indexed in any association databases.</p> <p>Description</p> <p>We have developed a published association database (PADB; <url>http://www.medclue.com/padb</url>) that includes both the genetic associations and the environmental risk factors available in PubMed database. Each genetic risk factor is linked to a molecular pathway database and the HapMap database through human gene symbols identified in the abstracts. And the risk measures such as odds ratios or hazard ratios are extracted automatically from the abstracts when available. Thus, users can review the association data sorted by the risk measures, and genetic associations can be grouped by human genes or molecular pathways. The search results can also be saved to tab-delimited text files for further sorting or analysis. Currently, PADB indexes more than 1,500,000 PubMed abstracts that include 3442 human genes, 461 molecular pathways and about 190,000 risk measures ranging from 0.00001 to 4878.9.</p> <p>Conclusion</p> <p>PADB is a unique online database of published associations that will serve as a novel and powerful resource for reviewing and interpreting huge association data of complex human diseases.</p