Immunohistochemical comparison of CD5, lambda, and kappa expression in primary and recurrent buccal Mucosa-associated lymphoid tissue (MALT) lymphomas

Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal marginal zone B-cell lymphoma and is a distinct subtype of non-Hodgkin's lymphoma

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Differential attraction and repulsion of Staphylococcus aureus and Pseudomonas aeruginosa on molecularly smooth titanium films

Magnetron sputtering techniques were used to prepare molecularly smooth titanium thin films possessing an average roughness between 0.18 nm and 0.52 nm over 5 μm × 5 μm AFM scanning areas. Films with an average roughness of 0.52 nm or lower were found to restrict the extent of P. aeruginosa cell attachment, with less than 0.5% of all available cells being retained on the surface. The attachment of S. aureus cells was also limited on films with an average surface roughness of 0.52 nm, however they exhibited a remarkable propensity for attachment on the nano-smoother 0.18 nm average surface roughness films, with the attachment density being almost twice as great as that observed on the nano-rougher film. The difference in attachment behaviour can be attributed to the difference in morphology of the rod-shaped P. aeruginosa compared to the spherical S. aureus cells

Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases

We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment

Prospective Study of Infection, Colonization and Carriage of Methicillin-Resistant Staphylococcus Aureus in an Outbreak Affecting 990 Patients

In the three years between November 1989 and October 1992, an outbreak of methicillin-resistantStaphylococcus aureus (MRSA) affected 990 patients at a university hospital. The distribution of patients with carriage, colonization or infection was investigated prospectively. Nosocomial acquisition was confirmed in at least 928 patients, 525 of whom were identified from clinical specimens as being infected (n=418) or colonized (n=107) by MRSA. An additional 403 patients were identified from screening specimens, of whom 58 subsequently became infected and 18 colonized. Screening of the nose, throat and perineum detected 98 % of all carriers. Of the 580 infections in 476 patients, surgical wound, urinary tract and skin infections accounted for 58 % of the infections. Of the 476 infected patients, death was attributable to MRSA infection in 13 %. Colonization with MRSA was found in 127 patients and 42 % of 165 colonized sites were the skin. Auto-infection from nasal carriage or cross-infection, probably via staff hands, seemed to be the most common mode of acquisition of MRSA infections

Discovering Argumentative Patterns in Energy Polylogues: A Macroscope for Argument Mining

A macroscope is proposed and tested here for the discovery of the unique argumentative footprint that characterizes how a collective (e.g., group, online community) manages differences and pursues disagreement through argument in a polylogue. The macroscope addresses broader analytic problems posed by various conceptualizations of large-scale argument, such as fields, spheres, communities, and institutions. The design incorporates a two-tier methodology for detecting argument patterns of the arguments performed in arguing by an interactive collective that produces views, or topographies, of the ways that issues are generated in the making and defending of standpoints. The design premises for the macroscope build on insights about argument patterns from pragma-dialectical theory by incorporating research and theory on disagreement management and the Argumentum Model of Topics. The design reconceptualizes prototypical and stereotypical argument patterns for characterizing large-scale argumentation. A prototype of the macroscope is tested on data drawn from six threads about oil-drilling and fracking from the subreddit Changemyview. The implementation suggests the efficacy of the macroscope’s design and potential for identifying what communities make controversial and how the disagreement space in a polylogue is managed through stereotypical argument patterns in terms of claims/premises, inferential relations, and presentational devices

Women's gambling behaviour, product preferences, and perceptions of product harm: Differences by age and gambling risk status

Background: Women's participation in, and harm from gambling, is steadily increasing. There has been very limited research to investigate how gambling behaviour, product preferences, and perceptions of gambling harm may vary across subgroups of women. Methods: This study surveyed a convenience sample of 509 women from Victoria and New South Wales, Australia. Women were asked a range of questions about their socio-demographic characteristics and gambling behaviour. Focusing on four gambling products in Australia-casino gambling, electronic gambling machines (EGMs), horse betting, and sports betting-women were asked about their frequency of participation, their product preferences, and perceptions of product harms. The sample was segmented a priori according to age and gambling risk status, and differences between groups were identified using Chi-square tests and ANOVAs. Thematic analysis was used to interpret qualitative data. Results: Almost two thirds (n=324, 63.7%) of women had engaged with one of the four products in the previous 12 months. Compared to other age groups, younger women aged 16-34 years exhibited a higher proportion of problem gambling, gambled more frequently, and across more products. While EGMs were the product gambled on most frequently by women overall, younger women were significantly more likely to bet on sports and gamble at casinos relative to older women. Qualitative data indicated that younger women engaged with gambling products as part of a 'night out', 'with friends', due to their 'ease of access' and perceived 'chance of winning big'. There were significant differences in the perceptions of the harms associated with horse and sports betting according to age and gambling risk status, with younger women and gamblers perceiving these products as less harmful. Conclusions: This study highlights that there are clear differences in the gambling behaviour, product preferences, and perceptions of product harms between subgroups of women. A gendered approach will enable public health researchers and policymakers to ensure that the unique factors associated with women's gambling are taken into consideration in a comprehensive public health approach to reducing and preventing gambling harm

CPP-ZFN: A potential DNA-targeting anti-malarial drug

<p>Abstract</p> <p>Background</p> <p>Multidrug-resistant <it>Plasmodium </it>is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death.</p> <p>Presentation of the hypothesis</p> <p>Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells.</p> <p>Testing the hypothesis</p> <p>Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the <it>Plasmodium </it>genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between <it>Plasmodium </it>and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to <it>Plasmodium</it>-infected RBCs (iRBCs) and different <it>Plasmodium </it>organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more <it>Plasmodium </it>cell membrane translocation peptide seems achievable.</p> <p>Implications of the hypothesis</p> <p>Targeting of the <it>Plasmodium </it>genome using ZFN has great potential for the development of anti-malarial drugs. It allows the development of a single drug against all malarial infections, including multidrug-resistant strains. Availability of multiple ZFN target sites in a single gene will provide alternative drug target sites to combat the development of resistance in the future.</p

Evidence of Key Tinnitus-Related Brain Regions Documented by a Unique Combination of Manganese-Enhanced MRI and Acoustic Startle Reflex Testing

Animal models continue to improve our understanding of tinnitus pathogenesis and aid in development of new treatments. However, there are no diagnostic biomarkers for tinnitus-related pathophysiology for use in awake, freely moving animals. To address this disparity, two complementary methods were combined to examine reliable tinnitus models (rats repeatedly administered salicylate or exposed to a single noise event): inhibition of acoustic startle and manganese-enhanced MRI. Salicylate-induced tinnitus resulted in wide spread supernormal manganese uptake compared to noise-induced tinnitus. Neither model demonstrated significant differences in the auditory cortex. Only in the dorsal cortex of the inferior colliculus (DCIC) did both models exhibit supernormal uptake. Therefore, abnormal membrane depolarization in the DCIC appears to be important in tinnitus-mediated activity. Our results provide the foundation for future studies correlating the severity and longevity of tinnitus with hearing loss and neuronal activity in specific brain regions and tools for evaluating treatment efficacy across paradigms