Deletion of hypothetical wall teichoic acid ligases in Staphylococcus aureus activates the cell wall stress response.

The Staphylococcus aureus cell wall stress stimulon (CWSS) is activated by cell envelope-targeting antibiotics or depletion of essential cell wall biosynthesis enzymes. The functionally uncharacterized S. aureus LytR-CpsA-Psr (LCP) proteins, MsrR, SA0908 and SA2103, all belong to the CWSS. Although not essential, deletion of all three LCP proteins severely impairs cell division. We show here that VraSR-dependent CWSS expression was up to 250-fold higher in single, double and triple LCP mutants than in wild type S. aureus in the absence of external stress. The LCP triple mutant was virtually depleted of wall teichoic acids (WTA), which could be restored to different degrees by any of the single LCP proteins. Subinhibitory concentrations of tunicamycin, which inhibits the first WTA synthesis enzyme TarO (TagO), could partially complement the severe growth defect of the LCP triple mutant. Both of the latter findings support a role for S. aureus LCP proteins in late WTA synthesis, as in Bacillus subtilis where LCP proteins were recently proposed to transfer WTA from lipid carriers to the cell wall peptidoglycan. Intrinsic activation of the CWSS upon LCP deletion and the fact that LCP proteins were essential for WTA-loading of the cell wall, highlight their important role(s) in S. aureus cell envelope biogenesis.

Ultrastructural, Antigenic and Physicochemical Characterization of the Mojuí dos Campos (Bunyavirus) Isolated from Bat in the Brazilian Amazon Region

The Mojuí dos Campos virus (MDCV) was isolated from the blood of an unidentified bat (Chiroptera) captured in Mojuí dos Campos, Santarém, State of Pará, Brazil, in 1975 and considerated to be antigenically different from other 102 arboviruses belonging to several antigenic groups isolated in the Amazon region or another region by complement fixation tests. The objective of this work was to develop a morphologic, an antigenic and physicochemical characterization of this virus. MDCV produces cytopathic effect in Vero cells, 24 h post-infection (p.i), and the degree of cellular destruction increases after a few hours. Negative staining electron microscopy of the supernatant of Vero cell cultures showed the presence of coated viral particles with a diameter of around 98 nm. Ultrathin sections of Vero cells, and brain and liver of newborn mice infected with MDCV showed an assembly of the viral particles into the Golgi vesicles. The synthesis kinetics of the proteins for MDCV were similar to that observed for other bunyaviruses, and viral proteins could be detected as early as 6 h p.i. Our results reinforce the original studies which had classified MDCV in the family Bunyaviridae, genus Bunyavirus as an ungrouped virus, and it may represent the prototype of a new serogroup.

New nonculture-based methods for the diagnosis of invasive candidiasis.

PURPOSE OF REVIEW: Invasive candidiasis is a severe infectious complication occurring mostly in onco-hematologic and surgical patients. Its conventional diagnosis is insensitive and often late, leading to a delayed treatment and a high mortality. The purpose of this article is to review recent contributions in the nonconventional diagnostic approaches of invasive candidiasis, both for the detection of the epidose and the characterization of the etiologic agent. RECENT FINDINGS: Antigen-based tests to detect invasive candidiasis comprise a specific test, mannan, as well as a nonspecific test, beta-D-glucan. Both have a moderate sensitivity and a high specificity, and cannot be recommended alone as a negative screening tool or a positive syndrome driven diagnostic tool. Molecular-based tests still have not reached the stage of rapid, easy to use, standardized tests ideally complementing blood culture at the time of blood sampling. New tests (fluorescence in-situ hybridization or mass spectrometry) significantly reduce the delay of identification of Candida at the species level in positive blood cultures, and should have a positive impact on earlier appropriate antifungal therapy and possibly on outcome. SUMMARY: Both antigen-based and molecular tests appear as promising new tools to complement and accelerate the conventional diagnosis of invasive candidiasis with an expected significant impact on earlier and more focused treatment and on prognosis.

Quality and Fairness - A Health System for You

Over the last four years health services in Ireland have benefited from the largest ever sustained increase in funding. Facilities are being developed and refurbished, more staff are being hired and the number of people benefiting from health services has increased substantially. A lot has been achieved, but a lot remains to be done. Very clear deficiencies in services remain which must be addressed. There are unacceptably long waiting times in various parts of the system, important services remain underdeveloped and major demographic challenges must be addressed. By doubling health funding over the last four years, the Government has moved the debate on health funding from resources alone to both resources and reform. Download the Report here

National Drugs Strategy 2001 - 2008

In April 2000, the Cabinet Committee on Social Inclusion requested that a review of the current national drugs strategy be undertaken. The overall objective of the review was to identify any gaps or deficiencies in the existing strategy and to develop revised strategies and, if necessary, new arrangements through which to deliver them. A sub-group of the Inter-Departmental Group on Drugs and the National Drugs Strategy Team â?" known as the Review Group â?" managed and oversaw the process. As part of the review, a study of the latest available data on the extent andnature of drug misuse in Ireland was undertaken. This revealed that the most commonly used drug in Ireland is cannabis, followed by ecstasy. However, in terms of harm to the individual and the community, heroin has the greatest impact. Download the Report here

Loss of single HLA class I allospecificities in melanoma cells due to selective genomic abbreviations.

Expression of human leucocyte antigen (HLA) Class I molecules is essential for the recognition of malignant melanoma (MM) cells by CD8(+) T lymphocytes. A complete or partial loss of HLA Class I molecules is a potent strategy for MM cells to escape from immunosurveillance. In 2 out of 55 melanoma cell cultures we identified a complete phenotypic loss of HLA allospecificities. Both patients have been treated unsuccessfully with HLA-A2 peptides. To identify the reasons underlying the loss of single HLA-A allospecificities, we searched for genomic alterations at the locus for HLA Class I alpha-chain on chromosome 6 in melanoma cell cultures established from 2 selected patients with MM in advanced stage. This deficiency was associated with alterations of HLA-A2 gene sequences as determined by polymerase chain reaction-sequence specific primers (PCR-SSP). Karyotyping revealed a chromosomal loss in Patient 1, whereas melanoma cell cultures established from Patient 2 displayed 2 copies of chromosome 6. Loss of heterozygosity (LOH) using markers located around position 6p21 was detected in both cases. By applying group-specific primer-mixes spanning the 5'-flanking region of the HLA-A2 gene locus the relevant region was amplified by PCR and subsequent sequencing allowed alignment with the known HLA Class I reference sequences. Functional assays using HLA-A2-restricted cytotoxic T-cell clones were performed in HLA-A2 deficient MM cultures and revealed a drastically reduced susceptibility to CTL lysis in HLA-A2 negative cells. We could document the occurrence of selective HLA-A2 deficiencies in cultured advanced-stage melanoma metastases and identify their molecular causes as genomic alterations within the HLA-A gene locus.

Bats of Borneo: diversity, distributions and representation in protected areas

Protected areas are valuable in conserving tropical biodiversity, but an insufficient understanding of species diversity and distributions makes it difficult to evaluate their effectiveness. This is especially true on Borneo, a species rich island shared by three countries, and is particularly concerning for bats, a poorly known component of mammal diversity that may be highly susceptible to landscape changes. We reviewed the diversity, distributions and conservation status of 54 bat species to determine the representation of these taxa in Borneo's protected areas, and whether these reserves complement each other in terms of bat diversity. Lower and upper bound estimates of bat species composition were characterised in 23 protected areas and the proposed boundaries of the Heart of Borneo conservation area. We used lower and upper bound estimates of species composition. By using actual inventories, species representation was highly irregular, and even if some reserves were included in the Heart of Borneo, the protected area network would still exhibit low complementarity. By inferring species presence from distributions, composition between most reserves was similar, and complementarity was much higher. Predicting species richness using abundance information suggested that bat species representation in reserves may lie between these two extremes. We recommend that researchers better sample biodiversity over the island and address the conservation threats faced in Borneo both within and outside protected areas. While the Heart of Borneo Initiative is commendable, it should not divert attention from other conservation areas.

Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis.

Mycobacterium tuberculosis-specific cytolytic activity is mediated mostly by CD4+CTL in humans. CD4+CTL kill infected target cells by inducing Fas (APO-1/CD95)-mediated apoptosis. We have examined the effect of Fas ligand (FasL)-induced apoptosis of human macrophages infected in vitro with M. tuberculosis on the viability of the intracellular bacilli. Human macrophages expressed Fas and underwent apoptosis after incubation with soluble recombinant FasL. In macrophages infected either with an attenuated (H37Ra) or with a virulent (H37Rv) strain of M. tuberculosis, the apoptotic death of macrophages was associated with a substantial reduction in bacillary viability. TNF-induced apoptosis of infected macrophages was coupled with a similar reduction in mycobacterial viability, while the induction of nonapoptotic complement-induced cell death had no effect on bacterial viable counts. Infected macrophages also showed a reduced susceptibility to FasL-induced apoptosis correlating with a reduced level of Fas expression. These data suggest that apoptosis of infected macrophages induced through receptors of the TNF family could be an immune effector mechanism not only depriving mycobacteria from their growth environment but also reducing viable bacterial counts by an unknown mechanism. On the other hand, interference by M. tuberculosis with the FasL system might represent an escape mechanism of the bacteria attempting to evade the effect of apoptosis.

Característiques dels Generadors de Codi

Aquest estudi permet tenir una visió de les possibilitats reals dels generadors de codi, les seves característiques més destacades i les seves mancances. Finalment s'inclou una proposta de millora per incorporar als generadors de codi.

A Grounded Theory Model of the Counselling Referral Process in Primary Care Methadone Treatment in Ireland.

In terms of the treatment of illicit drug abuse, methadone maintenance is a well researched and widely applied systematic response. The approach to primary care methadone treatment in Ireland is based on the methadone protocol. Primary care plays a central role in the delivery of methadone treatment. Beginning with a view that a system evolves within the constraints and influencing factors of its context, the aim of this thesis is to model the process that has developed by which patients on primary care methadone treatment are referred to counselling. It investigates the role primary care practitioners perceive they have in relation to managing the psychosocial aspects of the methadone patient's treatment regime. It analyzes individual medical practitioner counselling referral mechanisms to determine what common processes operate across different practitioners. It identifies the factors that influence the use of counselling on primary care methadone programmes and structures these in a cause/effect model. This research used interviews and documentary analysis to acquire grounded data. The sample consisted primarily of medical practitioners involved in the delivery of methadone programmes. Others closely involved in the implementation of drug treatment in the primary care context made up the balance of interviewees. The study used a grounded theory methodology to induce the process that was latent in the grounded data. Concepts emerging were grouped under the headings of referral factors, decision making factors and factors related to the unique positioning of primary care at the interface between medicine and society. The core finding was that, in primary care in Ireland, there is no psychological model to complement the pharmacological intervention of methadone substitution. The findings from this study offer insight into the factors at work and their impacts, in the context of the use of counselling in primary care methadone treatment. The study suggests a possible direction for further evolution of opiate abuse treatment in Ireland which would transform it from a harm reduction to a holistic patient centric paradigm.This resource was contributed by The National Documentation Centre on Drug Use.

Detecting nanoscale vibrations as signature of life.

The existence of life in extreme conditions, in particular in extraterrestrial environments, is certainly one of the most intriguing scientific questions of our time. In this report, we demonstrate the use of an innovative nanoscale motion sensor in life-searching experiments in Earth-bound and interplanetary missions. This technique exploits the sensitivity of nanomechanical oscillators to transduce the small fluctuations that characterize living systems. The intensity of such movements is an indication of the viability of living specimens and conveys information related to their metabolic activity. Here, we show that the nanomotion detector can assess the viability of a vast range of biological specimens and that it could be the perfect complement to conventional chemical life-detection assays. Indeed, by combining chemical and dynamical measurements, we could achieve an unprecedented depth in the characterization of life in extreme and extraterrestrial environments.

TFC Redes de computadores : filtro de páginas web

Aquest treball final de carrera consisteix en la creació d'un complement que afegeix noves característiques a un navegador conegut com Firefox produït i proporcionat pel Projecte Mozilla. Aquest projecte desenvolupa, implementa i promou el programari lliure. El complement consisteix en un filtre de pàgines web a nivell de contingut.

Ethnicity Coding

The incidence, prevalence, and mortality of many diseases are known to vary by ethnic group.There are well documented inequities in access to prevention, treatment, and palliative health and social care services based on ethnic group. There are, too, reported differences in the quality of services received by different ethnic groups and of outcomes of treatment and care. Many of these inequities are amenable to change. However, in order to address them they must, first of all, be comprehensively defined and documented. Mainstreaming ethnic monitoring/data collection is a vital step in the process. The history of such data collection in the NHS is poor, whichever of the key datasets is examined: hospital episode statistics, general practitioner data, cancer registrations, and disease registers. While steps are now being taken to remedy some of these deficiencies, the continued non-availability of ethnic monitoring data and in some cases of compatible ethnically-coded denominator data remains a problem. In particular the lack of ethnic group in births and deaths data has been the subject of widespread comment by specialists in demography and public health and is probably the single action that could most improve the evidence based for addressing ethnic/racial inequalities in health and health care.

Estudi d'eines CASE que suporten OCLper a la generació automàtica de codi Java

Es tracta d'una recerca d'eines CASEque actualment suporten OCL en la generació automàtica de codi Java per estudiar-les ianalitzar-les a través d'un model de proves consistent en un diagrama de classes del modelestàtic de l'UML i una mostra variada d'instruccions OCL, amb l'objectiu de detectar lesseves mancances, analitzant el codi obtingut i determinar si controla o no cada tipus derestricció, i si s'han implementat bé en el codi.

Briefing 24: NCMP data 2008/9, East of England: Data quality

One in a series of six data briefings based on regional-level analysis of data from the National Child Measurement Programme (NCMP) undertaken by the National Obesity Observatory (NOO). The briefings are intended to complement the headline results for the region published in January 2010. This briefing covers issues relating to the quality and completeness of the NCMP data. Detailed analysis of the NCMP at national level is available from NOO at http://www.noo.org.uk/NOO_pubInformation on the methods used to