A methodological framework to assess the socio-economic impact of underground quarries: A case study from Belgian Limburg.

This study developed a methodology to assess the socio-economic impact of the presence and collapse of underground limestone quarries. For this we rely on case study evidence from Riemst, a village located in Eastern Belgium and use both secondary and primary data sources. A sinkhole inventory as well as data about the prevention costs provided by the municipality was used. To estimate the recreational values of the quarries, visitor data was obtained from the tourist office of Riemst. Next, two surveys were conducted among inhabitants and four real estate agents and one notary. The direct and indirect damages were assessed using respectively the repair cost and production and real estate value losses. The total yearly direct and indirect damage equals €415000 (±€85000) and more than half of it can be attributed to the depreciation of real estate (€230000). The quarries have recreational, cultural-historical and ecological values and thus generate societal benefits. The yearly recreational value was at least €613000 in 2012 values. The ecological and cultural-historical values augment to €180000 per year (in 2012 values). Further, our study indicates that the gains from filling up the quarries below the houses located above an underground limestone quarry outweigh the costs in the case study area. The net gain from filling up the underground quarry ranges €38700 to €101700 per house. This is only the lower bound of the net gain from filling up these underground quarries since preventive filling makes future collapses less likely so that future direct repair costs will be most likely smaller.

Cutaneous Mycobacterium chelonae infection in Edinburgh and the Lothians, South-East Scotland, U.K.

BACKGROUND: We reviewed all cases of Mycobacterium chelonae infection seen in our department between 1 January 2008 and 31 December 2012. OBJECTIVES: To review the epidemiology, clinical features and management of cutaneous M. chelonae in South-East Scotland, and to compare prevalence data with the rest of Scotland. METHODS: The Scottish Mycobacteria Reference Laboratory database was searched for all cases of cutaneous mycobacterial infections. RESULTS: One hundred and thirty-four cases of cutaneous mycobacterial infection were recorded. Sixty-three were tuberculous; of the remaining 71, M. chelonae was the most common nontuberculous organism (27 cases). National Health Service (NHS) Lothian Health Board was the area with highest incidence in the Scotland (12 cases). Three main groups of patients in the NHS Lothian Health Board contracted M. chelonae: immunosuppressed patients (n = 6); those who had undergone tattooing (n = 4); and others (n = 2). One case is, we believe, the first report of M. chelonae cutaneous infection associated with topical corticosteroid immunosuppression. The majority of patients were treated with clarithromycin monotherapy. CONCLUSION: The most prevalent nontuberculous cutaneous mycobacterial organism in Scotland is M. chelonae. The prevalence of M. chelonae in Edinburgh and the Lothians compared with the rest of Scotland is disproportionately high, possibly owing to increased local awareness and established facilities for mycobacterial studies. Immunosuppression with prednisolone appears to be a major risk factor. The first outbreak of tattoo-related M. chelonae infection in the U.K. has been reported. Clinicians should be aware of mycobacterial cutaneous infection and ensure that diagnostic skin samples are cultured at the optimal temperatures.

Mycobacterium chelonae infection: a complication of tattooing.

We describe an outbreak of Mycobacterium chelonae infection in four young immunocompetent patients who were tattooed by the same artist. All had been previously tattooed without complication, but following the latest tattooing session, they all developed a very similar papular eruption confined to skin that had been newly coloured light grey. On histological examination of the eruption, granulomatous inflammation with microabscess formation was seen, in association with the tattoo pigment. Skin cultures grown under optimal conditions grew M. chelonae, sensitive to clarithromycin, from one patient. M. chelonae was also cultured from the contents and nozzle of an opened bottle of light-grey ink from the tattoo parlour frequented by the patients. Dermatologists should consider mycobacterial infection in patients who develop inflammatory changes within a new tattoo.

Auger-mediated sticking of positrons to surfaces: evidence for a single-step transition from a scattering state to a surface image potential bound state.

We present the observation of an efficient mechanism for positron sticking to surfaces termed here Auger-mediated sticking. In this process the energy associated with the positrons transition from an unbound scattering state to a bound image potential state is coupled to a valence electron which can then have sufficient energy to leave the surface. Compelling evidence for this mechanism is found in a narrow secondary electron peak observed at incident positron kinetic energies well below the electron work function.

Adherence to topical dermatological therapy: lessons from oral drug treatment.

Patients are remarkably nonadherent to medical treatment regimens across all diseases and classes of therapy, and it has been estimated that nonadherence to drug treatment is responsible for as many as 10% of all hospital admissions. Nonadherence to treatment also has significant negative effects on treatment outcomes across a wide range of diseases. Patient-related factors such as age, ethnicity, literacy (including health literacy), health beliefs, and socioeconomic conditions have been shown to influence adherence to oral therapy. Medication-related factors, such as regimen complexity and duration of treatment, also impact on adherence. Variables that significantly influence adherence to oral drugs have similar effects on adherence to topical therapy. Both educational and psychological interventions along with simplification of dosing regimens can significantly improve adherence to oral therapy and limited evidence indicates that these approaches are also effective in patients receiving topical therapy. There is very little information about the effects of dosing regimens on adherence to topical medical therapy. The advent of new drug formulations that permit once-daily or single-dose drug application will, however, permit evaluation of different topical treatment regimens on adherence and treatment outcomes in patients with dermatological disease.

Overexpression of MBNL1 fetal isoforms and modified splicing of Tau in the DM1 brain: two individual consequences of CUG trinucleotide repeats.

Neurofibrillary degeneration is often observed in the brain of patients with type 1 myotonic dystrophy (DM1). It consists principally of the aggregation of Tau isoforms that lack exon 2/3 encoded sequences, and is the consequence of the modified splicing of Tau pre-mRNA. In experimental models of DM1, the splicing of several transcripts is modified due to the loss of Muscleblind-like 1 (MBNL1) function. In the present study, we demonstrate that the MBNL1 protein is also present in the human brain, and consists of several isoforms, as shown by RT-PCR and sequencing. In comparison with controls, we show that the adult DM1 brain exhibits modifications in the splicing of MBNL1, with the preferential expression of long MBNL1 isoforms--a splicing pattern similar to that seen in the fetal human brain. In cultured HeLa cells, the presence of long CUG repeats, such as those found in the DM1 mutation, leads to similar changes in the splicing pattern of MBNL1, and the localization of MBNL1 in nuclear RNA foci. Long CUG repeats also reproduce the repression of Tau exon 2/3 inclusion, as in the human disease, suggesting that their effect on MBNL1 expression may lead to changes in Tau splicing. However, while an overall reduction in the expression of MBNL1 mimics the effect of the DM1 mutation, none of the MBNL1 isoforms tested so far modulates the endogenous splicing of Tau. The modified splicing of Tau thus results from a possibly CUG-mediated loss of function of MBNL1, but not from changes in the MBNL1 expression pattern.

Energy- and momentum-resolved exchange and spin-orbit interaction in cobalt film by spin-polarized two-electron spectroscopy.

Spontaneous ordering of electronic spins in ferromagnetic materials is one of the best known and most studied examples of quantum correlations. Exchange correlations are responsible for long range spin order and the spin-orbit interaction (SOI) can create preferred crystalline directions for the spins, i.e., magnetic anisotropy. Presented experimental data illustrate how novel spin-polarized two-electron spectroscopy in-reflection mode allows observation of the localization of spin-dependent interactions in energy-momentum space. Comparison of spin-orbit asymmetries in spectra of Co film and clean W(110) may indicate the presence of interface specific proximity effects providing important clues to the formation of preferred orientations for the magnetic moment of the Co film. These results may help to understand the microscopic origin of interface magnetic anisotropy.

MEF2-mediated recruitment of class II HDAC at the EBV immediate early gene BZLF1 links latency and chromatin remodeling.

In B lymphocytes induced to proliferate in vitro by the Epstein-Barr virus (EBV), extra-chromosomal viral episomes packaged in chromatin persist in the nucleus, and there is no productive cycle. A switch from this latency to the productive cycle is observed after induced expression of the EBV BZLF1 gene product, the transcription factor EB1. We present evidence that, during latency, proteins of the myocyte enhancer binding factor 2 (MEF2) family are bound to the BZLF1 promoter and recruit class II histone deacetylases. Furthermore, we propose that latency is determined primarily by a specific and local recruitment of class II histone deacetylase (HDAC) by MEF2D to the BZLF1 gene promoter. The switch from latency to the productive cycle could be due in part to post-translational modification of MEF2 proteins and changes in the local acetylation state of the chromatin.

Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma.

Kaposi's sarcoma-associated herpesvirus (KSHV) is present in all epidemiologic forms of Kaposi's sarcoma (KS). The KSHV genome contains several open reading frames which are potentially implicated in the development of KS. Some are unique to KSHV; others are homologous to cellular genes. The putative role of these genes in the genesis of KS is discussed.

Characterization of the epstein-barr virus BRRF1 gene, located between early genes BZLF1 and BRLF1.

The switch from latency to a productive cycle in Epstein-Barr virus (EBV)-infected B cells proliferating in vitro is thought to be due to the transcriptional activation of two viral genes, BZLF1 and BRLF1, encoding two transcription factors called EB1 and R respectively. However, a third gene, BRRF1 is contained in the BZLF1/BRLF1 locus, overlapping with BRLF1 but in inverse orientation. We have characterized the 5' end of the BRRF1 mRNA and the promoter, PNa, at which BRRF1 pre-mRNA is initiated. We show that although a single BRRF1 mRNA species is induced by 12-O-tetradecanoylphorbol 13-acetate/sodium butyrate in several EBV-infected B cell lines, in Akata cells treated with anti-IgG two BRRF1 mRNAs can be detected. Transcription initiated at the BRRF1 promoter was activated by EB1 but not by R, and EB1-binding sites which contribute to the EB1-activated transcription have been mapped to between positions -469 and +1. A 34 kDa protein could be translated from the BRRF1 mRNA both in vitro and in vivo, and was found predominantly in the nucleus of HeLa cells transfected with a BRRF1 expression vector. Thus there are three promoters in the region of the EBV chromatin containing the BZLF1/BRLF1 genes, two of which, PZ and PNa, potentially share regulatory elements.

Epstein-Barr virus EB2 protein exports unspliced RNA via a Crm-1-independent pathway.

Human herpesviruses encode posttranscriptional activators that are believed to up-regulate viral replication by facilitating early and late gene expression. We have reported previously that the Epstein-Barr virus protein EB2 (also called M or SM) promotes nuclear export of RNAs that are poor substrates for spliceosome assembly, an effect that closely resembles the human immunodeficiency virus type 1 Rev-dependent nuclear export of unspliced viral RNA. Here we present experimental data showing that EB2 efficiently promotes the nuclear export of unspliced RNA expressed from a Rev reporter construct. Site-directed mutagenesis as well as domain swapping experiments indicate that a leucine-rich region found in the EB2 protein, which matches the consensus sequence for the leucine-rich nuclear export signal, is not a nuclear export signal per se. Accordingly, leptomycin B (LMB), a specific Crm-1 inhibitor, impairs Rev- but not EB2-dependent nuclear export of unspliced RNA. Moreover, EB2 nucleocytoplasmic shuttling visualized by a heterokaryon assay is, unlike Rev shuttling, not affected by LMB. We also show that overexpression of an N-terminal deletion mutant of Nup214/can, a major nucleoporin of the nuclear pore complex involved in several aspects of nuclear transport, blocks both Rev- and EB2-dependent nuclear export of RNA. These results strongly suggest that EB2 nuclear export of unspliced RNA is mediated by a Crm-1-independent pathway.

The herpes simplex virus 1 Us11 protein cooperates with suboptimal amounts of human immunodeficiency virus type 1 (HIV-1) Rev protein to rescue HIV-1 production.

The human immunodeficiency virus type 1 (HIV-1) RNA-binding Rev protein governs the expression of structural and enzymatic viral proteins at a posttranscriptional level. Binding of Rev to the stem-loop IIB (SLIIB) sequence of the Rev-response element (RRE) within unspliced and singly spliced viral mRNAs and to the nuclear export signal-binding receptor, hCRM1 (or exportin 1), is required for the export of these transcripts to the cytoplasm. We have previously shown that herpes simplex virus type 1 (HSV-1) RNA-binding Us11 protein is able to bind the RRE and substitute for Rev in inducing the expression of HIV-1 envelope glycoproteins. We show here that Us11 cannot substitute for Rev in rescuing a rev-deleted HIV-1 provirus. However, HIV-1 production is observed when Us11 is expressed with suboptimal amounts of Rev. An in vivo RNA-protein binding assay indicates that Us11 is unable to directly interact with the SLIIB RNA but can bind Rev assembled on that stem-loop structure. This association of US11 with Rev, which was confirmed by in vivo coimmunoprecipitation and GST-pulldown assays, therefore underlies a biological Us11-Rev cooperation. Furthermore this cooperation was shown to remain susceptible to the effect of leptomycin B, which blocks the binding of hCRM1 to the nuclear export signal of Rev. These observations performed with intron-containing constructs provide evidence that HSV-1 Us11 protein is not directly involved in the cytoplasmic accumulation of viral mRNAs but may be rather acting as an auxiliary protein, thus allowing this retroviral protein to fulfill the nuclear export of these transcripts and to rescue HIV-1 production.