Five new CYLD mutations in skin appendage tumors and evidence that aspartic acid 681 in CYLD is essential for deubiquitinase activity.

Brooke-Spiegler syndrome, familial cylindromatosis, and familial trichoepithelioma are autosomal-dominant genetic predispositions for benign tumors of skin appendages caused by mutations in the CYLD gene localized on chromosome 16q12-q13. The encoded protein functions as ubiquitin-specific protease (UBP), which negatively regulates NF-kappaB and c-Jun N-terminal kinase (JNK) signaling. We investigated five families affected with these skin neoplasms and identified four premature stop codons and the novel missense mutation D681G in a family in which 11 of 12 investigated tumors were trichoepitheliomas. CYLD protein harboring this missense mutation had a significant reduced ability to inhibit TNF receptor-associated factor (TRAF)2- and TRAF6-mediated NF-kappaB activation, tumor necrosis factor-alpha (TNFalpha)-induced JNK signaling, and to deubiquitinate TRAF2. CYLD-D681G was coimmunoprecipitated by TRAF2, but was unable to cleave K63-linked polyubiquitin chains. Aspartic acid 681 is highly conserved in CYLD homologues and other members of the UBP family, but does not belong to the Cys and His boxes providing the CYLD catalytic triad (Cys601, His871, and Asp889). As reported previously, the homologous residue D295 of HAUSP/USP-7 forms a hydrogen bond with the C-terminal end of ubiquitin and is important for the enzymatic activity. These results underline that D681 in CYLD is required for cleavage of K63-linked polyubiquitin chains.

Implementation of the Action Plan for Health Research 2009-13 - First year report 2009-2010

In November 2009 the Government published an Action Plan for Health Research. The Plan was prepared by the Health Research Group following a commitment set out in Building Ireland’s Smart Economy (December 2008). The Action Plan, which was approved by the Cabinet Committee on Science, Technology and Innovation, provides the lead on national priorities and resource allocation in health research. The Action Plan was prepared to prioritise a programme of actions essential to creating a health research system which supports outstanding individuals, working in world class facilities and conducting leading edge research focused on the needs of patients and the public. The HRG is committed to measuring the success of the Action Plan by the extent to which it meets these deliverables by 2013. One year on, this report reviews the progress being made to implement the Plan.  

Larvicidal activity of the essential oil from Lippia sidoides cham. against Aedes aegypti linn

The aim of this work was to study the larvicidal activity of Lippia sidoides essential oil against Aedes aegypti larvae. The essential oil and its hydrolate (saturated solution of essential oil in water) were obtained by vapor extraction and their chemical composition determined by GL-chromatography coupled to mass spectroscopy. Bioassays were run with the essential oil, pure and diluted hydrolate and with their main constituents thymol and carvacrol. The results obtained showed that L. sidoides essential oil and its hydrolate have larvicidal action against the mosquito A. aegypti, causing an almost instantaneous mortality. Thymol, an alkylated phenol derivative and one of the major components of L. sidoides essential oil, was identified as the active principle responsible for the larvicidal action, causing 100% larval mortality at the lowest tested concentration of 0.017% (w/v). These results suggest that the essential oil of L. sidoides is promising as larvicide against A. aegypti and could be useful in the search of newer, more selective, and biodegradable larvicidal natural compounds to be used in official combat programs and at home.

School food: the essential guide

School food: the essential guide contains a series of eight practical guidance booklets designed to help schools improve pupils' nutrition and implement healthier eating and drinking practices. The booklets provide advice and support for the key areas in which food, drinks and nutrition issues affects schools. Mini case studies support the advice given and, where appropriate, the booklets provide details of recommended further resources. Individual booklets in the series are available as PDF files below: The essential guide Establishing a school food policy Healthier breakfast clubs Healthier breaks Healthier vending Water provision Improving the dining experience in schools Healthier lunch boxes Useful contacts School food: the essential guide is also available in Irish, on request.

Cutting edge: an essential role for Notch-1 in the development of both thymus-independent and -dependent T cells in the gut.

Whereas most T cells arise in the thymus, a distinct lineage of extrathymically derived T cells is present in the gut mucosa. The developmental origin of extrathymic T cells is poorly understood. We show here that Notch-1, a transmembrane receptor involved in T cell fate specification of bipotential T/B precursors in the thymus, is absolutely required for the development of extrathymic (as well as thymus-derived) mature T cells in the intestinal epithelium. In the absence of Notch-1, CD117(+) T cell precursors are relatively more abundant in the gut than the thymus, whereas immature B cells accumulate in the thymus but not the gut. Collectively, these data demonstrate that Notch-1 is essential for both thymic and extrathymic T cell fate specification and further suggest that bipotential T/B precursors that do not receive a Notch-1 signal adopt a B cell fate in the thymus but become developmentally arrested in the gut.

Larvicidal Activity of essential oils from Brazilian plants against Aedes aegypti L.

Aedes aegypti L. is the major vector of dengue fever, an endemic disease in Brazil. In an effort to find effective and affordable ways to control this mosquito, the larvicidal activities of essential oils from nine plants widely found in the Northeast of Brazil were analyzed by measurement of their LC50. The essential oils were extracted by steam distillation and their chemical composition determined by GL-chromatography coupled to mass spectroscopy. The essential oils from Cymbopogon citratus and Lippia sidoides, reported in the literature to have larvicidal properties against A. aegypti, were used for activity comparison. The results show that Ocimum americanum and Ocimum gratissimum have LC50 of 67 ppm and 60 ppm respectively, compared to 63 ppm for L. sidoides and 69 ppm for C. citratus. These results suggest a potential utilization of the essential oil of these two Ocimum species for the control of A. aegypti.

An evaluation of the inappropriate prescribing in older residents in long term care facilities in the greater Cork and Northern Ireland regions using the STOPP and Beers' criteria.

This work has highlighted a number of areas of prescribing concern, for example, the long term use of both benzodiazepines and hypnotics, in older residents residing in long term care facilities. Each of these individual areas should be further investigated to determine the underlying reason(s) for the prescribing concerns in these areas and strategic methods of addressing and preventing further issues should be developed on a national level.This resource was contributed by The National Documentation Centre on Drug Use.

Essential community medicine

This textbook is a definitive guide to the complete spectrum of community medicine. The basic concepts are set out in a clear readable and concise way. The main types of health data are described, as are the principles of disease prevention and its main strategies.This resource was contributed by The National Documentation Centre on Drug Use.

Regional Guideline on the Use of Observation and Therapeutic Engagement in Adult Psychiatric Inpatient Facilities in Northern Ireland

Regional Guideline on the Use of Observation and Therapeutic Engagement in Adult Psychiatric Inpatient Facilities in Northern Ireland

H2O the essential mix

This poster informs about the danger of dehydration caused by taking Ecstasy stating: 'Ecstasy makes you dehydrate and dancing makes you sweat, so if you're doing both sip about a pint of water an hour, have the odd sugary drink and take breaks from dancing'. It also provides contact details for the National Drugs Helpline. Tel: 0800 776600.

Northern Ireland Prevalence Survey of Healthcare-Associated Infections and Antimicrobial Use in Long Term Care Facilities

The Northern Ireland Prevalence Survey of Healthcare-Associated Infections and Antimicrobial Use in Long Term Care Facilities, also known as the 'HALT' survey was conducted as part of the 2013 European Centre for Disease Prevention and Control (ECDC) European HALT survey.In May 2013, 42 Northern Ireland long-term care facilities (nursing and residential homes) participated in a European point prevalence survey of healthcare-associated infections and antimicrobial use. Thirty-one privately owned nursing homes and 11 HSC Trust-controlled residential homes took part.The report and results have highlighted priority areas for future interventions to prevent and control HCAI, antimicrobial stewardship and future local and national prevalence surveys in long-term care facilities. The 2013 European report was published on 5th May 2014.

School food: the essential guide (and Irish translation)

School food: the essential guide contains a series of eight practical guidance booklets designed to help schools improve pupils' nutrition and implement healthier eating and drinking practices. The booklets provide advice and support for the key areas in which food, drinks and nutrition issues affects schools. Mini case studies support the advice given and, where appropriate, the booklets provide details of recommended further resources.Individual booklets in the series are available as PDF files below:

TRADD protein is an essential component of the RIG-like helicase antiviral pathway

Upon detection of viral RNA, the helicases RIG-I and/or MDA5 trigger, via their adaptor Cardif (also known as IPS-1, MAVS, or VISA), the activation of the transcription factors NF-kappaB and IRF3, which collaborate to induce an antiviral type I interferon (IFN) response. FADD and RIP1, known as mediators of death-receptor signaling, are implicated in this antiviral pathway; however, the link between death-receptor and antiviral signaling is not known. Here we showed that TRADD, a crucial adaptor of tumor necrosis factor receptor (TNFRI), was important in RIG-like helicase (RLH)-mediated signal transduction. TRADD is recruited to Cardif and orchestrated complex formation with the E3 ubiquitin ligase TRAF3 and TANK and with FADD and RIP1, leading to the activation of IRF3 and NF-kappaB. Loss of TRADD prevented Cardif-dependent activation of IFN-beta, reduced the production of IFN-beta in response to RNA viruses, and enhanced vesicular stomatitis virus replication. Thus, TRADD is not only an essential component of proinflammatory TNFRI signaling, but is also required for RLH-Cardif-dependent antiviral immune responses