Interleukin-1beta induces human proximal tubule cell injury, alpha-smooth muscle actin expression and fibronectin production

BACKGROUND Tubulointerstitial lesions, characterized by tubular injury, interstitial fibrosis and the appearance of myofibroblasts, are the strongest predictors of the degree and progression of chronic renal failure. These lesions are typically preceded by macrophage infiltration of the tubulointerstitium, raising the possibility that these inflammatory cells promote progressive renal disease through fibrogenic actions on resident tubulointerstitial cells. The aim of the present study, therefore, was to investigate the potentially fibrogenic mechanisms of interleukin-1beta (IL-1beta), a macrophage-derived pro-inflammatory cytokine, on human proximal tubule cells (PTC). METHODS Confluent, quiescent, passage 2 PTC were established in primary culture from histologically normal segments of human renal cortex (N = 11) and then incubated in serum- and hormone-free media supplemented with either IL-1beta (0 to 4 ng/mL) or vehicle (control). RESULTS IL-1beta significantly enhanced fibronectin secretion by up to fourfold in a time- and concentration-dependent fashion. This was accompanied by significant (2.5- to 6-fold) increases in alpha-smooth muscle actin (alpha-SMA) expression, transforming growth factor beta (TGF-beta1) secretion, nitric oxide (NO) production, NO synthase 2 (NOS2) mRNA and lactate dehydrogenase (LDH) release. Cell proliferation was dose-dependently suppressed by IL-1beta. NG-methyl-l-arginine (L-NMMA; 1 mmol/L), a specific inhibitor of NOS, blocked NO production but did not alter basal or IL-1beta-stimulated fibronectin secretion. In contrast, a pan-specific TGF-beta neutralizing antibody significantly blocked the effects of IL-1beta on PTC fibronectin secretion (IL-1beta, 268.1 +/- 30.6 vs. IL-1beta+alphaTGF-beta 157.9 +/- 14.4%, of control values, P < 0.001) and DNA synthesis (IL-1beta 81.0 +/- 6.7% vs. IL-1beta+alphaTGF-beta 93.4 +/- 2.1%, of control values, P < 0.01). CONCLUSION IL-1beta acts on human PTC to suppress cell proliferation, enhance fibronectin production and promote alpha-smooth muscle actin expression. These actions appear to be mediated by a TGF-beta1 dependent mechanism and are independent of nitric oxide release.

Fetuin-A : a major fetal serum protein that promotes "wound closure" and scarless healing [Letter to the Editor]

Burn-wound healing is a dynamic, interactive process involving a number of cellular and molecular events and is characterized by inflammation, granulation tissue formation, re-epithelialization, and tissue remodeling (Greenhalgh, 2002; Linares, 2002). Unlike incisional-wound healing, it also requires extensive re-epithelialization due to a predominant horizontal loss of tissue and often heals with abnormal scarring when burns involve deep dermis. The early mammalian fetus has the remarkable ability to regenerate normal epidermis and dermis and to heal dermal incisional wounds with no signs of scarring. Extensive research has indicated that scarless healing appears to be intrinsic to fetal skin (McCallion and Ferguson, 1996; Ferguson and O’Kane, 2004). Previously, we reported a fetal burn model, in which 80-day-old ovine fetuses (gestation¼ 145–153 days) healed deep dermal partial thickness burns without scars, whereas postnatal lambs healed equal depth burns with significant scarring (Cuttle et al., 2005; Fraser et al., 2005). This burn model provided early evidence that fetal skin has the capacity to repair and restore dermal horizontal loss, not just vertical injuries.

Manifestations of preoperational reasoning on similar programming tasks

In this research paper, we study a simple programming problem that only requires knowledge of variables and assignment statements, and yet we found that some early novice programmers had difficulty solving the problem. We also present data from think aloud studies which demonstrate the nature of those difficulties. We interpret our data within a neo-Piagetian framework which describes cognitive developmental stages through which students pass as they learn to program. We describe in detail think aloud sessions with novices who reason at the neo-Piagetian preoperational level. Those students exhibit two problems. First, they focus on very small parts of the code and lose sight of the "big picture". Second, they are prone to focus on superficial aspects of the task that are not functionally central to the solution. It is not until the transition into the concrete operational stage that decentration of focus occurs, and they have the cognitive ability to reason about abstract quantities that are conserved, and are equipped to adapt skills to closely related tasks. Our results, and the neo-Piagetian framework on which they are based, suggest that changes are necessary in teaching practice to better support novices who have not reached the concrete operational stage.

The nature and correlates of young women's peer-directed protective behavioral strategies

Objective Recently, a number of studies have identified self-employed Protective Behavioral Strategies (PBS) as effective in decreasing the level of alcohol-related harm among young people. However, much of the published research has ignored important gender differences, such as women's increased tendency to rely on PBS that are social in nature. To further the understanding of women's PBS, the current study sought to investigate the nature and correlates of the strategies young women employ to keep their friends safe when drinking (i.e., peer-directed PBS). Method A scale measuring peer-directed PBS was developed and administered in conjunction with existing measures of alcohol consumption, personal PBS, and peer attachment. Participants consisted of 422 women aged 18–30 years, recruited among psychology students and the general public. Results Exploratory factor analysis revealed two clusters of peer-directed PBS; those that were aimed at reducing intoxication among one's friends and those that were designed to minimize alcohol-related harms. Further analysis found a positive relationship between women's tendency to implement personal and peer-directed PBS and that risky drinkers were less likely to engage in personal or peer-directed PBS (either type). Conclusion Findings indicate that personal and peer-directed PBS are related behaviors that are less frequently adopted by risky drinkers.

Applying quantile regression for modeling equivalent property damage only crashes to identify accident blackspots

Hot spot identification (HSID) aims to identify potential sites—roadway segments, intersections, crosswalks, interchanges, ramps, etc.—with disproportionately high crash risk relative to similar sites. An inefficient HSID methodology might result in either identifying a safe site as high risk (false positive) or a high risk site as safe (false negative), and consequently lead to the misuse the available public funds, to poor investment decisions, and to inefficient risk management practice. Current HSID methods suffer from issues like underreporting of minor injury and property damage only (PDO) crashes, challenges of accounting for crash severity into the methodology, and selection of a proper safety performance function to model crash data that is often heavily skewed by a preponderance of zeros. Addressing these challenges, this paper proposes a combination of a PDO equivalency calculation and quantile regression technique to identify hot spots in a transportation network. In particular, issues related to underreporting and crash severity are tackled by incorporating equivalent PDO crashes, whilst the concerns related to the non-count nature of equivalent PDO crashes and the skewness of crash data are addressed by the non-parametric quantile regression technique. The proposed method identifies covariate effects on various quantiles of a population, rather than the population mean like most methods in practice, which more closely corresponds with how black spots are identified in practice. The proposed methodology is illustrated using rural road segment data from Korea and compared against the traditional EB method with negative binomial regression. Application of a quantile regression model on equivalent PDO crashes enables identification of a set of high-risk sites that reflect the true safety costs to the society, simultaneously reduces the influence of under-reported PDO and minor injury crashes, and overcomes the limitation of traditional NB model in dealing with preponderance of zeros problem or right skewed dataset.

Making arrangements in talk-in-interaction

Arrangement-making is understood to be a ‘closing-relevant action’ (Schegloff & Sacks 1973), but little attention has been given to how people arrive at mutually acceptable plans for the future. Telephone conversations between clients and staff of Community and Home Care (CHC) services were studied to identify how arrangements for future services were made. A recurrent sequence was observed in which clients were informed of future arrangement and were prompted to reply with ‘response solicitation’ (Jefferson 1981). Response solicitations were observed at two points: either tagged to the end of an informing, or following a recipient’s response to the informing. We show how response solicitations are routinely used in instances where recipients have some discretion in relation to the arrangement under discussion. They are a means by which an informing party can display to their interlocutor that they, as recipient, have some discretion to exercise in the matter. These findings are discussed with reference to prior research on arrangement-making in other settings, which suggests the general nature of this practice.

Divergent outcomes following transcytosis of IgG targeting intracellular and extracellular chlamydial antigens

Antibodies can play a protective but non-essential role in natural chlamydial infections dependent on antigen specificity and antibody isotype. IgG is the dominant antibody in both male and female reproductive tract mucosal secretions, and is bi-directionally trafficked across epithelia by the neonatal Fc receptor (FcRn). Using physiologically relevant pH-polarized epididymal epithelia grown on Transwells®, IgG specifically targeting an extracellular chlamydial antigen; the Major Outer Membrane Protein (MOMP), enhanced uptake and translocation of infection at pH 6-6.5 but not at neutral pH. This was dependent on FcRn expression. Conversely, FcRn-mediated transport of IgG targeting the intracellular chlamydial inclusion membrane protein A (IncA), induced aberrant inclusion morphology, recruited autophagic proteins independent of lysosomes, and significantly reduced infection. Challenge of female mice with MOMP-specific IgG-opsonized C. muridarum delayed infection clearance but exacerbated oviduct occlusion. In male mice, MOMP-IgG elicited by immunization afforded no protection against testicular chlamydial infection, whereas; the transcytosis of IncA-IgG significantly reduced testicular chlamydial burden. Together these data show that the protective and pathological effects of IgG are dependent on FcRn-mediated transport as well as the specificity of IgG for intracellular or extracellular antigens.

Immunity against a Chlamydia infection and disease may be determined by a balance of IL-17 signaling

Most vaccines developed against Chlamydia using animal models provide partial protection against a genital tract infection. However, protection against the oviduct pathology associated with infertility is highly variable and often has no defining immunological correlate. When comparing two adjuvants (CTA1-DD and a combination of Cholera toxin plus CpG- oligodeoxynucleotide–CT/CpG) combined with the chlamydial major outer membrane protein (MOMP) antigen and delivered via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, we identified two vaccine groups with contrasting outcomes following infection. SL immunization with MOMP/CTA1-DD induced a 70% reduction in the incidence of oviduct pathology, without significantly altering the course of infection. Conversely, IN immunization with MOMP/CT/CpG prevented an ascending infection, but not the oviduct pathology. This anomaly presented a unique opportunity to study the mechanisms by which vaccines can prevent oviduct pathology, other than by controlling the infection. The IL-17 signaling in the oviducts was found to associate with both the enhancement of immunity to infection and the development of oviduct pathology. This conflicting role of IL-17 may provide some explanation for the discordance in protection between infection and disease and suggests that controlling immunopathology, as opposed to the rapid eradication of the infection, may be essential for an effective human chlamydial vaccine that prevents infertility.

From single crystal surfaces to single atoms : investigating active sites in electrocatalysis

Electrocatalytic processes will undoubtedly be at the heart of energising future transportation and technology with the added importance of being able to create the necessary fuels required to do so in an environmentally friendly and cost effective manner. For this to be successful two almost mutually exclusive surface properties need to be reconciled, namely producing highly active/reactive surface sites that exhibit long term stability. This article reviews the various approaches which have been undertaken to study the elusive nature of these active sites on metal surfaces which are considered as adatoms or clusters of adatoms with low coordination number. This includes the pioneering studies at extended well defined stepped single crystal surfaces using cyclic voltammetry up to the highly sophisticated in situ electrochemical imaging techniques used to study chemically synthesised nanomaterials. By combining the information attained from single crystal surfaces, individual nanoparticles of defined size and shape, density functional theory calculations and new concepts such as mesoporous multimetallic thin films and single atom electrocatalysts new insights into the design and fabrication of materials with highly active but stable active sites can be achieved. The area of electrocatalysis is therefore not only a fascinating and exciting field in terms of realistic technological and economical benefits but also from the fundamental understanding that can be acquired by studying such an array of interesting materials.

University Students Depression Inventory : measurement model and psychometric properties

Depression is a serious condition that impacts the academic success and emotional well-being of the university students globally. Keeping in view the debilitating nature of this condition, the present study examined the stability of the factor structure and psychometric properties of the University Student Depression Inventory (USDI; Khawaja and Bryden, 2006). There is a need to translate and validate the scale for Persian speaking students, who live in Iran, its neighboring countries and in many other Western countries. The scale was translated into the Persian language and was used as part of a battery consisting of the scales measuring suicide, depression, stress, happiness and academic achievement. The battery was administered to 359 undergraduate students, and an additional 150 students who had been referred to the mental health center of the University of Tehran as clinical sample. Confirmatory factor analysis upheld the original three-factor structure. The results exhibited internal consistency, test-retest reliability, convergent, and divergent validity, and discriminant validity. There were gender differences and male had higher mean scores on Lethargy, Cognitive\emotion, and Academic motivation subscales than female students. Findings supported the Persian version of the USDI for cross-cultural use as a valid and reliable measure in the diagnosis of depression.

Is there an app for that? A case study of the potentials and limitations of the participator turn and networked publics for classical music audience engagement

The participatory turn, fuelled by discourses and rhetoric regarding social media, and in the aftermath of the dot.com crash of the early 2000s, enrols to some extent an idea of being able to deploy networks to achieve institutional aims. The arts and cultural sector in the UK, in the face of funding cuts, has been keen to engage with such ideas in order to demonstrate value for money; by improving the efficiency of their operations, improving their respective audience experience and ultimately increasing audience size and engagement. Drawing on a case study compiled via a collaborative research project with a UK-based symphony orchestra (UKSO) we interrogate the potentials of social media engagement for audience development work through participatory media and networked publics. We argue that the literature related to mobile phones and applications (‘apps’) has focused primarily on marketing for engagement where institutional contexts are concerned. In contrast, our analysis elucidates the broader potentials and limitations of social-media-enabled apps for audience development and engagement beyond a marketing paradigm. In the case of UKSO, it appears that the technologically deterministic discourses often associated with institutional enrolment of participatory media and networked publics may not necessarily apply due to classical music culture. More generally, this work raises the contradictory nature of networked publics and argues for increased critical engagement with the concept.

Circles in the surf : Australian masculinity, mortality and grief

This article examines the constructs of masculinity that are predominant in contemporary Australian society and their influence upon men's perception of their health and well-being. It questions the currency of ‘male stoicism’ at a time when changed perceptions of masculinity are emerging. In particular, it considers how these constructs are evidenced in men's embracing of human mortality and their public expressions of grief. The nature of men's health promotion is discussed and a platform for promoting healthy approaches to masculinity, mortality and grief is presented.

Public sector project delay : the Malaysian perspective and the way forward

Construction delay has been a protracted problem for the Malaysian construction industry. Recent report showed that 80% of public sector projects are behind schedule. This underachieving time performance has led to many problems including public complaints, loss of reputation and revenue for the government and a slump in the industry’s GDP contribution. Research in the area of project delay has mushroomed worldwide with attempts to place mitigation plans, but delay remains a global phenomenon. There is now an urgent need for revolutionizing construction practices and past research, backed up with few successful cases suggests that Supply Chain Management (SCM) could prove beneficial to reduce or eliminate delays in construction. SCM which originated from the automotive manufacturing industry promotes a more collaborative approach to construction management and has recently gained attention of the construction industry. However every country, including Malaysia, would certainly have disparities of their own compared to others being it from the cultural point of view, nature of problems, locality or improvements needed. Therefore, this paper will present part of a Ph.D. research which aims at illustrating the Malaysian construction industry experts’ perception of the Malaysian public sector project delay, provide insight into these dilemmas, highlights the problems with current practices, its effects and the improvements needed. Subsequently, this paper would propose ratification to the problems using SCM. A semi-structured interview has been conducted to practitioners with at least 20 years’ experience in the industry. The findings showed that Malaysia may be unique compared to other countries and that by considering a number of additional factors, SCM could prove beneficial to increase efficiency of the Malaysian public sector projects.

Understanding the abnormal brain activity in epilepsy as a potential predictor of the onset of an epileptic seizure

The Brain Research Institute (BRI) uses various types of indirect measurements, including EEG and fMRI, to understand and assess brain activity and function. As well as the recovery of generic information about brain function, research also focuses on the utilisation of such data and understanding to study the initiation, dynamics, spread and suppression of epileptic seizures. To assist with the future focussing of this aspect of their research, the BRI asked the MISG 2010 participants to examine how the available EEG and fMRI data and current knowledge about epilepsy should be analysed and interpreted to yield an enhanced understanding about brain activity occurring before, at commencement of, during, and after a seizure. Though the deliberations of the study group were wide ranging in terms of the related matters considered and discussed, considerable progress was made with the following three aspects. (1) The science behind brain activity investigations depends crucially on the quality of the analysis and interpretation of, as well as the recovery of information from, EEG and fMRI measurements. A number of specific methodologies were discussed and formalised, including independent component analysis, principal component analysis, profile monitoring and change point analysis (hidden Markov modelling, time series analysis, discontinuity identification). (2) Even though EEG measurements accurately and very sensitively record the onset of an epileptic event or seizure, they are, from the perspective of understanding the internal initiation and localisation, of limited utility. They only record neuronal activity in the cortical (surface layer) neurons of the brain, which is a direct reflection of the type of electrical activity they have been designed to record. 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Exploring a biomimicry based approach and key barriers to evolving water infrastructure systems

Access to clean water is essential for human life and a critical issue facing much of modern society, especially as a result of the 21st Century triad of challenges – population growth, resource scarcity and pollution – which contribute to the rising complexity of providing adequate access to this essential resource for large parts of society. As such, there is now an increasing need for innovative solutions to source, treat and distribute water to cities across the globe. This position paper explores biomimicry – emulating natural form, function, process and systems – as an alternative and sustainable design approach to traditional water infrastructure systems. The key barriers to innovations such as biomimicry are summarised, indicating that regulatory and economic grounds are some of the major hindrances to integrating alternative design approaches in the water sector in developed countries. This paper examines some of the benefits of moving past these barriers to develop sustainable, efficient and resilient solutions that provide adequate access to water in the face of contemporary challenges.