Equine sarcoids, part 1: clinical presentation and epidemiology

Equine sarcoids are the most common skin tumors in horses and other equids. In their pathogenesis, the bovine papillomavirus (BPV) plays a major role. Many clinical manifestations have been described, ranging from small single lesions to multiple aggressively growing masses. Histopathologically, it is considered as a biphasic tumor with epidermal hyperplasia and subepidermal proliferation of transformed fibroblasts. The diagnosis can be made clinically, histopathologically and/or by detection of BPV DNA. Sarcoids can appear on any part of the body, but they are mostly localized on the ventral abdomen, the paragenital region, head and limbs. Sarcoids occur independent of breed, coat color, sex or age, but they develop more commonly in young adults and certain families and breeds are more vulnerable than others. Transmission of BPV is supposed to happen from cattle to horse or from horse to horse, possibly via insects

Equine sarcoids, part 3: association with bovine papillomavirus

The genetic material of the bovine papillomavirus (BPV) can be detected in virtually all equine sarcoids. Eight different types have been described, all inducing benign proliferation of epithelium in cattle. BPV-1 and -2 are less strictly species-specific and can induce equine sarcoids in horses. Historically, association between BPV and equine sarcoids has been demonstrated using inoculation studies and detection of BPV DNA and BPV gene expression. The BPV genome is composed of 6 early and 2 late genes, with E5 and E6 being the most important transforming genes. Specific BPV-1 variants associated with equine sarcoids have been reported, suggesting circulation of the virus between horses. In horses, a non-productive BPV infection occurs, with only transcription of early genes, responsible for genome maintenance, regulation of cell growth and cell transformation. There is no formation of new infectious virus particles as is the case in the natural host

Equine sarcoids, part 2: current treatment modalities

Treatment of sarcoids is often challenging, due to the variable clinical presentation of lesions and the frequent local recurrences. In this article, both the surgical and the non-surgical treatment of equine sarcoids are reviewed. It is generally accepted that the prognosis is worse if unsuccessful attempts have been made previously. Therefore, the best available treatment option should always be used at the first attempt of treatment. Different surgical approaches have been reported, including conventional excision, cryosurgery and CO2 laser surgery. Success rates are high if a non-touch approach, wide surgical margins and general anesthesia can be applied. Local chemotherapy is a valuable addition in the treatment of sarcoids and can be combined with surgery. Radiotherapy is a very successful treatment, but safety precautions prevent routine application. Local immunotherapy including Bacillus Calmette-Guerin vaccination and imiquimod cream are commonly applied treatments which induce rather effective tumour regression

The Transcriptional Repressor Kaiso Localizes at the Mitotic Spindle and Is a Constituent of the Pericentriolar Material

Kaiso is a BTB/POZ zinc finger protein known as a transcriptional repressor. It was originally identified through its in vitro association with the Armadillo protein p120ctn. Subcellular localization of Kaiso in cell lines and in normal and cancerous human tissues revealed that its expression is not restricted to the nucleus. In the present study we monitored Kaiso's subcellular localization during the cell cycle and found the following: (1) during interphase, Kaiso is located not only in the nucleus, but also on microtubular structures, including the centrosome; (2) at metaphase, it is present at the centrosomes and on the spindle microtubules; (3) during telophase, it accumulates at the midbody. We found that Kaiso is a genuine PCM component that belongs to a pericentrin molecular complex. We analyzed the functions of different domains of Kaiso by visualizing the subcellular distribution of GFP-tagged Kaiso fragments throughout the cell cycle. Our results indicate that two domains are responsible for targeting Kaiso to the centrosomes and microtubules. The first domain, designated SA1 for spindle-associated domain 1, is located in the center of the Kaiso protein and localizes at the spindle microtubules and centrosomes; the second domain, SA2, is an evolutionarily conserved domain situated just before the zinc finger domain and might be responsible for localizing Kaiso towards the centrosomal region. Constructs containing both SA domains and Kaiso's aminoterminal BTB/POZ domain triggered the formation of abnormal centrosomes. We also observed that overexpression of longer or full-length Kaiso constructs led to mitotic cell arrest and frequent cell death. Knockdown of Kaiso accelerated cell proliferation. Our data reveal a new target for Kaiso at the centrosomes and spindle microtubules during mitosis. They also strongly imply that Kaiso's function as a transcriptional regulator might be linked to the control of the cell cycle and to cell proliferation in cancer

NBPF1, a tumor suppressor candidate in neuroblastoma, exerts growth inhibitory effects by inducing a G1 cell cycle arrest

Background: NBPF1 (Neuroblastoma Breakpoint Family, member 1) was originally identified in a neuroblastoma patient on the basis of its disruption by a chromosomal translocation t(1;17)(p36.2;q11.2). Considering this genetic defect and the frequent genomic alterations of the NBPF1 locus in several cancer types, we hypothesized that NBPF1 is a tumor suppressor. Decreased expression of NBPF1 in neuroblastoma cell lines with loss of 1p36 heterozygosity and the marked decrease of anchorage-independent clonal growth of DLD1 colorectal carcinoma cells with induced NBPF1 expression further suggest that NBPF1 functions as tumor suppressor. However, little is known about the mechanisms involved. Methods: Expression of NBPF was analyzed in human skin and human cervix by immunohistochemistry. The effects of NBPF1 on the cell cycle were evaluated by flow cytometry. We investigated by real-time quantitative RT-PCR the expression profile of a panel of genes important in cell cycle regulation. Protein levels of CDKN1A-encoded p21(CIP1/WAF1) were determined by western blotting and the importance of p53 was shown by immunofluorescence and by a loss-offunction approach. LC-MS/MS analysis was used to investigate the proteome of DLD1 colon cancer cells with induced NBPF1 expression. Possible biological interactions between the differentially regulated proteins were investigated with the Ingenuity Pathway Analysis tool. Results: We show that NBPF is expressed in the non-proliferative suprabasal layers of squamous stratified epithelia of human skin and cervix. Forced expression of NBPF1 in HEK293T cells resulted in a G1 cell cycle arrest that was accompanied by upregulation of the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) in a p53-dependent manner. Additionally, forced expression of NBPF1 in two p53-mutant neuroblastoma cell lines also resulted in a G1 cell cycle arrest and CDKN1A upregulation. However, CDKN1A upregulation by NBPF1 was not observed in the DLD1 cells, which demonstrates that NBPF1 exerts cell-specific effects. In addition, proteome analysis of NBPF1-overexpressing DLD1 cells identified 32 differentially expressed proteins, of which several are implicated in carcinogenesis. Conclusions: We demonstrated that NBPF1 exerts different tumor suppressive effects, depending on the cell line analyzed, and provide new clues into the molecular mechanism of the enigmatic NBPF proteins

Downtown Waterville Feasibility Study Waterville, Maine

The Purpose and Need for this project is to: “Revitalize the Downtown to improve the aesthetics, support existing businesses and encourage economic growth, improve pedestrian and bicycle accommodations and provide adequate parking while maintaining vehicular capacity in the overall area.” Contributions and assistance in the completion of the study were provided by the City of Waterville, Colby College, the Maine Department of Transportation, and the General Public

Inflammatory monocytes regulate Th1 oriented immunity to CpG adjuvanted protein vaccines through production of IL-12

Due to their capacity to skew T cell responses towards Th1 oriented immunity, oligonucleotides containing unmethylated CpG motifs (CpG) have emerged as interesting adjuvants for vaccination. Whereas the signalling pathways in response to CpG mediated TLR9 activation have been extensively documented at the level of the individual cell, little is however known on the precise identity of the innate immune cells that govern T cell priming and polarisation to CpG adjuvanted protein antigens in vivo. In this study, we demonstrate that optimal induction of Th1 oriented immunity to CpG adjuvanted protein vaccines requires the coordinated actions of conventional DCs and of monocytes. Whilst conventional DCs were required for antigen presentation and initial T cell priming, monocytes constitute the main source of the Th1 polarising cytokine IL-12

Waarnemingen.be : non-native plant and animal occurrences in Flanders and the Brussels Capital Region, Belgium

Citizen scientists make important contributions to the collection of occurrence data of non-native species. We present two datasets comprising more than 520,000 records of 1,771 non-native species from Flanders and the Brussels Capital Region in Belgium, Western Europe, collected through the website http://www.waamemingen.be hosted by Stichting Natuurinformatie and managed by the nature conservation NGO Natuurpunt. Most records were collected by citizen scientists, mainly since 2008. Waarnemingen.be aims at recording all species, native and non-native, and it is shown here that this kind of biodiversity portals are also particularly well suited to collect large amounts of data on non-native species. Both datasets presented here are also discoverable through the Global Biodiversity Information Facility (GBIF)