261 research outputs found
Analysis of morepork vocalizations recorded using a permanently located mobile phone
The purpose of this work included the annotation of audio recordings of bird vocalizations to be used to train a machine learning algorithm to automatically detect bird calls. In addition, this work was intended to demonstrate the ability of The Cacophony Project’s mobile phone based ‘Bird Monitor’ for on-going monitoring of bird vocalizations.This work is important because it forms part of The Cacophony Project’s strategy to provide a low cost and robust means of collecting bird vocalization information to help determine the effectiveness of pest control activities. The main results show that the Bird Monitor does reliably capture bird calls over an extended period and can be used to create many annotated recordings from a real situation. It is concluded that the approach of choosing the distinct call of the Morepork as an entry into the area of automatic bird call counting was valid
Identification of a lysosomal pathway regulating degradation of the bone morphogenetic protein receptor type II.
Bone morphogenetic proteins (BMPs) are critically involved in early development and cell differentiation. In humans, dysfunction of the bone morphogenetic protein type II receptor (BMPR-II) is associated with pulmonary arterial hypertension (PAH) and neoplasia. The ability of Kaposi sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi sarcoma and primary effusion lymphoma, to down-regulate cell surface receptor expression is well documented. Here we show that KSHV infection reduces cell surface BMPR-II. We propose that this occurs through the expression of the viral lytic gene, K5, a ubiquitin E3 ligase. Ectopic expression of K5 leads to BMPR-II ubiquitination and lysosomal degradation with a consequent decrease in BMP signaling. The down-regulation by K5 is dependent on both its RING domain and a membrane-proximal lysine in the cytoplasmic domain of BMPR-II. We demonstrate that expression of BMPR-II protein is constitutively regulated by lysosomal degradation in vascular cells and provide preliminary evidence for the involvement of the mammalian E3 ligase, Itch, in the constitutive degradation of BMPR-II. Disruption of BMP signaling may therefore play a role in the pathobiology of diseases caused by KSHV infection, as well as KSHV-associated tumorigenesis and vascular disease
Diaspora Policies, Consular Services and Social Protection for German Citizens Abroad
This chapter presents an overview of German policies vis-Ã -vis German nationals living abroad. For the most part, the German Government does not reach out to or encourage engagement from or with German nationals living abroad. This is in contrast to a concerted cultural outreach to ethno-national German minorities in Central and Eastern Europe. Rights in Germany are largely residence-based, and access to rights is thus associated with (legal) residence in Germany, rather than with holding German citizenship. There are two clear exceptions: one is a robust system that enables voting from abroad for German citizens, and the other is facilitated access from abroad to pensions for years worked in Germany. With respect to other measures of social protections, no clear policy can be said to exist. Access to other forms of social protection is on the basis of exception, with consular officials exercising discretion in such cases
Biomarker panels associated with progression of renal disease in type 1 diabetes
AIMS/HYPOTHESIS:We aimed to identify a sparse panel of biomarkers for improving the prediction of renal disease progression in type 1 diabetes.METHODS:We considered 859 individuals recruited from the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) and 315 individuals from the Finnish Diabetic Nephropathy (FinnDiane) study. All had an entry eGFR between 30 and 75 ml min-1[1.73 m]-2, with those from FinnDiane being oversampled for albuminuria. A total of 297 circulating biomarkers (30 proteins, 121 metabolites, 146 tryptic peptides) were measured in non-fasting serum samples using the Luminex platform and LC electrospray tandem MS (LC-MS/MS). We investigated associations with final eGFR adjusted for baseline eGFR and with rapid progression (a loss of more than 3 ml min-1[1.73 m]-2 year-1) using linear and logistic regression models. Panels of biomarkers were identified using a penalised Bayesian approach, and their performance was evaluated through 10-fold cross-validation and compared with using clinical record data alone.RESULTS:For final eGFR, 16 proteins and 30 metabolites or tryptic peptides showed significant association in SDRNT1BIO, and nine proteins and five metabolites or tryptic peptides in FinnDiane, beyond age, sex, diabetes duration, study day eGFR and length of follow-up (all at p CONCLUSIONS/INTERPRETATION:Among a large set of associated biomarkers, a sparse panel of just CD27 and KIM-1 contains most of the predictive information for eGFR progression. The increment in prediction beyond clinical data was modest but potentially useful for oversampling individuals with rapid disease progression into clinical trials, especially where there is little information on prior eGFR trajectories</p
The Viral Interferon Regulatory Factors of Kaposi's Sarcoma-Associated Herpesvirus Differ in Their Inhibition of Interferon Activation Mediated by Toll-Like Receptor 3
Kaposi's sarcoma-associated herpesvirus (KSHV) infection is correlated with three human malignancies and can establish lifelong latent infection in multiple cell types within its human host. In order to establish and maintain infection, KSHV utilizes multiple mechanisms to evade the host immune response. One such mechanism is the expression of a family of genes with homology to cellular interferon (IFN) regulatory factors (IRFs), known as viral IRFs (vIRFs). We demonstrate here that KSHV vIRF1, -2, and -3 have a differential ability to block type I interferon signaling mediated by Toll-like receptor 3 (TLR3), a receptor we have previously shown to be activated upon KSHV infection. vIRF1, -2, and -3 inhibited TLR3-driven activation of IFN transcription reporters. However, only vIRF1 and vIRF2 inhibited increases in both IFN-β message and protein levels following TLR3 activation. The expression of vIRF1 and vIRF2 also allowed for increased replication of a virus known to activate TLR3 signaling. Furthermore, vIRF1 and vIRF2 may block TLR3-mediated signaling via different mechanisms. Altogether, this report indicates that vIRFs are able to block IFN mediated by TLRs but that each vIRF has a unique function and mechanism for blocking antiviral IFN responses
Prevalence of antibodies to human herpesvirus-8 in populations with and without risk for infection in São Paulo State
Cancers associated with Kaposi's sarcoma (KS) in AIDS: a link between KS herpesvirus and immunoblastic lymphoma
Kaposi's sarcoma (KS), common among persons with acquired immunodeficiency syndrome (AIDS), is caused by KS herpesvirus (KSHV) but whether KSHV causes other malignancies is uncertain. Using linked United States AIDS and cancer registries, we measured the incidence of specific malignancies in persons with AIDS (4–27 months after AIDS onset). We identified associations with KSHV by calculating a relative risk: cancer incidence in persons with KS (all were KSHV-infected) divided by incidence in persons without KS. Using Poisson regression, relative risks were adjusted for human immunodeficiency virus risk group, gender, age, race, and calendar year. We included 189 159 subjects (26 972 with KS). Immunoblastic lymphoma was significantly associated with KS (506 cases; relative risks: unadjusted 2.44, 95%CI 2.00–2.96, adjusted 1.58, 95%CI 1.29–1.93). Only one immunoblastic lymphoma had pleura as primary site. None of 37 other specified malignancies (other non-Hodgkin lymphomas, haematological malignancies, solid tumours) was significantly associated with KS. In summary, the association of immunoblastic lymphoma with KS was specific among examined malignancies and remained significant after statistical adjustment. Our findings, and the previously demonstrated presence of KSHV in the histologically related primary effusion lymphoma, suggest that KSHV is involved in the pathogenesis of some immunoblastic lymphomas. © 2001 Cancer Research Campaig
Reactive Oxygen Species Hydrogen Peroxide Mediates Kaposi's Sarcoma-Associated Herpesvirus Reactivation from Latency
Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent
infection in the host following an acute infection. Reactivation from latency
contributes to the development of KSHV-induced malignancies, which include
Kaposi's sarcoma (KS), the most common cancer in untreated AIDS patients,
primary effusion lymphoma and multicentric Castleman's disease. However,
the physiological cues that trigger KSHV reactivation remain unclear. Here, we
show that the reactive oxygen species (ROS) hydrogen peroxide
(H2O2) induces KSHV reactivation from latency through
both autocrine and paracrine signaling. Furthermore, KSHV spontaneous lytic
replication, and KSHV reactivation from latency induced by oxidative stress,
hypoxia, and proinflammatory and proangiogenic cytokines are mediated by
H2O2. Mechanistically, H2O2
induction of KSHV reactivation depends on the activation of mitogen-activated
protein kinase ERK1/2, JNK, and p38 pathways. Significantly,
H2O2 scavengers N-acetyl-L-cysteine (NAC), catalase
and glutathione inhibit KSHV lytic replication in culture. In a mouse model of
KSHV-induced lymphoma, NAC effectively inhibits KSHV lytic replication and
significantly prolongs the lifespan of the mice. These results directly relate
KSHV reactivation to oxidative stress and inflammation, which are physiological
hallmarks of KS patients. The discovery of this novel mechanism of KSHV
reactivation indicates that antioxidants and anti-inflammation drugs could be
promising preventive and therapeutic agents for effectively targeting KSHV
replication and KSHV-related malignancies
Gene expression profile of AIDS-related Kaposi's sarcoma
BACKGROUND: Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome. METHODS: In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results. RESULTS: The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages. CONCLUSION: The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages
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