Mechanism of H. pylori Intracellular Entry: An in vitro Study

The majority of H. pylori reside on gastric epithelial cell surfaces and in the overlying mucus, but a small fraction of H. pylori enter host epithelial and immune cells. To explore the role of the nudA invasin in host cell entry, a ΔnudA deletion derivative of strain J99 was constructed and transformants were verified by PCR and by fluorescence in situ hybridization. AGS cells were inoculated with either wild type (WT) strain J99 or its ΔnudA mutant to determine the fraction of bacteria that were bound to the cells and inside these cells using the gentamicin protection assay. We observed no significant difference between either the density of H. pylori bound to AGS cell membranes or the density of intracellular H. pylori. To further explore this finding, separate chambers of each culture were fixed in glutaraldehyde for transmission electron microscopy (TEM) and immunogold TEM. This addition to the classical gentamicin assay demonstrated that there were significantly more intracellular, and fewer membrane-bound, H. pylori in WT-infected AGS cells than in ΔnudA allele infected cells. Thus, the sum of intracellular and membrane-bound H. pylori was similar in the two groups. Since no other similar TEM study has been performed, it is at present unknown whether our observations can be reproduced by others Taken together however, our observations suggest that the classical gentamicin protection assay is not sufficiently sensitive to analyze H. pylori cell entry and that the addition of TEM to the test demonstrate that nudA plays a role in H. pylori entry into AGS cells in vitro. In addition, deletion of the invasin gene appears to limit H. pylori to the AGS cell surface, where it may be partly protected against gentamicin. In contrast, this specific environment may render H. pylori more vulnerable to host defense and therapeutic intervention, and less prone to trigger normal immune, carcinogenic, and other developmental response pathways

Clinical presentation of meningococcal disease in childhood

Although relatively rare, meningococcal disease represents a global health problem being still the leading infectious cause of death in childhood with an overall mortality around 8%. Menin- gococcal meningitis is the most commonly recognized presenta- tion, accounting for 80% to 85% of all reported cases of menin- gococcal disease (in half of these cases sepsis is also present con- comitantly). The remaining 15-20% of cases are most commonly bloodstream infections only. Meningococcal serogroups A, B, and C account for most cases of meningococcal disease throughout the world. Recently, serogroups W-135 and X (predominantly in Africa) and group Y (in the United States and European countries) have emerged as important disease-causing isolates. Despite recent advances in medical management, the mortality rate of fulminant meningococcemia ranges from 15% to 30%. However, among survivors, 10-30% could have long term sequelae (i.e. sensoneural hearing loss, seizure, motor problems, hydrocepha- lus, mental retardation, and cognitive and behavioral problems). Considering the clinical severity of meningococcal disease, pre- vention represents the first approach for avoiding serious com- plications and possible deaths. The availability of new vaccines able to cover the emerging serotypes including A and Y as well as the availability on the market of new products that could prevent meningococcal B infection represent a great opportunity for the decrease of the burden of this complicated disease. The full article is free available on www.jpmh.or

A linguistic approach to the psychosis continuum: (dis)similarities and (dis)continuities in how clinical and non-clinical voice-hearers talk about their voices

Introduction: “Continuum” approaches to psychosis have generated reports of similarities and differences in voice-hearing in clinical and non-clinical populations at the cohort level, but not typically examined overlap or degrees of difference between groups. Methods: We used a computer-aided linguistic approach to explore reports of voice-hearing by a clinical group (Early Intervention in Psychosis service-users; N = 40) and a non-clinical group (spiritualists; N = 27). We identify semantic categories of terms statistically overused by one group compared with the other, and by each group compared to a control sample of non-voice-hearing interview data (log likelihood (LL) value 6.63+=p < .01; effect size measure: log ratio 1.0+). We consider whether individual values support a continuum model. Results: Notwithstanding significant cohort-level differences, there was considerable continuity in language use. Reports of negative affect were prominent in both groups (p < .01, log ratio: 1.12+). Challenges of cognitive control were also evident in both cohorts, with references to “disengagement” accentuated in service-users (p < .01, log ratio: 1.14+). Conclusion: A corpus linguistic approach to voice-hearing provides new evidence of differences between clinical and non-clinical groups. Variability at the individual level provides substantial evidence of continuity with implications for cognitive mechanisms underlying voice-hearing

Sequential determination of calcium distribution in B cells at the various phases of glucose-induced insulin secretion

Localization and quantification of calcium pyroantimonate precipitates within the B cells, and determination of insulin secretion were performed in rat pancreas perfused with 3.3 and 16.6 mmol/l glucose. Observations were carried out during the peak, the refractory period, and at 10 and 20 min in the second phase of glucose secretion after the start of a glucose challenge. Specific calcium pyroantimonate precipitates, assessed by EGTA cross-incubation, appeared attached to plasma membrane, Golgi complex, mitochondria, cytoplasmic matrix and secretory granules. The total number of cellular calcium pyroantimonate precipitates increased with perfusion time, being significantly higher at every time-point with the higher concentration of glucose (16.6 mmol/l) than with the 3.3 mmol/l glucose concentration. Calcium pyroantimonate precipitates showed a progressive increment both in plasma membranes and mitochondria. In the cytoplasmic matrix, B granules and Golgi complex, a sharp increase in the number of precipitates was detected at the refractory period, followed by a continuous decrease until the end of the experiment. These results show that the number of calcium pyroantimonate precipitates, localized in different organelles, changes according to the functional state of B cells. They stress the importance of intracellular readily exchangeable pools as regulators of calcium availability for insulin stimulus-secretion coupling.Centro de Endocrinología Experimental y Aplicad

Towards on line monitoring the evolution of the myocardium infarction scar with an implantable electrical impedance spectrum monitoring system.

The human heart tissue has a limited capacity for regeneration. Tissue and cellular therapies based on the use of stem cells may be useful alternatives to limit the size of myocardial infarction. In this paper, the preliminary results from an experimental campaign for on-line monitoring of myocardium scar infarction are presented. This study has been carried out under a research project that has as main objective the development and application of a bioactive patch implant for regeneration of myocardial infarction. Electrical Impedance Spectroscopy (EIS) has been chosen as a tissue state monitoring technique. What is presented in this communication is the first results of an implantable EIS measurement system which has been implanted in a subset of the animals corresponding to the control group, along one month. In all the animals, the myocardial infarction was induced by the ligation of the first circumflex marginal artery. In the animal group presented,the bioactive patch scaffold and the electrodes were implanted without the stem cells load. The scaffold is a piece of decellularized human pericardium, lyophilized and rehydrated with hydrogel RAD16-I. Nanogold particles were also placed near the electrodes to improve the electrode area conductivity. The results presented correspond to the subset of animals (n = 5), which had implanted the bioimpedance system monitoring the electrical impedance spectrum in vivo during 1 month. Two electrodes were connected to the bioactive patch implant. A total of 14 logarithmically spaced frequencies were measured every 5 minutes, from 100 Hz to 200 kHz. Results show a convergence of low-frequency and high frequency impedance magnitudes along the measurement period, which is coherent with the scar formation.Postprint (published version

A structural and biochemical model of processive chitin synthesis

Chitin synthases (CHS) produce chitin, an essential component of the fungal cell wall. The molecular mechanism of processive chitin synthesis is not understood, limiting the discovery of new inhibitors of this enzyme class. We identified the bacterial glycosyltransferase NodC as an appropriate model system to study the general structure and reaction mechanism of CHS. A high throughput screening-compatible novel assay demonstrates that a known inhibitor of fungal CHS also inhibit NodC. A structural model of NodC, on the basis of the recently published BcsA cellulose synthase structure, enabled probing of the catalytic mechanism by mutagenesis, demonstrating the essential roles of the DD and QXXRW catalytic motifs. The NodC membrane topology was mapped, validating the structural model. Together, these approaches give insight into the CHS structure and mechanism and provide a platform for the discovery of inhibitors for this antifungal target

Metaphor and intertextuality in media framings of the (1984-85) British Miners' Strike:a multimodal analysis

The British Miners’ Strike of 1984-1985 represents one of the most pivotal periods in British industrial relations. Media stance toward the miners remains a controversial issue today, as attested by recent publications looking back at the strike (Williams 2009a, 2014). Here, authors including miners, journalists and other commentators argue that media coverage of the strike followed a consistently anti trade union agenda in which the media sought to destabilise the strike. An internal BBC report only recently made public shows that the BBC themselves had concerns over possible imbalances in their coverage of the so-called ‘Battle of Orgreave’ (Harcup 2014). Despite the weight attached to media coverage in this context, however, surprisingly little research has been conducted from a discourse-analytical perspective to show systematically and empirically how such an agenda may have been manifested across media texts. In this paper, drawing on Critical Cognitive Linguistics, I show how one particular metaphorical framing of the strike, which construed the strike as a war between the State and the National Union of Miners, persisted through the year long period and consider the potential ideological functions of this framing in media strategies of (de)legitimation. I show how this metaphor featured in linguistic, visual and multimodal forms of media representatio

Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

The role of metaphor in shaping the identity and agenda of the United Nations: the imagining of an international community and international threat

This article examines the representation of the United Nations in speeches delivered by its Secretary General. It focuses on the role of metaphor in constructing a common ‘imagining’ of international diplomacy and legitimising an international organisational identity. The SG legitimises the organisation, in part, through the delegitimisation of agents/actions/events constructed as threatening to the international community and to the well-being of mankind. It is a desire to combat the forces of menace or evil which are argued to motivate and determine the organisational agenda. This is predicated upon an international ideology of humanity in which difference is silenced and ‘working towards the common good’ is emphasised. This is exploited to rouse emotions and legitimise institutional power. Polarisation and antithesis are achieved through the employment of metaphors designed to enhance positive and negative evaluations. The article further points to the constitutive, persuasive and edifying power of topic and situationally-motivated metaphors in speech-making