HYPOFIBRINOGENAEMIA

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Cytokinesis is blocked in mammalian cells transfected with Chlamydia trachomatis gene CT223

<p>Abstract</p> <p>Background</p> <p>The chlamydiae alter many aspects of host cell biology, including the division process, but the molecular biology of these alterations remains poorly characterized. Chlamydial inclusion membrane proteins (Incs) are likely candidates for direct interactions with host cell cytosolic proteins, as they are secreted to the inclusion membrane and exposed to the cytosol. The <it>inc </it>gene <it>CT223 </it>is one of a sequential set of orfs that encode or are predicted to encode Inc proteins. CT223p is localized to the inclusion membrane in all tested <it>C. trachomatis </it>serovars.</p> <p>Results</p> <p>A plasmid transfection approach was used to examine the function of the product of <it>CT223 </it>and other Inc proteins within uninfected mammalian cells. Fluorescence microscopy was used to demonstrate that <it>CT223</it>, and, to a lesser extent, adjacent <it>inc </it>genes, are capable of blocking host cell cytokinesis and facilitating centromere supranumeracy defects seen by others in chlamydiae-infected cells. Both phenotypes were associated with transfection of plasmids encoding the carboxy-terminal tail of CT223p, a region of the protein that is likely exposed to the cytosol in infected cells.</p> <p>Conclusion</p> <p>These studies suggest that certain Inc proteins block cytokinesis in <it>C. trachomatis</it>-infected cells. These results are consistent with the work of others showing chlamydial inhibition of host cell cytokinesis.</p

Dynamic electoral competition with voter loss-aversion and imperfect recall

This paper explores the implications of voter loss-aversion and imperfect recall for the dynamics of electoral competition in a simple Downsian model of repeated elections. The interplay between the median voter’s reference point and political parties’ choice of platforms generates a dynamic process of (de)polarization, following an initial shift in party ideology. This is consistent with the gradual nature of long-term trends in polarization in the US Congress

Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond

In the past four decades, chemoprevention of colorectal cancer (CRC) has been the subject of many epidemiologic and intervention trials of naturally occurring or pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as a viable option in this context was a major breakthrough; however, it was hampered by adverse cardiovascular events. This review questions whether chemopreventive measures for CRC are ready to be used in mass or individual applications, standing alone or in combination with other CRC-preventive measures. It also discusses steps that may be undertaken to explore this field further

Performance of typical and superior face recognisers on a novel interactive face matching procedure

Unfamiliar simultaneous face matching is error prone. Reducing incorrect identification decisions will positively benefit forensic and security contexts. The absence of view-independent information in static images likely contributes to the difficulty of unfamiliar face matching. We tested whether a novel interactive viewing procedure that provides the user with 3D structural information as they rotate a facial image to different orientations would improve face matching accuracy. We tested the performance of ‘typical’ (Experiment 1) and ‘superior’ (Experiment 2) face recognisers, comparing their performance using high quality (Experiment 3) and pixelated (Experiment 4) Facebook profile images. In each trial, participants responded whether two images featured the same person with one of these images being either a static face, a video providing orientation information, or an interactive image. Taken together, the results show that fluid orientation information and interactivity prompt shifts in criterion and support matching performance. Because typical and superior face recognisers both benefited from the structural information provided by the novel viewing procedures, our results point to qualitatively similar reliance on pictorial encoding in these groups. This also suggests that interactive viewing tools can be valuable in assisting face matching in high performing practitioner groups

Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection

<p>Abstract</p> <p>Background</p> <p>Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC) virus infection and fibrosis.</p> <p>Methods</p> <p>Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1) and 23 with advanced fibrosis (F3, F4) were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups.</p> <p>Results</p> <p>Seven individual protein spots were identified as either significantly increased (α₂-macroglobulin, haptoglobin, albumin) or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV) with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α₂-macroglobulin, are included in existing non-invasive serum marker panels.</p> <p>Conclusion</p> <p>Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.</p

Intracellular Bacteria Encode Inhibitory SNARE-Like Proteins

Pathogens use diverse molecular machines to penetrate host cells and manipulate intracellular vesicular trafficking. Viruses employ glycoproteins, functionally and structurally similar to the SNARE proteins, to induce eukaryotic membrane fusion. Intracellular pathogens, on the other hand, need to block fusion of their infectious phagosomes with various endocytic compartments to escape from the degradative pathway. The molecular details concerning the mechanisms underlying this process are lacking. Using both an in vitro liposome fusion assay and a cellular assay, we showed that SNARE-like bacterial proteins block membrane fusion in eukaryotic cells by directly inhibiting SNARE-mediated membrane fusion. More specifically, we showed that IncA and IcmG/DotF, two SNARE-like proteins respectively expressed by Chlamydia and Legionella, inhibit the endocytic SNARE machinery. Furthermore, we identified that the SNARE-like motif present in these bacterial proteins encodes the inhibitory function. This finding suggests that SNARE-like motifs are capable of specifically manipulating membrane fusion in a wide variety of biological environments. Ultimately, this motif may have been selected during evolution because it is an efficient structural motif for modifying eukaryotic membrane fusion and thus contribute to pathogen survival

Inflammatory pseudotumor of the liver: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Inflammatory pseudotumor of the liver represents a fairly uncommon pathology. Although it is a benign tumor, the correct diagnosis can be missed.</p> <p>Case presentation</p> <p>We report the case of a 55-year-old Caucasian man, who presented with a one-month history of abdominal pain and weight loss. He was diagnosed with a primary liver tumor by computed tomography and magnetic resonance imaging. Alpha-fetoprotein levels ranged within normal limits. A right posterior sectorectomy was performed. Histopathology revealed an inflammatory pseudotumor of the liver. Our patient remains in good condition one year later.</p> <p>Conclusion</p> <p>Although inflammatory pseudotumor of the liver is usually a benign process, controversy regarding its management still exists. With this case report we review the existing literature and consider hepatectomy as a safe treatment approach.</p

A randomized, double blind, placebo and active comparator controlled pilot study of UP446, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin

<p>Abstract</p> <p>Background</p> <p>Current use of prescribed or over the counter non-steroidal anti-inflammatory drugs (NSAIDs) for pain and osteoarthritis (OA) have untoward gastrointestinal and cardiovascular related side effects, as a result the need for a safe and effective alternative has become unequivocally crucial.</p> <p>Method</p> <p>A randomized, double blind, placebo and active controlled pilot study of a novel dual pathway, COX1/2 and LOX, inhibitor anti-inflammatory agent of botanical origin, UP446 was conducted. Sixty subjects (age 40-75) with symptomatic OA of the hip or knee were assigned to 4 treatment groups (n = 15); Group A0 (Placebo, CMC capsule), Group A1 (UP446 250 mg/day), Group A2 (UP446 500 mg/day) and Group A3 (Celecoxib, 200 mg/day). MOS-SF-36 and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) data were collected at baseline and after 30, 60 and 90 days of treatment as a measure of efficacy. Erythrocyte sedimentation rate, C-reactive protein, plasma thrombin time (PTT), fructosamine, Hematology, clinical chemistry and fecal occult blood were monitored for safety.</p> <p>Results</p> <p>Statistically significant decrease in WOMAC pain score were observed for Group A1 at day 90, Group A2 at 30 and 90 days and Group A3 at 60 and 90 days. Statistically significant decrease in WOMAC stiffness score were observed for Group A1 and Group A2 at 30, 60 and 90 days; but not for Group A0 and Group A3. The mean change in WOMAC functional impairment scores were statistically significant for Group A1 and Group A2 respectively at 30 days (p = 0.006 and p = 0.006), at 60 days (p = 0.016 and p = 0.002) and at 90 days (p = 0.018 and p = 0.002), these changes were not significant for Group A0 and Group A3. Based on MOS -SF-36 questionnaires, statistically significant improvements in physical function, endurance and mental health scores were observed for all active treatment groups compared to placebo. No significant changes suggestive of toxicity in routine hematologies, serum chemistries, liver enzymes or PTT were noted in any of the treatment groups.</p> <p>Conclusion</p> <p>Based on current findings UP446 is safe and efficacious alternative to established anti-inflammatory medications for alleviating OA symptoms as measured by the WOMAC Index.</p