Extracellular cell stress (heat shock) proteins - immune responses and disease: an overview

Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory ‘danger signals’ for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells. The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals/non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining/regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins, therefore, form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease

Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model

Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH) and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA) resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs. © 2011 Yang et al

Das Verhalten von Plasmopara viticola auf resistenten und anfälligen Rebsorten

An Topfreben und Blattscheiben verschiedener resistenter und anfälliger Rebsorten wurde das Verhalten von Plasmopara viticola bei verschiedenen Inokulumdichten, unterschiedlicher Temperatur und Beleuchtung während der Inkubation, sowie veränderter Inkubationsdauer und Blattnässedauer geprüft.Einen starken Einfluß auf die Sporulation des Pilzes auf Blattscheiben hatten die Konzentration des Inokulums sowie die Temperatur und die Belichtung während der Inkubation. Bei diesen Faktoren traten signifikante Interaktionen mit der Sorte auf. Die Dauer der Blattnässe war, soweit sie die für eine Infektion notwendige Dauer nicht unterschritt, ohne Einfluß auf die Sporulation des Pilzes bei verschiedenen Sorten. Ähnliches gilt für die Inkubationsdauer, deren Verlängerung, auch weit über die minimal erforderliche Zeit hinaus, ohne Einfluß auf die Sporulation blieb.The behavior of Plasmopara viticola on resistant and susceptible grapevine varietiesThe behaviour of Plasmopara viticola with respect to inoculum concentration, temperature, level of illumination during incubation, duration of incubation and leaf wetness was investigated with different resistant und susceptible grapevine varieties using leaf discs and potted plants. Inoculum concentration, temperature and illumination during incubation had a great effect on the sporulation of the fungus on leaf discs and proved to be cultivar-dependent. Duration of leaf wetness had no effect on sporulation provided that it was long enough for the infection process to be completed. In a similar way an incubation time longer than that necessary for completion of fungal growth, had no effect on sporulation

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Wirtsbesiedlung durch Plasmopara viticola bei unterschiedlich anfälligen Wirten

Mit Plasmopara viticola infizierte Blattscheiben von verschieden anfalligen Rebsorten und Rebarten wurden nach 6, 24 und 48 h Inkubation fixiert und mit optischen Aufhellern oder Säurefuchsinlösung gefärbt. Die in den Blattscheiben vorgefundenen Entwicklungsstadien des Erregers wurden quantitativ ausgewertet.Die Resistenz einer Rebsorte hat keinen Einfluß auf die Anlagerung der Zoosporen von P. viticola an ihre Spaltöffnungen. Die ersten Behinderungen der Wirtsbesiedlung an resistenten Arten traten auf, wenn der Keimschlauch des Erregers versucht, in die Atemhöhle einzudringen. Bei den verschiedenen Klonen der Arten Vitis riparia und V. rupestris gelang es P. viticola häufig nicht, in der Atemhöhle sichtbare Strukturen zu bilden. Bei V. riparia und der pilzresistenten Sorte Fr 946-60 wurde die Erregerentwicklung in der Atemhöhle häufig schon vor der Bildung des Primärhaustoriums behindert. Bei den pilzresistenten Sorten Fr 946-60, Fr 993-60, Castor und SV 5-276 wurde der Erreger meist nach der Bildung eines Haustoriums in der weiteren Entwicklung behindert . In diesem Entwicklungsstadium kam es häufig zu Degenerationserscheinungen an der befallenen Wirtszelle. Bei der Sorte Pollux traten diese Behinderungen später, meist nach Bildung des zweiten Haustoriums, auf.Host settlement of Plasmopara viticola on different susceptible hostsLeaf discs of grapevine varieties and species of various resistance to downy mildew were infected by Plasmopara viticola, fixed after 6, 24 and 48 h of incubation and coloured with optical brighteners or fuchsin acid solution. The different stages of infection were investigated qualitatively and quantitatively. Zoospores of P. viticola settled at the stomata of leaves of resistant and susceptible cultivars. The first phenomenon of resistance occurs when the germination tube tries to enter the substomatal hole. In clones of Vitis riparia and V. rupestris germination tubes of the pathogen were frequently hindered to enter the substomatal hole. In V. riparia and the resistant variety Fr 946-60 P. viticola was often already stopped before forming a primary haustorium. In the resistant varieties Fr 946-60, Fr 993-60, Castor and SV 5-276 the pathogen was stopped in many cases after the formation of the first haustorium. At this time degeneration of the parasitized host-cells could often be observed. In the resistant variety Pollux cell degenerations mostly occur after the formation of the secondary haustorium

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Gasless balloon laparoscopy

The concept of balloon laparoscopy (B-LSC) pursues the simplification of conventional diagnostic laparoscopy (LSC). The pneumoperitoneum is replaced by a transparent balloon, which is positioned in front of the optical system. It shall be shown that with this arrangement diagnostic LSC can be performed outside of the operating room without requiring general anesthesia.An inflatable balloon was developed for a 30°/3.5-mm rod lens. Intra-abdominally the balloon was expanded to a diameter of 30 mm by air insufflation, and B-LSC was performed. Twelve patients were examined in general anesthesia before laparoscopic surgery. Twelve patients were subjected to B-LSC fully awake or with sedation (midazolam or propofol/S-ketamine) as a “second-look” procedure by way of a flexible trocar (port) left in the abdominal wall at the end of previous operation. Eight patients have been first provided with a trocar under sedation (midazolam or propofol/S-ketamine) combined with local anesthesia, and B-LSC was performed before laparoscopic surgery.On a scale of 1–5, the general impression was rated 1.9, the navigability to the different abdominal organs 2.5, the resolution 1.5, the stability of the system optic/trocar 2.1, the suitability of the balloon format 1.9, and the stability of the balloon against lateral shear forces 2.4. The degree of painfulness of the examination was rated 2.8, the tolerance of the port 1.4, and the degree of painfulness of trocar placement at 2.5. On a scale of 1 to 3, the strain of the abdominal musculature was rated 1.4 and the obstruction by adhesions 1.7.B-LSC is technically practicable with good imaging qualities and without requiring pneumoperitoneum. It is tolerated in great extent under slight sedation and particularly well under deep sedation. The procedure is suitable for diagnostics of unclear abdominal conditions, as a second-look LSC and also as a staging LSC

Exosomes Communicate Protective Messages during Oxidative Stress; Possible Role of Exosomal Shuttle RNA

BACKGROUND: Exosomes are small extracellular nanovesicles of endocytic origin that mediate different signals between cells, by surface interactions and by shuttling functional RNA from one cell to another. Exosomes are released by many cells including mast cells, dendritic cells, macrophages, epithelial cells and tumour cells. Exosomes differ compared to their donor cells, not only in size, but also in their RNA, protein and lipid composition. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that exosomes, released by mouse mast cells exposed to oxidative stress, differ in their mRNA content. Also, we show that these exosomes can influence the response of other cells to oxidative stress by providing recipient cells with a resistance against oxidative stress, observed as an attenuated loss of cell viability. Furthermore, Affymetrix microarray analysis revealed that the exosomal mRNA content not only differs between exosomes and donor cells, but also between exosomes derived from cells grown under different conditions; oxidative stress and normal conditions. Finally, we also show that exposure to UV-light affects the biological functions associated with exosomes released under oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results argue that the exosomal shuttle of RNA is involved in cell-to-cell communication, by influencing the response of recipient cells to an external stress stimulus

Follicular Dendritic Cell-Specific Prion Protein (PrPc) Expression Alone Is Sufficient to Sustain Prion Infection in the Spleen

Prion diseases are characterised by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. Following peripheral exposure high levels of prion-specific PrPSc accumulate first upon follicular dendritic cells (FDC) in lymphoid tissues before spreading to the CNS. Expression of PrPC is mandatory for cells to sustain prion infection and FDC appear to express high levels. However, whether FDC actively replicate prions or simply acquire them from other infected cells is uncertain. In the attempts to-date to establish the role of FDC in prion pathogenesis it was not possible to dissociate the Prnp expression of FDC from that of the nervous system and all other non-haematopoietic lineages. This is important as FDC may simply acquire prions after synthesis by other infected cells. To establish the role of FDC in prion pathogenesis transgenic mice were created in which PrPC expression was specifically “switched on” or “off” only on FDC. We show that PrPC-expression only on FDC is sufficient to sustain prion replication in the spleen. Furthermore, prion replication is blocked in the spleen when PrPC-expression is specifically ablated only on FDC. These data definitively demonstrate that FDC are the essential sites of prion replication in lymphoid tissues. The demonstration that Prnp-ablation only on FDC blocked splenic prion accumulation without apparent consequences for FDC status represents a novel opportunity to prevent neuroinvasion by modulation of PrPC expression on FDC