Do the mutations of C1GALT1C1 gene play important roles in the genetic susceptibility to Chinese IgA nephropathy?

Background: The deficiency of beta 1,3 galactose in hinge region of IgA1 molecule played a pivotal role in pathogenesis of IgA nephropathy (IgAN). Cosmc, encoded by C1GALT1C1 gene, was indispensable to beta 1,3 galactosylation of IgA1. We designed a serial study to investigate the relationship between the mutations of C1GALT1C1 gene and the genetic susceptibility to IgAN. Methods: Nine hundred and thirty-eight subjects, including 661 patients with IgAN and 277 healthy controls were enrolled in the study. Firstly, single nucleotide polymorphisms (SNPs) in the promoter region of C1GALT1C1 gene were screened. Then the c.-347-190G> A was analyzed by PCR-restriction fragment length polymorphism (PCR-RFLP) for further case-control association analysis. Secondly the somatic mutations of DNAs from peripheral blood B lymphocytes were detected in 15 patients and 7 normal controls. Results: No significant association was observed between the different alleles or genotypes of c.347-190G>A and IgAN. The patients with different genotypes of C1GALT1C1 gene did not significantly associate with clinical manifestations, including hematuria, proteinuria, and serum creatinine of patients with IgAN. There was no somatic mutation detected in total 202 clones of 22 individuals. Conclusion: The c.-347-190G>A polymorphism and the somatic mutation of encoding region of C1GALT1C1 gene were not significantly related to the genetic susceptibility to IgAN in Northern Chinese population.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000271285100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Genetics & HereditySCI(E)PubMed1ARTICLE1011

Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3–8.9 μM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity–dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.Charles A. Dana Foundation. Brain and Immuno-ImagingRaymond and Beverley Sackler FoundationNational Institutes of Health (U.S.) (grant R01-DA28299)National Institutes of Health (U.S.) (grant DP2-OD2441)National Institutes of Health (U.S.) (grant R01-GM068664)Jacobs Institute for Molecular Engineering for Medicine. Jacobs Institute for Molecular Engineering for MedicineNational Institutes of Health (U.S.) (grant R01-DE013023

Dynamics of direct inter-pack encounters in endangered African wild dogs

Aggressive encounters may have important life history consequences due to the potential for injury and death, disease transmission, dispersal opportunities or exclusion from key areas of the home range. Despite this, little is known of their detailed dynamics, mainly due to the difficulties of directly observing encounters in detail. Here, we describe detailed spatial dynamics of inter-pack encounters in African wild dogs (Lycaon pictus), using data from custom-built high-resolution GPS collars in 11 free-ranging packs. On average, each pack encountered another pack approximately every 7 weeks and met each neighbour twice each year. Surprisingly, intruders were more likely to win encounters (winning 78.6% of encounters by remaining closer to the site in the short term). However, intruders did tend to move farther than residents toward their own range core in the short-term (1 h) post-encounter, and if this were used to indicate losing an encounter, then the majority (73.3%) of encounters were won by residents. Surprisingly, relative pack size had little effect on encounter outcome, and injuries were rare (<15% of encounters). These results highlight the difficulty of remotely scoring encounters involving mobile participants away from static defendable food resources. Although inter-pack range overlap was reduced following an encounter, encounter outcome did not seem to drive this, as both packs shifted their ranges post-encounter. Our results indicate that inter-pack encounters may be lower risk than previously suggested and do not appear to influence long-term movement and ranging

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

Educational paper: Abusive Head Trauma Part I. Clinical aspects

Abusive Head Trauma (AHT) refers to the combination of findings formerly described as shaken baby syndrome. Although these findings can be caused by shaking, it has become clear that in many cases there may have been impact trauma as well. Therefore a less specific term has been adopted by the American Academy of Pediatrics. AHT is a relatively common cause of childhood neurotrauma with an estimated incidence of 14–40 cases per 100,000 children under the age of 1 year. About 15–23% of these children die within hours or days after the incident. Studies among AHT survivors demonstrate that approximately one-third of the children are severely disabled, one-third of them are moderately disabled and one-third have no or only mild symptoms. Other publications suggest that neurological problems can occur after a symptom-free interval and that half of these children have IQs below the 10th percentile. Clinical findings are depending on the definitions used, but AHT should be considered in all children with neurological signs and symptoms especially if no or only mild trauma is described. Subdural haematomas are the most reported finding. The only feature that has been identified discriminating AHT from accidental injury is apnoea. Conclusion: AHT should be approached with a structured approach, as in any other (potentially lethal) disease. The clinician can only establish this diagnosis if he/she has knowledge of the signs and symptoms of AHT, risk factors, the differential diagnosis and which additional investigations to perform, the more so since parents seldom will describe the true state of affairs spontaneously

Well-Being as Harmony

In this paper, I sketch out a novel theory of well-being according to which well-being is constituted by harmony between mind and world. The notion of harmony I develop has three aspects. First there is correspondence between mind and world in the sense that events in the world match the content of our mental states. Second there is positive orientation towards the world, meaning that we have pro-attitudes towards the world we find ourselves in. Third there is fitting response to the world. Taken together these three aspects make up an ideal of being attuned to, or at home in, the world. Such harmony between mind and world constitutes well-being. Its opposite – being disoriented, ill-at-ease in, or hostile to the world – makes a life go poorly. And, as we shall see, many of the things that intuitively contribute to well-being are instantiating one or more of the three aspects of harmony

An exploration of knowledge, attitudes and advice given by health professionals to parents in Ireland about the introduction of solid foods. A pilot study

<p>Abstract</p> <p>Background</p> <p>For the purposes of this paper "weaning is defined as the introduction of the first solid foods to infants". Global recommendations by the World Health Organisation (WHO) recommend that all infants be exclusively breast-fed for the first six months of life. No global recommendations have been made for formula fed infants. In Europe it is recommended that weaning foods should be introduced between 18 weeks and 26 weeks regardless of whether infants are breast or formula fed. In the United Kingdom it is recommended that solids be introduced at around six-months for both breast and formula fed infants. In Ireland official guidelines recommend that breast fed infants should be introduced solids at 6 months of age while for formula fed infants the recommendation is for 4 months. The disparity between these global, European, UK and local recommendations may be a source of confusion for parents and health care professional based in Ireland. Emerging evidence suggests that babies in Ireland are given solid foods before the recommended age but there has been little investigation of the weaning advice provided by health professionals. Since community health professionals have routine parent interactions in the pre-weaning and early-weaning period and hence are in a unique position to positively influence parental weaning decisions, this study aimed to explore their knowledge, attitudes and advice practices about weaning.</p> <p>Methods</p> <p>A mixed-methods approach was used for the research, commencing with a multi-disciplinary focus group to guide and develop a questionnaire. Questionnaires were then distributed in a postal survey to General Practitioners (GPs) (<it>n </it>179), Practice Nurses (PNs) (<it>n </it>121), Public Health Nurses (PHNs) (<it>n </it>107) and Community Dieticians (CDs) (<it>n </it>8).</p> <p>Results</p> <p>The results indicate varying levels of knowledge of official weaning recommendations and a variety of advice practices. CDs and PHNs acknowledged a clear role in providing weaning advice while demonstrating high confidence levels in providing this advice. However, 19% of PNs and 7% of GP respondents did not acknowledge that they have a role in providing weaning advice to parents; even though Health Service Executive (HSE) written literature given to parents states that they should seek information from PNs and GPs.</p> <p>Conclusion</p> <p>Small pockets of misinformation about the introduction of solid foods persist amongst health professionals which may lead to inconsistent advice for parents. Further research is needed.</p