Improved synchronous production of Plasmodium falciparum gametocytes in vitro.

The sexual stages of the Plasmodium falciparum life cycle are attractive targets for vaccines and transmission blocking drugs. Difficulties in culturing and obtaining large amounts of sexual stage P. falciparum parasites, particularly early stages, have often limited research progress in this area. We present a new protocol which simplifies the process of stimulating gametocytogenesis leading to improved synchronous gametocyte production. This new method can be adapted to enrich for early stage gametocytes (I and II) with a higher degree of purity than has previously been achieved, using MACS magnetic affinity columns. The protocol described lends itself to large scale culturing and harvesting of synchronous parasites suitable for biochemical assays, northern blots, flow cytometry, microarrays and proteomic analysis

Peripheral primitive neuroectodermal tumour - A rare cause of a popliteal fossa mass: A case report and review of the literature

A literature review of peripheral primitive neuroectodermal tumours, illustrated with an index case report describing an 80-year-old woman who presented with a mass in the left popliteal fossa, is reported. An excision biopsy was performed, revealing a possible peripheral primitive neuroectodermal tumour as the primary pathology. Normally confined to the chest wall and axial soft tissues of children and young adults, reports of this tumour existing in other areas and in the elderly population are scarce

Parvovirus 4 Infection and Clinical Outcome in High-Risk Populations

Parvovirus 4 (PARV4) is a DNA virus frequently associated with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections, but its clinical significance is unknown. We studied the prevalence of PARV4 antibodies in 2 cohorts of HIV- and HCV-infected individuals (n=469) and the correlations with disease status. We found that PARV4 infection frequently occurred in individuals exposed to bloodborne viruses (95% in HCV-HIV coinfected intravenous drug users [IDUs]). There were no correlations between PARV4 serostatus and HCV outcomes. There was, however, a significant association with early HIV-related symptoms, although because this was tightly linked to both HCV status and clinical group (IDU), the specific role of PARV4 is not yet clea

The molecular basis of malignant catarrhal fever

Alcelaphine herpesvirus-1 (A1HV-1) is gammaherpesvirus that can cause the devastating, fatal disease malignant catarrhal fever (MCF) in susceptible ruminant hosts but not in its natural host the blue wildebeest. Despite its scientific and economic importance little is known about the underlying molecular basis of MCF pathogenesis. The purpose of this study is to characterise four unique open reading frames (ORFs) of A1HV-1 and examine their contribution to viral pathogenesis. These ORFs are located at the left hand end of the genome, a region known to contain unique transforming and immunomodulatory genes in other gammaherpesviruses, and are predicted to encode two small gene products with no significant homology to any known proteins (ORF A1 and ORF A4), a transcription factor (ORF A2) and a member of the semaphorin family (ORF A3).A 6.2 Kb fragment from A1F1V-1 containing all four ORFs under their natural promoters was cloned into the left hand end region of murine gammaherpesvirus-76 (MHV-76). This allowed for the study of the in vivo contribution to pathogenesis of the gene products in a well characterised small animal model. The recombinant virus showed no difference in its ability to replicate in vitro. Viral titres and lung pathology in infected mice were also comparable although the A1HV-1 gene transcripts were detectable.The ORF A2 gene product expressed as a recombinant fusion protein in mammalian cells consistently showed nuclear localisation, supporting the prediction that this protein functions as a transcription factor. However, attempts to conclusively demonstrate transcriptional activity of this protein were unsuccessful

"Dead Wood" and Other Stories

My senior project consists of three short stories written during my junior year of college, although they’re the second or third rewrites of earlier, similar pieces going back to my freshman year. The first piece is set in the Taughannock gorge trails on the southwestern side of Cayuga lake, a place I’ve grown up hiking and exploring since I was a kid; the second in the Cornell University woods a halfmile up the road from my house, very close to where I learned to hunt; the third in one of the many abandoned or otherwise derelict plots of farmland in the rural outskirts of Tompkins County. Although I didn’t write them as a set, all three are loosely connected by motifs of pride and, necessarily, shame — causing the death of a friend, needlessly killing in a hunt, burning down your childhood home — as well as their physical proximity.Purchase College SUNYCreative WritingBachelor of ArtsPoochigian, Aaro

Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes.

Parasite-encoded variant surface antigens (VSAs) like the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA(SM) to identify PfEMP1 responsible for the VSA(SM) phenotype. Expression of VSA(SM) was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria

1 Cellular protein TTC4 and its cofactor HSP90 are pro-viral for bovine herpesvirus 1

Bovine Herpesvirus Type 1 (BoHV-1) infection causes infectious bovine rhinotracheitis and genital disease in cattle, with significant economic and welfare impacts. However, the role of cellular host factors during viral replication remains poorly characterised. A previously performed genome-wide CRISPR knockout screen identified pro- and antiviral host factors acting during BoHV-1 replication. Herein we validate a pro-viral role for a candidate from this screen: the cellular protein tetracopeptide repeat protein 4 (TTC4). We show that TTC4 transcript production is upregulated during BoHV-1 infection. Depletion of TTC4 protein impairs BoHV-1 protein production but does not reduce production of infectious virions, whereas overexpression of exogenous TTC4 results in a significant increase in production of infectious BoHV-1 virions. TTC4 itself is poorly characterized (especially in the context of virus infection), but is a known co-chaperone of heat shock protein 90 (HSP90). HSP90 has a well-characterized pro-viral role during the replication of diverse herpesviruses, and we therefore hypothesized that HSP90 is also pro-viral for BoHV-1. Drug-mediated inhibition of HSP90 using geldanamycin at sub-cytotoxic concentrations inhibited both BoHV-1 protein production and viral genome replication, indicating a pro-viral role for HSP90 during BoHV-1 infection. Our data demonstrates pro-viral roles for both TTC4 and HSP90 during BoHV-1 replication; possibly, interactions between these two proteins are required for optimal BoHV-1 replication, or the two proteins may have independent pro-viral roles

Nonprimate hepaciviruses in domestic horses, United kingdom

Although the origin of hepatitis C virus infections in humans remains undetermined, a close homolog of this virus, termed canine hepacivirus (CHV) and found in respiratory secretions of dogs, provides evidence for a wider distribution of hepaciviruses in mammals. We determined frequencies of active infection among dogs and other mammals in the United Kingdom. Samples from dogs (46 respiratory, 99 plasma, 45 autopsy samples) were CHV negative by PCR. Screening of 362 samples from cats, horses, donkeys, rodents, and pigs identified 3 (2%) positive samples from 142 horses. These samples were genetically divergent from CHV and nonprimate hepaciviruses that horses were infected with during 2012 in New York state, USA. Investigation of infected horses demonstrated nonprimate hepacivirus persistence, high viral loads in plasma (105–107 RNA copies/mL), and liver function test results usually within reference ranges, although several values ranged from high normal to mildly elevated. Disease associations and host range of nonprimate hepaciviruses warrant further investigation