bluuebunny/crossref_metadata_2025 huggingface dataset:
Can a focused staff training programme improve the ward atmosphere and patient satisfaction in a forensic psychiatric hospital? A pilot study
Authors: Nesset Merete Berg , Rossberg Jan Ivar , Almvik Roger , Friis Svein
Published: December 2008

Objective:  The main aim of the study was to describe whether staff training and lectures on milieu therapy to nursing staff can change the treatment environment, as perceived by the patients, in a desirable direction. The study was approved by the Regional Ethics Committee for Medical Research.

Method:  To measure the patients’ perceptions of the treatment environment we used the Ward Atmosphere Scale (WAS). The ward atmosphere was evaluated three times during a 12‐month period. Additionally, the patients completed five questions concerning satisfaction with the treatment environment. Between the first and the second ward evaluation the nursing staff was given 3 weeks of lectures on different aspects of milieu therapy. The nursing staff completed the WAS and three satisfaction items.

Results:  The study revealed a change in desired direction after education in five of the six key subscales of the WAS (Involvement, Support, Practical orientation, Angry and aggressive behaviour and Order and organization). Staff control was the only subscale with no changes. The patients also reported an increase in satisfaction. The study revealed no major changes in the staff scores. The present study included only a small number of patients and examined the changes in only one psychiatric department; hence it could be argued that the results cannot be generalized to equivalent populations within the forensic services.

Conclusions:  The study indicated that it is possible to improve the ward atmosphere in a desirable direction by a 3‐week training programme for nursing staff about important aspects of milieu therapy.
The psychometric study of the Serbian KINDL questionnaire for health‐related quality of life assessment in children and adolescents
Authors: Stevanovic Dejan , Lakic Aneta , Vilotic Jelisaveta
Published: December 2008

Objectives:  Health‐related quality of life (HRQOL) is the most frequently evaluated patient‐reported outcome. It is unexplored in Serbia and there are no methods for its evaluation. This study was aimed to analyse the psychometric properties of the Serbian version of the KINDL questionnaire for HRQOL assessment in children and adolescents.

Methods:  The KINDL‐Kid‐S completed 100 children and the KINDL‐Kiddo‐S 92 adolescents. Both versions were descriptively analysed and explored the items–sub‐scales relationships. Cronbach’s coefficient was used to explore the reliability of the versions.

Results:  The means of all sub‐scales were located on the positive side of the response scale. The total score was 78.84 for the KINDL‐Kid‐S and 75.51 for the KINDL‐Kiddo‐S. Within the versions, the items showed significant correlations with its sub‐scale total score and the total score. Between the sub‐scales, there were significant relationships also. The Cronbach’s coefficient exceeded 0.8 for the internal consistency reliability of the total score in both, and ranged 0.45–0.7 for the sub‐scales.

Conclusions:  Besides substantial inter‐ and intra‐sub‐scale correlations, the reliability coefficients of some sub‐scales are low in the Serbian KINDL, emerging the needs for revisions before extensive uses.
Alteration textures in terrestrial volcanic glass and the associated bacterial community
Authors: COCKELL C. S. , OLSSON‐FRANCIS K. , HERRERA A. , MEUNIER A.
Published: December 2008

Alteration textures were examined in subglacial (hyaloclastite) deposits at Valafell, Southern Iceland. Pitted and ‘elongate’ alteration features are observed in the glass similar to granular and tubular features reported previously in deep‐ocean basaltic glasses, but elongate features generally did not have a length to width ratio greater than five. Elongate features were found in only 7% of surfaces. Crystalline basalt clasts, which are incorporated into the hyaloclastite, did not display elongate structures. Pitted alteration features were poorly defined in crystalline basalt, comprising only 4% of the surface compared to 47% in the case of basaltic glass. Examination of silica‐rich glass (obsidian) and rhyolite similarly showed poorly defined pitted textures that comprised less than 15% of the surface and no elongate features were observed. These data highlight the differences in alteration textures between terrestrial basaltic glass and previously studied deep‐ocean and subsurface basaltic glass, and the important role of mineralogy in controlling the type and abundance of alteration features. The hyaloclastite contains a diverse and abundant bacterial population, as determined by 16S rDNA analysis, which could be involved in weathering the glass. Despite the presence of phototrophs, we show that they were not involved in the production of most alteration textures in the basaltic glass materials we examined.
Phototrophic Fe(II) oxidation in an atmosphere of H2: implications for Archean banded iron formations
Authors: CROAL L. R. , JIAO Y. , KAPPLER A. , NEWMAN D. K
Published: December 2008

The effect of hydrogen on the rate of phototrophic Fe(II) oxidation by two species of purple bacteria was measured at two different bicarbonate concentrations. Hydrogen slowed Fe(II) oxidation to varying degrees depending on the bicarbonate concentration, but even the slowest rate of Fe(II) oxidation remained on the same order of magnitude as that estimated to have been necessary to deposit the Hamersley banded iron formations. Given the hydrogen and bicarbonate concentrations inferred for the Archean, our data suggest that Fe(II) phototrophy could have been a viable process at this time.
Community cooperation with natural flood management: a case study in the Scottish Borders
Authors: Howgate Olivia Ruth , Kenyon Wendy
Published: December 2008

The cooperation of communities and landowners in the upper catchment is vital for the successful implementation of natural flood management (NFM) projects as few incentives are in place to reward them to host such projects. The aim of this paper is to initiate an exploration of the issues that affect a community's decision to cooperate. The results of a case study in Scotland show that willingness to cooperate is affected by concern about alternative flood management techniques, a sense of responsibility to help connected communities at risk of flooding and the expectation of beneficial impacts from the project. Indeed, these issues appeared to over‐ride the hostility generated towards the project as a result of poor communication and engagement with the community from organisations associated with the proposed project. The results of the research suggest that if NFM projects are to proliferate, close attention must be paid to community attitudes towards flood management and related communities at risk, and that NFM projects must be developed and implemented according to well‐established principles of public participation.
Household income diversification and the production of local meat: the prospect of small‐scale pig farming in Southern Yunnan, China
Authors: Neo Harvey , Chen Li‐Hui
Published: December 2008

This paper assesses the viability of small scale, specialised livestock farming led by the local government, to alleviate rural household poverty. In so doing, it reflects upon the prospect of niche livestock farming in an age where, ironically, demand for meat is ever‐rising. It also highlights the ambiguous role that local government plays in poverty alleviation. The specific case study is on the Jinuo ethnic minority in Xishuangbanna autonomous region, located in Southwestern province of Yunnan, China. It is argued that thus far the Jinuo minority have had modest success in rearing indigenous pigs due to a confluence of factors. Nonetheless, a growing market will likely result in some degree of intensification in the production process that goes beyond the means of the upland farmers but will be eagerly exploited by the local government. If the pig rearing scheme is to remain an effective income diversification strategy in select marginalised mountainous communities, the march towards commodification, expansion and intensification, as well as the unchecked ambition of the local government, have to be carefully moderated.
Video as an Effective Method to Deliver Pretest Information for Rapid Human Immunodeficiency Testing
Authors: Merchant Roland C. , Clark Melissa A. , Mayer Kenneth H. , Seage III George R. , DeGruttola Victor G. , Becker Bruce M.
Published: December 2008

Objectives:  Video‐based delivery of human immunodeficiency virus (HIV) pretest information might assist in streamlining HIV screening and testing efforts in the emergency department (ED). The objectives of this study were to determine if the video “Do you know about rapid HIV testing?” is an acceptable alternative to an in‐person information session on rapid HIV pretest information, in regard to comprehension of rapid HIV pretest fundamentals, and to identify patients who might have difficulties in comprehending pretest information.

Methods:  This was a noninferiority trial of 574 participants in an ED opt‐in rapid HIV screening program who were randomly assigned to receive identical pretest information from either an animated and live‐action 9.5‐minute video or an in‐person information session. Pretest information comprehension was assessed using a questionnaire. The video would be accepted as not inferior to the in‐person information session if the 95% confidence interval (CI) of the difference (Δ) in mean scores on the questionnaire between the two information groups was less than a 10% decrease in the in‐person information session arm’s mean score. Linear regression models were constructed to identify patients with lower mean scores based upon study arm assignment, demographic characteristics, and history of prior HIV testing.

Results:  The questionnaire mean scores were 20.1 (95% CI = 19.7 to 20.5) for the video arm and 20.8 (95% CI = 20.4 to 21.2) for the in‐person information session arm. The difference in mean scores compared to the mean score for the in‐person information session met the noninferiority criterion for this investigation (Δ = 0.68; 95% CI = 0.18 to 1.26). In a multivariable linear regression model, Blacks/African Americans, Hispanics, and those with Medicare and Medicaid insurance exhibited slightly lower mean scores, regardless of the pretest information delivery format. There was a strong relationship between fewer years of formal education and lower mean scores on the questionnaire. Age, gender, type of insurance, partner/marital status, and history of prior HIV testing were not predictive of scores on the questionnaire.

Conclusions:  In terms of patient comprehension of rapid HIV pretest information fundamentals, the video was an acceptable substitute to pretest information delivered by an HIV test counselor. Both the video and the in‐person information session were less effective in providing pretest information for patients with fewer years of formal education.
Where to Focus Efforts to Improve Overall Ratings of Care and Willingness to Return: The Case of Tuscan Emergency Departments
Authors: Seghieri Chiara , Sandoval Guillermo A. , Brown Adalsteinn D. , Nuti Sabina
Published: December 2008

Objectives:  Both regression and optimization models were used to identify an efficient combination of aspects of care (e.g., comfort of waiting room) necessary to improve global emergency department (ED) patient satisfaction. The approach, based on patient survey data, tends to favor aspects of care with large regression coefficients and those whose current performance is low, because improvements produce a greater effect on global satisfaction.

Methods:  The authors used ED patient satisfaction survey data collected between September and October 2007 from a random sample of 5,277 adult patients who visited 43 EDs in Tuscany, Italy. Ordinal logistic regression models were run to predict overall ratings of care and willingness to return using 20 independent variables (i.e., aspects of care). An optimization model was run to increase these two global items to a maximum of 15%. This model minimizes the total combined percentage increase of the aspects of care. Models using all cases (n = 5,277), cases from local hospitals (n = 4,264), and cases from teaching hospitals (n = 1,013) were run.

Results:  Four aspects selected by the optimization algorithm were in all models: “satisfaction with waiting time,”“comfort of the waiting room,”“professionalism of physicians” (technical skills), and “level of collaboration between physicians and nursing staff.” Most aspects needed a 15% increase to comply with the percentage increases set for the global satisfaction items. The model found that to increase overall ratings of care by 1, 2, or 8%, hospitals would need to focus only on one aspect: “level of collaboration between physicians and nursing staff.” The total number of variables increased to six when the improvement in overall ratings of care was set at 15%. To increase 3 or 5% willingness to return, the optimization algorithm found that 6 or 14 aspects, respectively, are needed. An increase of 6% or more was unfeasible.

Conclusions:  This approach is only somewhat efficient, as a cost structure is absent. The optimization model assumes that the cost to increase each aspect by 1% is equivalent. By applying this modeling technique we have demonstrated that, at least, two elements are important to consider when developing efficient improvement strategies to increase global satisfaction: 1) the current level of satisfaction of the aspects of care and 2) the importance ascribed to the aspects of care. A third element, the cost to increase the aspects of care, might also be important. However, the impact of this element on the optimal solution is currently unknown.
Identification of the first in cis mutations in MYH9 disorder
Authors: Miyajima Yuji , Kunishima Shinji
Published: December 2008

Here, we report the first in cis mutations in exon 1 of the MYH9 gene in a patient with MYH9 disorder. The patient was a 5‐yr‐old girl with macrothrombocytopenia and conspicuous cytoplasmic inclusion bodies in neutrophils. Immunofluorescence analysis of neutrophil non‐muscle myosin heavy chain‐II A (NMMHC‐IIA) indicated several cytoplasmic spots of NMMHC‐IIA aggregates that were circular to oval in shape (type II pattern). Mutational analysis showed two mutations, c.99G > T and c.103C > G, which would result in p.W33C and p.P35A, respectively, in exon 1 of the MYH9 gene. In addition, concurrent mutations were present on the same chromosome. Inclusion bodies are usually faint or mostly invisible in MYH9 disorders with a mutation in exon 1. In this case, double mutations might have caused the large myosin protein aggregation and accumulation. Although not observed in this patient, the development of Alport manifestations should be monitored by careful follow‐up.
Increased expression of TRPV1 channel in intrinsically aged and photoaged human skin in vivo
Authors: Lee Young Mee , Kim Yeon Kyung , Chung Jin Ho
Published: December 2008

Abstract:  Transient receptor potential vanilloid type 1 (TRPV1) is activated by various stimuli including capsaicin, heat and acid. While TRPV1 has been localized in the epidermis, little is known about the physiological role of TRPV1 in the skin, especially in skin ageing. In this study, we investigated the effect of acute UV irradiation on TRPV1 expression in human skin and the changes in TRPV1 mRNA and protein in intrinsic ageing and photoageing using human sun‐protected (upper inner arm) and sun‐exposed (forearm) skin of young and elderly subjects.

Western blot analysis of UV‐irradiated young buttock skin revealed that the expression of TRPV1 protein was increased at 24 h (2.3‐fold) and 48 h (2.4‐fold) after UV irradiation. Real‐time PCR analysis also showed that the mRNA level of TRPV1 was augmented by 2.4‐fold at 4 h after UV irradiation. TRPV1 protein was expressed at higher levels by 2.6‐fold in the sun‐protected skin of the elderly subjects than in that of young people according to western blotting, real‐time PCR analysis and immunohistochemical staining. In addition, the photoaged skin of elderly showed increased expression of TRPV1 mRNA and protein compared with that of the sun‐protected skin of the same individuals. Also, we found increased expression of TRPV1 in nerve fibres of elderly persons using double staining of TRPV1 and nerve fibres.

Based on the above results, our data suggest that the expression of TRPV1 is affected by both the intrinsic ageing and photoageing processes.
Candida albicans phospholipomannan triggers inflammatory responses of human keratinocytes through Toll‐like receptor 2
Authors: Li Min , Chen Qing , Shen Yongnian , Liu Weida
Published: December 2008

Abstract:  The Toll‐like receptors (TLRs) play an important role in the recognition of Candida albicans components and activation of innate immunity. Phospholipomannan (PLM), a glycolipid, is expressed at the surface of C. albicans cell wall, which acts as a member of the pathogen‐associated molecular patterns family. In this study, we sought to clarify whether C. albicans‐native PLM could induce an inflammation response in human keratinocytes and to determine the underlying mechanisms. Exposure of cultured human primary keratinocytes to PLM led to the increased gene expression and secretion of proinflammatory cytokines (IL‐6) and chemokines (IL‐8). PLM hydrolysed with β‐d‐mannoside mannohydrolase failed to induce gene expression and secretion of IL‐6 and IL‐8. PLM up‐regulated the mRNA and protein levels of TLR2, whereas the mRNA level of TLR4 was not altered. Keratinocytes challenged with PLM resulted in the activation of NF‐κB and mitogen‐activated protein kinase (MAPKs) including p38. Anti‐TLR2 neutralizing antibody, NFκB and p38MAPK inhibitors blocked the PLM‐induced secretion of IL‐6, IL‐8 in keratinocytes, but no such effect was observed in pretreatment with anti‐TLR4‐neutralizing antibody and lipopolysaccharide inhibitor (polymyxin B). These data suggest C. albicans‐native PLM may contribute to the inflammatory responses of cutaneous candidiasis in the TLR2‐NF‐κB and p38MAPK signalling pathway dependent manner.
Inflammatory signals in dendritic cell activation and the induction of adaptive immunity
Authors: Joffre Olivier , Nolte Martijn A. , Spörri Roman , Sousa Caetano Reis e
Published: December 2008

Summary:  Pathogen invasion induces a rapid inflammatory response initiated through the recognition of pathogen‐derived molecules by pattern recognition receptors (PRRs) expressed on both immune and non‐immune cells. The initial wave of pro‐inflammatory cytokines and chemokines limits pathogen spread and recruits and activates immune cells to eradicate the invaders. Dendritic cells (DCs) are responsible for initiating a subsequent phase of immunity, dominated by the action of pathogen‐specific T and B cells. As for the early pro‐inflammatory response, DC activation is triggered by PRR signals. These signals convert resting DCs into potent antigen‐presenting cells capable of promoting the expansion and effector differentiation of naive pathogen‐specific T cells. However, it has been argued that signals from PRRs are not a prerequisite for DC activation and that pro‐inflammatory cytokines have the same effect. Although this may appear like an efficient way to expand the number of DCs that initiate adaptive immunity, evidence is accumulating that DCs activated indirectly by inflammatory cytokines are unable to induce functional T‐cell responses. Here, we review the differences between PRR‐triggered and cytokine‐induced DC activation and speculate on a potential role for DCs activated by inflammatory signals in tolerance induction rather than immunity.
The long pentraxin PTX3 as a prototypic humoral pattern recognition receptor: interplay with cellular innate immunity
Authors: Bottazzi Barbara , Garlanda Cecilia , Cotena Alessia , Moalli Federica , Jaillon Sebastien , Deban Livija , Mantovani Alberto
Published: December 2008

Summary:  The innate immune system consists of a cellular arm and a humoral arm. Components of humoral immunity include diverse molecular families, which represent functional ancestors of antibodies. They play a key role as effectors and modulators of innate resistance in animals and humans, interacting with cellular innate immunity. The prototypic long pentraxin, pentraxin 3 (PTX3), represents a case in point of this interplay. Gene targeting of this evolutionarily conserved long pentraxin has unequivocally defined its role at the crossroads of innate immunity, inflammation, matrix deposition, and female fertility. Phagocytes represent a key source of this fluid‐phase pattern recognition receptor, which, in turn, facilitates microbial recognition by phagocytes acting as an opsonin. Moreover, PTX3 has modulatory functions on innate immunity and inflammation. Here, we review the studies on PTX3 which emphasize the complexity and complementarity of the crosstalk between the cellular and humoral arms of innate immunity.
DAP10‐ and DAP12‐associated receptors in innate immunity
Authors: Lanier Lewis L.
Published: December 2008

Summary:  The DAP10 and DAP12 signaling subunits are highly conserved in evolution and associate with a large family of receptors in hematopoietic cells, including dendritic cells, plasmacytoid dendritic cells, neutrophils, basophils, eosinophils, mast cells, monocytes, macrophages, natural killer cells, and some B and T cells. Some receptors are able to associate with either DAP10 or DAP12, which contribute unique intracellular signaling functions. Studies of humans and mice deficient in these signaling subunits have provided surprising insights into the physiological functions of DAP10 and DAP12, demonstrating that they can either activate or inhibit immune responses. DAP10‐ and DAP12‐associated receptors have been shown to recognize both host‐encoded ligands and ligands encoded by microbial pathogens, indicating that they play an important role in innate immune responses.
RNA‐based viral immunity initiated by the Dicer family of host immune receptors
Authors: Aliyari Roghiyh , Ding Shou‐Wei
Published: December 2008

Summary:  Suppression of viral infection by RNA in a nucleotide sequence homology‐dependent manner was first reported in plants in early 1990s. Studies in the past 15 years have established a completely new RNA‐based immune system against viruses that is mechanistically related to RNA silencing or RNA interference (RNAi). This viral immunity begins with recognition of viral double‐stranded or structured RNA by the Dicer nuclease family of host immune receptors. In fungi, plants and invertebrates, the viral RNA trigger is processed into small interfering RNAs (siRNAs) to direct specific silencing of the homologous viral genomic and/or messenger RNAs by an RNaseH‐like Argonaute protein. Deep sequencing of virus‐derived siRNAs indicates that the immunity against viruses with a positive‐strand RNA genome is induced by Dicer recognition of dsRNA formed during the initiation of viral progeny (+)RNA synthesis. The RNA‐based immune pathway in these organisms overlaps the canonical dsRNA‐siRNA pathway of RNAi and may require amplification of viral siRNAs by host RNA‐dependent RNA polymerase in plants and nematodes. Production of virus‐derived small RNAs is undetectable in mammalian cells infected with RNA viruses. However, infection of mammals with several nucleus‐replicating DNA viruses induces production of virus‐derived microRNAs capable of silencing host and viral mRNAs as found for viral siRNAs. Remarkably, recent studies indicate that prokaryotes also produce virus‐derived small RNAs known as CRISPR RNAs to guide antiviral defense in a manner that has yet to be defined. In this article, we review the recent progress on the identification and mechanism of the key components including viral sensors, viral triggers, effectors, and amplifiers, of the small RNA‐directed viral immunity. We also highlight some of the many unresolved questions.
Approaching the RNA ligand for RIG‐I?
Authors: Schlee Martin , Hartmann Evelyn , Coch Christoph , Wimmenauer Vera , Janke Markus , Barchet Winfried , Hartmann Gunther
Published: December 2008

Summary:  Innate and antigen‐specific antiviral immunity are triggered by immunorecognition of viral nucleic acids. The helicase retinoic acid‐inducible gene I (RIG‐I) (also known as DDX58) is the key sensor of negative strand RNA viruses in the cytosol of cells. RNA containing a triphosphate at the 5′‐end was shown to activate RIG‐I, but the exact structure of RNA supporting 5′‐triphosphate recognition, the requirement of a 5′‐triphosphate group, as well as the existence of RNA structures detected by RIG‐I in the absence of 5′‐triphosphate remain controversial. Here, we revisit the literature on RIG‐I and RIG‐I ligands. The literature proposes at least six different RIG‐I ligands: (i) single strand with a 5′‐triphosphate, (ii) double‐stranded RNA with a 5′‐triphosphate, (iii) 5′‐triphosphate single‐stranded RNA with A‐ and U‐rich 3′‐sequences, (iv) double‐stranded RNA of intermediate length (>300 and <2000 bp) without 5′‐triphosphate, (v) blunt‐end short double‐stranded RNA (23–30 bp) without 5′‐triphosphate, and (vi) short double‐stranded RNA (23–30 bp) with 5′‐monophosphate. RIG‐I thus seems promiscuous for a variety of different RNA molecules, very similar to the Toll‐like receptors, of which 10 family members are sufficient for the safe detection of the microbial cosmos. In the light of these outstanding publications, it seems an unlikely possibility that there is a fundamental shortcoming in the design of all studies. Looking closely, the only issue that comes to mind is the in vitro transcription technique used by all investigators without confirming the identity of RNA products. This technique, together with the different biological systems used, the lack of dose responses and of proper comparison of different published ligands and controls leave us with more questions than answers as to what the exact RIG‐I ligand is, if in fact it exists.
Autophagy and pattern recognition receptors in innate immunity
Authors: Delgado Monica , Singh Sudha , De Haro Sergio , Master Sharon , Ponpuak Marisa , Dinkins Christina , Ornatowski Wojciech , Vergne Isabelle , Deretic Vojo
Published: December 2008

Summary:  Autophagy is a physiologically and immunologically controlled intracellular homeostatic pathway that sequesters and degrades cytoplasmic targets including macromolecular aggregates, cellular organelles such as mitochondria, and whole microbes or their products. Recent advances show that autophagy plays a role in innate immunity in several ways: (i) direct elimination of intracellular microbes by digestion in autolysosomes, (ii) delivery of cytosolic microbial products to pattern recognition receptors (PRRs) in a process referred to as topological inversion, and (iii) as an anti‐microbial effector of Toll‐like receptors and other PRR signaling. Autophagy eliminates pathogens in vitro and in vivo but, when aberrant due to mutations, contributes to human inflammatory disorders such as Crohn’s disease. In this review, we examine these relationships and propose that autophagy is one of the most ancient innate immune defenses that has possibly evolved at the time of α‐protobacteria–pre‐eukaryote relationships, leading up to modern eukaryotic cell–mitochondrial symbiosis, and that during the metazoan evolution, additional layers of immunological regulation have been superimposed and integrated with this primordial innate immunity mechanism.
Viral sensors: diversity in pathogen recognition
Authors: McCartney Stephen A. , Colonna Marco
Published: December 2008

Summary:  Innate sensors of viral infection detect viral products and initiate the signal cascades that lead to the antiviral response. Several proteins have been identified to play a role in this process, mostly members of the Toll‐like receptor and retinoic acid‐inducible gene I‐like receptor families. These receptors have been demonstrated to function in part by recognizing a diverse yet unique repertoire of nucleic acid substrates. Upon recognition of their ligands, these sensors activate distinct signaling pathways that lead to the secretion of type I interferon and inflammatory cytokines. It remains to be seen, however, if these sensors are redundant or whether each serves a unique function. In this work, we review the current knowledge of viral sensors, speculate on how they may function in vivo, and explore the potential reasons for their diversity.
RNA recognition and signal transduction by RIG‐I‐like receptors
Authors: Yoneyama Mitsutoshi , Fujita Takashi
Published: December 2008

Summary:  Viral infection is detected by cellular sensor molecules as foreign nucleic acids and initiates innate antiviral responses, including the activation of proinflammatory cytokines and type I interferon (IFN). Recent identification of cytoplasmic viral sensors, such as retinoic acid‐inducible gene‐I‐like receptors (RLRs), highlights their significance in the induction of antiviral innate immunity. Moreover, it is intriguing to understand how they can discriminate endogenous RNA from foreign viral RNA and initiate signaling cascades leading to the induction of type I IFNs. This review focuses on the current understanding of the molecular machinery underlying RNA recognition and subsequent signal transduction by RLRs.
Conserved domains of the class A scavenger receptors: evolution and function
Authors: Bowdish Dawn M. E. , Gordon Siamon
Published: December 2008

Summary:  The class A scavenger receptors are phagocytic pattern recognition receptors that are well represented in vertebrate genomes. The high level of conservation among vertebrates implies that this is an evolutionarily conserved family of receptors and indicates the presence of a common ancestral gene. The identity of this ancestral gene is not clear, as it appears that many of the domains of the scavenger receptors (e.g. collagenous, scavenger receptor cysteine rich) originated early in evolutionary history and are found in many combinations, often in genes of unknown function. These early receptors may function in cell–cell recognition, aggregation, or lipid recognition, and their involvement in pattern recognition, phagocytosis, and homeostasis may have been adaptations of such conserved patterns. Herein, we reclassify the class A scavenger receptors based on recent discoveries of new members of this family, describe the evolution of the various domains of the class A scavenger receptors, and discuss the appearance and function of these domains through evolutionary history.
Regulatory molecules required for nucleotide‐sensing Toll‐like receptors
Authors: Saitoh Shin‐Ichiroh , Miyake Kensuke
Published: December 2008

Summary: Toll‐like receptors (TLRs) play an important role in innate immune responses against bacteria and viruses. TLRs localize either on the cell surface or in intracellular vesicular compartments. The cell‐surface TLRs, including TLR1, TLR2, TLR4, and TLR6, recognize microbial membrane lipids, whereas TLR3, TLR7, TLR8, and TLR9 recognize pathogen‐derived nucleotides in intracellular compartments. TLR7 and TLR9 respond to host‐derived nucleotides as well, and they have been implicated in a variety of autoimmune diseases. Safety mechanisms are required to avoid detrimental autoimmune responses. TLR7 and TLR9 are sequestered in the endoplasmic reticulum (ER) in a resting state and traffic to endolysosomes upon ligand‐induced stimulation. Sequestration in the ER is a mechanism controlling TLR7/9 responses. A chaperone, gp96, in the ER is reported to regulate TLR7/9 maturation. gp96 is associated with TLR9 and is required for ligand‐induced activation of TLR7/9. Two molecules in the ER are reported to regulate TLR7/9 trafficking to endolysosomes. PRAT4A (a protein associated with TLR4 A) is associated with TLR9 and is required for ligand‐induced trafficking of TLR9 to endolysosomes. UNC93B1 is specifically associated with TLR3, TLR7, TLR9, and TLR13 and regulates ligand‐induced trafficking of TLR7 and TLR9 from the ER to endolysosomes. These molecules are potential therapeutic targets for controlling dysregulated TLR7/9 responses in autoimmune diseases.
Inflammasomes: guardians of cytosolic sanctity
Authors: Lamkanfi Mohamed , Dixit Vishva M.
Published: December 2008

Summary:  The innate immune system is critical in recognizing bacterial and viral infections to evoke a proper immune response. Certain members of the intracellular nucleotide‐binding and oligomerization domain (NOD)‐like receptor (NLR) family detect microbial components in the cytosol and trigger the assembly of large caspase‐1‐activating complexes termed inflammasomes. Autoproteolytic maturation of caspase‐1 zymogens within these inflammasomes leads to maturation and secretion of the pro‐inflammatory cytokines interleukin‐1β (IL‐1β) and IL‐18. The NLR proteins ICE protease‐activating factor (IPAF), NALP1b (NACHT domain‐, leucine‐rich repeat‐, and PYD‐containing protein 1b), and cryopyrin/NALP3 assemble caspase‐1‐activating inflammasomes in a stimulus‐dependent manner. Bacterial flagellin is sensed by IPAF, whereas mouse NALP1b detects anthrax lethal toxin. Cryopyrin/NALP3 mediates caspase‐1 activation in response to a wide variety of microbial components and in response to crystalline substances such as the endogenous danger signal uric acid. Genetic variations in Nalp1 and cryopyrin/Nalp3 are associated with autoinflammatory disorders and increased susceptibility to microbial infection. Further understanding of inflammasomes and their role in innate immunity should provide new insights into the mechanisms of host defense and the pathogenesis of autoimmune diseases.
Toll‐like receptor signaling in the lysosomal pathways
Authors: Sanjuan Miguel A. , Milasta Sandra , Green Douglas R.
Published: December 2008

Summary:  The lysosomal pathway digests material received by two main routes, phagocytosis and autophagy. Cells use phagocytosis to ingest extracellular particles by invaginations of the plasma membrane. In autophagy, a double membrane structure isolates portions of the cytoplasm to target it for degradation. During infection, phagocytes use both of these cellular functions to restrict microbial replication and at the same time to orchestrate an appropriate response against the invader. Toll‐like receptor recognition of a pathogen initiates an innate immune response against the pathogen that includes production of inflammatory cytokines, upregulation of costimulatory molecules to prime an adaptive immune response, and activation of phagocytosis and autophagy. Signaling through this family of receptors also produces a hybrid response in which proteins that participate in autophagy are recruited to phagosomes, resulting in expedited microbial elimination. In this review, we discuss recent views on how Toll‐like receptors direct microbes to final destruction by regulating the different pathways that lead to the lysosome.
Function of Nod‐like receptors in microbial recognition and host defense
Authors: Franchi Luigi , Warner Neil , Viani Kyle , Nuñez Gabriel
Published: December 2008

Summary:  Nucleotide oligomerization domain (NOD)‐like receptors (NLRs) are a specialized group of intracellular proteins that play a critical role in the regulation of the host innate immune response. NLRs act as scaffolding proteins that assemble signaling platforms that trigger nuclear factor‐κB and mitogen‐activated protein kinase signaling pathways and control the activation of inflammatory caspases. Importantly, mutations in several members of the NLR family have been linked to a variety of inflammatory diseases consistent with these molecules playing an important role in host–pathogen interactions and the inflammatory response. In this review, we focus on the role of Nod1 and Nod2 in host defense and in particular discuss recent finding regarding the role of Nlrc4, Nlpr1, and Nlrp3 inflammasomes in caspase‐1 activation and subsequent release of proinflammatory cytokines such as interleukin‐1β.
Structure and regulation of cytoplasmic adapter proteins involved in innate immune signaling
Authors: Monie Tom P. , Moncrieffe Martin C. , Gay Nicholas J.
Published: December 2008

Summary:  Initiation of the innate immune response requires agonist recognition by a pathogen recognition receptor. Following ligand binding, conformational rearrangement of the receptor creates a molecular scaffold from which signal transduction is propagated via complex cellular signaling pathways. This in turn leads to the induction of a pro‐inflammatory immune response. A critical component of these signaling pathways is the homotypic interaction of receptor and adapter proteins via specific protein interaction domains. Within the innate immune signaling cascade, homotypic interactions between members of the death domain family and the Toll/interleukin‐1 receptor domain are particularly important. Here we discuss the current understanding of the molecular basis of these homotypic receptor:adapter interactions and their role in innate immune signal transduction.
Ablation Behavior of a Three‐Dimensional Carbon/Silicon Carbide Composite Nozzle in an Ethanol/Oxygen Combustion Gas Generator
Authors: Chen Bo , Zhang Litong , Cheng Laifei , Luan Xingang
Published: December 2008

The ablation properties of a three‐dimensional carbon/silicon carbide composite nozzle were investigated via hot‐fire testing by an ethanol/oxygen combustion gas generator simulating combustion environments of the liquid rocket engine. The linear ablation rate at the nozzle throat was 0.250±0.023 mm/s, and the overall mass ablation rate was 0.246 kg/(m2 s). The ablation in the divergent section, convergent section, and in the regions near the throat grew severe by degree. Ablation mechanisms of the composite nozzle were predominated by the oxidation of the composite, and volatilization of the silica scale derived from oxidation of silicon carbide resulted in further ablation of the nozzle.
Design Guidelines for In‐Plane Mechanical Properties of SiC Fiber‐Reinforced Melt‐Infiltrated SiC Composites
Authors: Morscher Gregory N. , Pujar Vijay V.
Published: December 2008

In‐plane tensile stress–strain, tensile creep, and after‐creep retained tensile properties of melt‐infiltrated SiC–SiC composites reinforced with different fiber types were evaluated with an emphasis on obtaining simple or first‐order microstructural design guidelines for these in‐plane mechanical properties. Using the minimatrix approach to model stress–strain behavior and the results of this study, three basic general design criteria for stress and strain limits are formulated, namely a design stress limit, a design total strain limit, and an after‐creep design retained strength limit. It is shown that these criteria can be useful for designing components for high‐temperature applications.
Process Optimization in Tableware Industries Using Taguchi's Design of Experiments
Authors: Palm Birgit , Heinrich Jürgen G. , Reuer Joachim
Published: December 2008

The essential influences of 15 parameters on defects (cracks and bubbles) during production of tableware have been studied with 16 experimental progressions using a L16(215) experimental design by G. Taguchi. Evaluation (analysis of means and analysis of variance) indicated that in this production liter weight, drying time, moisture before biscuit firing, and position in the biscuit‐firing kiln have a significant influence on cracks. Concerning bubbles, parameters with an influence are liter weight, gate system, mold material, and moisture content before glost firing. Rejects of the article used in the experiments were reduced from 2.44% to 2.27% with respect to cracks and from 6.22% to 0% with respect to bubbles.
Flood insurance: from clients to global financial markets
Authors: Kron W.
Published: December 2008

Weather‐related natural catastrophes are increasing worldwide in number and intensity, and losses have reached new levels. This represents a challenge that must be faced by governments, the people concerned, and the financial sector, both nationally and globally. Flood insurance is rare in most countries, but the development of solutions to make flood risk more insurable has gained momentum. There is no ideal flood insurance scheme, as each situation is influenced by factors such as risk‐adequate premium structure, adverse selection, and general risk awareness. Solutions tailored to the situation in each respective country must be found. While rich countries have to find ways to handle record losses of US$100 bn and more, poor countries need micro‐insurance to provide people with at least a minimum of financial security. The insurance industry has – through the reinsurance sector – established a system to pay local monetary losses globally. In the wake of extremely expensive catastrophes, a system involving the whole financial market has great potential.
State‐level variation in conservation investment by a major nongovernmental organization
Authors: Fishburn Isla S. , Kareiva Peter , Gaston Kevin J. , Evans Karl L. , Armsworth Paul R.
Published: December 2008

Few empirical studies examine how conservation organizations distribute the resources that they have available for habitat conservation, despite numerous theoretical studies that recommend how these resources should be directed. Here we examine the distribution of conservation investments made over 49 years by a major conservation nongovernmental organization (NGO), The Nature Conservancy (TNC). We measured the level of conservation effort across U.S. states by the area protected and the upfront cost of protection, accounting for easements and land acquisitions. While correlated, we show that two measures of conservation effort (area and amount invested) cannot be used as reliable proxies for one another. The distributions of both measures of conservation effort are explained by combinations of one biological (species richness) and three socioeconomic (land price, rate of development and action of other NGOs) factors, revealing a generally strategic pattern of investment by TNC. Finally, we identify examples of underinvestment in particular states by TNC.
Reassessing the value of nursery areas to shark conservation and management
Authors: Kinney Michael John , Simpfendorfer Colin Ashley
Published: December 2008

Concern over declining shark populations has led to an intense interest in their conservation and management. Due to the difficulties involved in managing adult sharks, focus has been placed on young juvenile and neonate age classes that inhabit discrete inshore nursery areas. However, past confusion over what qualifies as a nursery habitat has led to the identification of vast coastal areas as nurseries, making conservation unfeasible. With the establishment of more discerning criteria for nursery area identification such concerns have been somewhat alleviated, but while effort has been put into defining, identifying, mapping, and in some cases protecting nursery areas, little attention has been paid to the practical value of nurseries for the recovery of exploited shark populations. Often neonate and young juveniles are considered the most critical age classes in terms of population stability/recovery, but evidence is mounting that suggests life stages outside the nursery may be more important in this regard. While nursery area protection should remain a component in shark management strategies it will be critical to link early life stage conservation with management strategies that encompass older individuals residing outside nurseries if effective management is to be achieved.
Establishment of a three‐dimensional co‐culture system by porcine hepatocytes and bone marrow mesenchymal stem cells in vitro
Authors: Gu Jinyang , Shi Xiaolei , Zhang Yue , Chu Xuehui , Hang Hualian , Ding Yitao
Published: December 2008

Aim:  The application of porcine hepatocytes in liver support systems has been hampered by the short‐term survival. Co‐cultivation of hepatocytes with non‐parenchymal cells may be beneficial for optimizing cell functions via heterotypic interactions. In this study, we present a new cultivation system of porcine hepatocytes and mesenchymal stem cells (MSCs) in a randomly distributed co‐culture manner.

Methods:  Mononuclear cells were isolated from bone marrow aspirate of swines (n = 3) by density gradient centrifugation. MSCs were characterized by flow cytometry with CD29, CD44, CD45 and CD90, respectively. Then freshly isolated hepatocytes were simultaneously inoculated with MSCs in a hepatocyte dominant manner. The morphological and functional changes of heterotypic interactions were characterized.

Results:  Ninety percent MSCs of passage 3 were positive for CD29, CD44 and CD90, but negative for CD45. A rapid attachment and self‐organization of three‐dimensional hepatocyte aggregates were encouraged. The cell ultrastructure indicating heterotypic junctions remained similar to that of hepatocytes in vivo. Fluorescence microscopy further verified that MSCs served as a feeder layer for hepatocyte aggregates. Hepatocyte performance levels such as albumin secretion, urea synthesis and CYP3A1 induction were all significantly enhanced in co‐culture group compared with hepatocyte homo‐culture (P < 0.05). The best hepatic function levels were achieved on day 2 and moderately decreased in the following co‐culture days. Moreover, the cell cycle of hepatocytes manifested the same trend in parallel to the enhancement of hepatocyte functionality.

Conclusions:  A three‐dimensional co‐culture system by porcine hepatocytes and bone marrow MSCs was for the first time established in vitro. Enhanced liver‐specific functions make such a co‐culture system a promising tool for tissue engineering, cell biology, and bioartificial liver devices.
Selective CB1 cannabinoid receptor antagonist, SR141716A, attenuates liver injury induced by Concanavalin A
Authors: Kojima Midori , Kato Naoto , Hirano Daisuke , Ochi Takashi , Nii Aisuke , Shinjo Katsuhiro , Eda Hiroyuki
Published: December 2008

Aim:  The aim of this study was to investigate the hepatoprotective activity of a selective cannabinoid receptor 1 (CB1) antagonist, SR141716A, in a Concanavalin A (Con A)‐induced mouse liver injury model and to determine whether SR141716A has an effect on the production of inflammatory cytokines and chemokines induced by Con A.

Results:  Injection of Con A (20 mg/kg) to mice developed hepatitis determined by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation and necrosis in the liver. Pretreatment with SR141716A (30 mg/kg) significantly reduced plasma AST and ALT level, protected against necrosis in the liver, and significantly reduced plasma cytokine and chemokine levels, including TNFα, IFN‐γ, CXCL9, MIP1‐α, and IL‐10 and no change decreased in IL‐4.

Conclusions:  The selective CB1 antagonist, SR141716A, exerts a hepatoprotective effect on Con A‐induced liver injury in mice by attenuating the increase in cytokine and chemokine levels and inhibiting hepatocyte injury. These findings raise the possibility of using CB1 antagonists as anti‐inflammatory drugs for treating hepatitis as well as other inflammatory diseases.