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We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the solar system, exploring the transient optical sky, and mapping the Milky Way. LSST will be a large, wide-field ground-based system designed to obtain repeated images covering the sky visible from Cerro Pachón in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg 2 field of view, a 3.2-gigapixel camera, and six filters (ugrizy) covering the wavelength range 320-1050 nm. The project is in the construction phase and will begin regular survey operations by 2022. About 90% of the observing time will be devoted to a deep-wide-fast survey mode that will uniformly observe a 18,000 deg 2 region about 800 times (summed over all six bands) during the anticipated 10 yr of operations and will yield a co-added map to r ∼27.5. These data will result in databases including about 32 trillion observations of 20 billion galaxies and a similar number of stars, and they will serve the majority of the primary science programs. The remaining 10% of the observing time will be allocated to special projects such as Very Deep and Very Fast time domain surveys, whose details are currently under discussion. We illustrate how the LSST science drivers led to these choices of system parameters, and we describe the expected data products and their characteristics.

Background: HIV patients on protease inhibitors have greater risk of acute coronary syndromes (ACS) but little is known about treatment-naïve patients. Methods and Results: Authors conducted a prospective single-center study from Soweto, South Africa, comparing the clinical and angiographic features of treatment-naïve HIV positive and negative patients with ACS. Between March 2004 and February 2008, 30 consecutive treatment-naïve HIV patients with ACS were compared to the next HIV-negative patient as a 1:1 control. HIV patients were younger (43 +/- 7 vs. 54 +/- 13, P = 0.004) and, besides smoking (73% vs. 33%, P = 0.002), had fewer risk factors than the control group with less hypertension (23% vs. 77%, P = 0.0001), diabetes (3% vs. 23%, P = 0.05), LDL hyperlipidemia (2.2 +/- 0.9 vs. 3.0 +/- 1.2, P = 0.006), and other coronary risk factors (7% vs. 53%, P = 0.0001). HDL was lower in the HIV group (0.8 +/- 0.3 vs. 1.1 +/- 0.4, P = 0.001). Atherosclerotic burden was lower in the HIV group with more normal infarct-related arteries (47% vs. 13%, P = 0.005) but a higher degree of large thrombus burden (43% vs. 17%, P = 0.02). Stents were used to a similar degree in HIV and control patients (30% vs. 37%, P = 0.78) with more target lesion revascularization in the HIV group (56% vs. 0%, P = 0.008). Conclusion: Treatment-naïve HIV patients with ACS are younger and have fewer traditional risk factors than HIV-negative patients. HIV patients have less atherosclerotic but higher thrombotic burden which may imply a prothrombotic state in the pathogenesis of ACS in these patients. [ABSTRACT FROM AUTHOR]

Objective: This review will map the literature on the types of research and methods used to investigate the wound-healing properties of Stryphnodendron adstringens ( barbatimão ) in skin and mucosa injuries., Introduction: Barbatimão is a Brazilian native plant and its wound-healing properties have been described in literature since the colonial period. It is one of the 71 plants included in the Brazilian health system's national list of medicinal plants of interest. However, existing literature reviews on the subject are limited, not comprehensive, lack a search strategy, and lack peer review., Inclusion Criteria: This scoping review will include all types of published and unpublished sources that investigate the wound-healing properties of barbatimão to treat any type of skin or mucosa injury in humans, animals, or in vitro, in any context., Methods: A scoping review will be conducted following JBI methodology. The main databases to be searched will include Embase (EBSCOhost), CINAHL (EBSCOhost), Scopus, PubMed (EBSCOhost), ScienceDirect, Lilacs, SciELO, CUIDEN, MOSAICO, Web of Science, Epistemonikos, and Google Scholar. Unpublished studies will also be considered. Two independent reviewers will examine titles and abstracts and select and read full-text sources for possible inclusion. Subsequently, the reviewers will extract and synthesize the data, which will be presented as a map, diagram, or table, according to the review objectives., Review Registration: Open Science Framework osf.io/w57m4., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 JBI.)

Concerted, timely action for mitigating climate change is of uttermost importance to keep global warming as close to 1.5°C as possible. Air traffic already plays a strong role in driving climate change and is projected to grow-with only limited technical potential for decarbonizing this means of transport. Therefore, it is desirable to minimize the expansion of air traffic or even facilitate a reduction in affluent countries. Effective policies and behavioral change, especially among frequent flyers, can help to lower greenhouse gas emissions. For both, a positive evaluation and public support is indispensable. This study contributes to understanding air travel behavior and the perception of regulative policies. We examined the role of attitudes, perceived behavioral control, efficacy, global identity, and justice concerns for intentions to avoid flights and aviation-related environmental policy support. We conducted an online survey study with a quota sample of N = 2,530 participants in Germany. The strongest positive predictors of intentions to refrain from flying and policy support were perceived behavioral control to travel without flying, efficacy beliefs that avoiding air travel contributes to climate change mitigation, and intergenerational justice concerns; pro-travel attitude was a negative predictor. Moreover, we tested whether the provision of additional information on climate impact, global and intranational inequalities as well as subsidies (implying intranational inequality) affected the intention to avoid air travel and policy support. We found no effects of the different types of information. Nor did we find an interaction between the type of information provided and global or national identity. Our results highlight the need for a shift within the mobility sector that facilitates attractive and accessible transport alternatives in order to strengthen people's behavioral control to choose other means than planes and their efficacy perceptions. Moreover, raising awareness of the impacts of climate change on future generations and developing strategies to promote people's concern for intergenerational justice might motivate people to reduce air travel and thereby contribute to a livable future for new generations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Berneiser, Becker and Loy.)

Background: The use of augmented reality (AR) is growing in medical education, in particular, in radiology and surgery. AR has the potential to become a strategic component of neurosurgical training courses. In fact, over the years, there has been a progressive increase in the application of AR in the various fields of neurosurgery. In this study, the authors aim to define the diffusion of these augmented reality systems in recent years. This study describes future trends in augmented reality for neurosurgeons., Methods: A systematic review of the literature was conducted to identify research published from December 1st, 2011 to November 30th, 2021. Electronic databases (PubMed, PubMed Central, and Scopus) were screened. The methodological quality of studies and extracted data were assessed for "augmented reality" and "neurosurgery". The data analysis focused on the geographical distribution, temporal evolution, and topic of augmented reality in neurosurgery., Results: A total of 198 studies have been included. The number of augmented reality applications in the neurosurgical field has increased during the last 10 years. The main topics on which it is mostly applied are spine surgery, neuronavigation, and education. The geographical distribution shows extensive use of augmented reality in the USA, Germany, China, and Canada. North America is the continent that uses augmented reality the most in the training and education of medical students, residents, and surgeons, besides giving the greatest research contribution in spine surgery, brain oncology, and surgical planning. AR is also extensively used in Asia for intraoperative navigation. Nevertheless, augmented reality is still far from reaching Africa and other countries with limited facilities, as no publications could be retrieved from our search., Conclusions: The use of AR is significantly increased in the last 10 years. Nowadays it is mainly used in spine surgery and for neurosurgical education, especially in North America, Europe and China. A continuous growth, also in other aspects of the specialty, is expected in the next future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cannizzaro, Zaed, Safa, Jelmoni, Composto, Bisoglio, Schmeizer, Becker, Pizzi, Cardia and Servadei.)

Emerging evidence have been supporting the idea that the better known South Atlantic coral reefs (located between 18°S and 24°S) are now essentially senescent structures that have experienced little or no additional vertical reef growth over the past millennia. This has often coincided with a shift to a dominance of non-coral calcifying organisms becoming the main CaCO 3 producers in these high latitude and marginal marine settings. Here, we used Calcification Accretion Units (CAUs) and census-based methods to measure non-coral rates of CaCO 3 production on the geologically senescent reef and adjacent rhodolith beds within the southernmost subtropical Atlantic reef (i.e., Queimada Grande Reef, QGR). The reef habitat is currently producing CaCO 3 at rates of ∼126 g m -2 yr -1 . In contrast, fragments of dead corals skeletons deposited adjacent to the reef over the last ∼2000 years are now colonized by crustose coralline red algae. These form a rhodolith bed that produces CaCO 3 at rates of 858 g m -2 yr -1 . Our results indicate that, whilst not sufficient to promote active net framework accumulation, CaCO 3 production by coralline algae and bryozoans on the QGR appears to be sufficient to at least limit net large-scale erosion of the underlying reef structure, allowing the reef structure to persist in a state close to budgetary stasis. Finally, our results are also of relevance for providing insights regarding the balance of CaCO 3 production/dissolution/erosion processes in coral reefs, especially in these less understood marginal reefs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Soluble MER has emerged as a potential biomarker for delayed resolution of inflammation after myocardial injury and a therapeutic target to reduce cardiac-related morbidity and mortality in adults. The significance of soluble MER in pediatric populations, however, is unclear. We sought to investigate if soluble MER concentrations change in response to myocardial ischemia and reperfusion injury in pediatric patients. In parallel, we also sought to investigate for correlations between the change in soluble MER concentration and specific patient, bypass, and postoperative data., Design: We quantified the change in plasma soluble MER concentration post- compared with precardiopulmonary bypass for each patient in a cohort of pediatric patients. Linear regression, correlation coefficients, and t tests were used to compare innate patient characteristics (i.e., sex, age, cyanotic vs acyanotic cardiac lesion), cardiac bypass data (i.e., total cardiac bypass time, total aortic cross-clamp time, perioperative steroid administration), and postcardiac bypass data (total postoperative ventilator days, total postoperative vasoactive medication days, and total postoperative ICU days) with change in soluble MER concentrations., Setting: Whole blood samples were obtained intraoperatively at a single tertiary care children's hospital from April to October 2019., Subjects: Our patient cohort included 24 pediatric patients ages ranging from birth to 19 years old with both cyanotic and acyanotic cardiac lesions., Interventions: Retrospective analyses of pediatric blood specimens, as well as patient, bypass, and postoperative data, were performed., Measurements and Main Results: We observed a statistically significant increase in soluble MER concentration post cardiac bypass in 17 of 24 patients (71%)., Conclusions: Soluble MER concentrations increase with cardiopulmonary bypass-induced inflammation and myocardial ischemia and reperfusion injury in pediatric patients. The utility of soluble MER as a clinical biomarker to identify pediatric patients at risk for exacerbated postoperative outcomes after bypass-induced myocardial ischemia and reperfusion injury requires further investigation., Competing Interests: Dr. Becker received internal grant support from a Pediatric Critical Care Fellow Research Award through Ann & Robert H. Lurie Children’s Hospital of Chicago. Mr. Lantz is supported by the National Institutes of Health (NIH) T32 GM008061. Dr. Thorp is supported by NIH R01-HL122309, HL139812, and P01AI112522. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Cell migration is an essential process in health and in disease, including cancer metastasis. A comprehensive inventory of migration factors is nonetheless lacking-in part due to the difficulty in assessing migration using high-throughput technologies. Hence, there are currently very few screens that systematically reveal factors controlling cell migration. Here, we introduce MigExpress as a platform for the 'identification of Migration control genes by differential Expression'. MigExpress exploits the combination of in-depth molecular profiling and the robust quantitative analysis of migration capacity in a broad panel of samples and identifies migration-associated genes by their differential expression in slow- versus fast-migrating cells. We applied MigExpress to investigate non-small cell lung cancer (NSCLC), which is the most frequent cause of cancer mortality mainly due to metastasis. In 54 NSCLC cell lines, we comprehensively determined mRNA and protein expression. Correlating the transcriptome and proteome profiles with the quantified migration properties led to the discovery and validation of FLNC, DSE, CPA4, TUBB6, and BICC1 as migration control factors in NSCLC cells, which were also negatively correlated with patient survival. Notably, FLNC was the least expressed filamin in NSCLC, but the only one controlling cell migration and correlating with patient survival and metastatic disease stage. In our study, we present MigExpress as a new method for the systematic analysis of migration factors and provide a comprehensive resource of transcriptomic and proteomic data of NSCLC cell lines related to cell migration., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The class of circular RNA (circRNA) is characterized by head-to-tail bonds between exons formed by backsplicing. Here, we provide a resource of circRNA expression in a comprehensive panel of 60 lung cancer and non-transformed cell lines (FL3C dataset). RNA sequencing after depletion of ribosomal RNA quantified the expression of circRNA and linear RNA. We detected 148,811 circular RNAs quantified by 2.8 million backsplicing reads originating from 12,251 genes. The number of identified circRNAs was markedly higher using rRNA depletion compared to public polyA-enriched RNA-seq datasets. CircRNAs almost never started in the first exon nor ended in the last exon and started more frequently in earlier exons. Most circRNAs showed high cell line specificity and correlated positively with their linear RNA counterpart. Known cancer genes produced more circRNAs than non-cancer genes. Subsets of circRNAs correlated with cell proliferation, histological subtype or genotype. CircTNFRSF21 was translated crossing the backsplice site in two different reading frames. Overexpression of circPVT1 , circERBB2 , circHIPK3 , circCCNB1 , circSMAD2 , circTNFRSF21 and circKIF5B significantly increased colony formation. In conclusion, our data provide a comprehensive map of circRNA expression in lung cancer cells and global patterns of circRNA production as a useful resource for future research into lung cancer circRNAs.

Lung cancer continues to be the leading cause of cancer-related deaths worldwide, with little improvement in patient survival rates in the past decade. Long non-coding RNAs (lncRNAs) are gaining importance as possible biomarkers with prognostic potential. By large-scale data mining, we identified LINC00261 as a lncRNA which was significantly downregulated in lung cancer. Low expression of LINC00261 was associated with recurrence and poor patient survival in lung adenocarcinoma. Moreover, the gene pair of LINC00261 and its neighbor FOXA2 were significantly co-regulated. LINC00261 as well as FOXA2 negatively correlated with markers for epithelial-to-mesenchymal transition (EMT) and were suppressed by the EMT inducer TGFβ. Hierarchical clustering of gene expression data from lung cancer cell lines could further verify the association of high LINC00261 / FOXA2 expression to an epithelial gene signature. Furthermore, higher expression of the LINC00261 / FOXA2 locus was associated with lung cancer cell lines with lower migratory capacity. All these data establish LINC00261 and FOXA2 as an epithelial-specific marker pair, downregulated during EMT and lung cancer progression, and associated with lower cell migration potential in lung cancer cells.

Seasonal epidemics of influenza A virus are a major cause of severe illness and are of high socio-economic relevance. For the design of effective antiviral therapies, a detailed knowledge of pathways perturbed by virus infection is critical. We performed comprehensive expression and organellar proteomics experiments to study the cellular consequences of influenza A virus infection using three human epithelial cell lines derived from human lung carcinomas: A549, Calu-1 and NCI-H1299. As a common response, the type I interferon pathway was up-regulated upon infection. Interestingly, influenza A virus infection led to numerous cell line-specific responses affecting both protein abundance as well as subcellular localization. In A549 cells, the vesicular compartment appeared expanded after virus infection. The composition of autophagsomes was altered by targeting of ribosomes, viral mRNA and proteins to these double membrane vesicles. Thus, autophagy may support viral protein translation by promoting the clustering of the respective molecular machinery in autophagosomes in a cell line-dependent manner., (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)

The development of parasitic nematodes proceeds via multiple stages, often implicating the necessity to adapt to different environments. Especially the transition from free-living to parasitic stages is accompanied by a significant change in the environmental conditions. To shed light on possible adaptations to these transitions, the fatty acid composition of different developmental stages of the bovine lungworm Dictyocaulus viviparus was investigated. Fatty acids of D. viviparus eggs, the free-living first, second and third larval stage (L1-L3) as well as the parasitic preadult stage and adult male and female worms residing in the lungs of infected hosts were quantified by gas chromatography after transesterification to their fatty acid methyl esters. The fatty acid content and diversity were higher in parasitic stages compared to those of free-living larvae. The most prevalent fatty acids in both parasitic and free-living stages were stearic (C18:0), palmitic (C16:0), palmitoleic (C16:1) and caprylic acid (C8:0). A variety of (poly-)unsaturated FAs was found in the parasitic stages and in the eggs, which was similar to the variety of FAs found in bovine surfactant. This finding indicates that parasitic stages of D. viviparus take up FAs from their environment. While eggs contained the highest concentration of fatty acids, a decrease was observed from eggs to L1 and further from L2 to L3. The lowest concentration was found in 38-days-old L3, which suggests that FAs serve as an energy reserve for the free-living, non-feeding larval stages. The free-living larvae contained mainly saturated fatty acids and only traces of unsaturated fatty acids, which is in contrast to the phospholipid saturation hypothesis of cold tolerance. Instead, a trade-off between desiccation stress and temperature adaptation may favour a higher amount of saturated FAs in the free-living larval stages. Further studies explicitly examining the FA composition of the different classes of lipids are necessary to better describe the adaptative responses of the FA metabolism to different environmental conditions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Macroautophagy is regarded as a nonspecific bulk degradation process of cytoplasmic material within the lysosome. However, the process has mainly been studied by nonspecific bulk degradation assays using radiolabeling. In the present study we monitor protein turnover and degradation by global, unbiased approaches relying on quantitative mass spectrometry-based proteomics. Macroautophagy is induced by rapamycin treatment, and by amino acid and glucose starvation in differentially, metabolically labeled cells. Protein dynamics are linked to image-based models of autophagosome turnover. Depending on the inducing stimulus, protein as well as organelle turnover differ. Amino acid starvation-induced macroautophagy leads to selective degradation of proteins important for protein translation. Thus, protein dynamics reflect cellular conditions in the respective treatment indicating stimulus-specific pathways in stress-induced macroautophagy.

Despite being overexpressed in different tumor entities, RIO kinases are hardly characterized in mammalian cells. We investigated the role of these atypical kinases in different cancer cells. Using isogenic colon-, breast- and lung cancer cell lines, we demonstrate that knockdown of RIOK1, but not of RIOK2 or RIOK3, strongly impairs proliferation and invasiveness in conventional and 3D culture systems. Interestingly, these effects were mainly observed in RAS mutant cancer cells. In contrast, growth of RAS wildtype Caco-2 and Bcr-Abl-driven K562 cells is not affected by RIOK1 knockdown, suggesting a specific requirement for RIOK1 in the context of oncogenic RAS signaling. Furthermore, we show that RIOK1 activates NF-κB signaling and promotes cell cycle progression. Using proteomics, we identified the pro-invasive proteins Metadherin and Stathmin1 to be regulated by RIOK1. Additionally, we demonstrate that RIOK1 promotes lung colonization in vivo and that RIOK1 is overexpressed in different subtypes of human lung- and breast cancer. Altogether, our data suggest RIOK1 as a potential therapeutic target, especially in RAS-driven cancers., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Coproscopical methods used in veterinary-parasitological diagnostics were validated according to their sensitivity (Se) and egg recovery rate [efficiency (Ef)]. Validation of the combined sedimentation-flotation method and the modified McMaster method was performed by using feces spiked with eggs of Ancylostoma caninum, Uncinaria stenocephala, Cooperia oncophora, cyathostomins, Ascaris suum, Toxascaris leonina, Toxocara canis, Trichuris vulpis, Moniezia expansa, and Anoplocephala perfoliata. For validation of the sedimentation method, Fasciola hepatica eggs were used. With the combined sedimentation-flotation method using ZnSO4 as flotation medium [specific gravity (SG) 1.30], 5 g fecal samples of all tested parasite species (concentration levels 1, 5, 10, 20, 40, 60, and 80 epg) were reproducibly detected "positive" (100 % Se) as of 80 epg. The Ef of the combined sedimentation-flotation method, defined as percentage of rediscovered eggs, revealed clear differences between parasites and showed the highest value for cyathostomins and the lowest for U. stenocephala and T. leonina eggs. The average Ef for all parasite species at 80 epg was 1.50 %. With the McMaster method (concentration levels 1, 30, 50, 80, 100, 500, and 1000 epg), all tested parasite species were detected reliably positive as of 500 epg with a mean Ef of 46.4 %. When evaluating the sedimentation method (concentration levels 1, 5, 10, 15, 20, 25, and 30 epg), F. hepatica eggs were reproducibly found in 5 g fecal samples as of 20 epg with 20.0 % Ef. The result that the combined zinc sulfate sedimentation-flotation method (SG 1.30) as flotation medium provides diagnostic certainty only as of 80 epg has to be considered at preventing zoonoses. If pet owners wish to prevent any zoonotic infection ("zero tolerance"), a monthly anthelminthic treatment should be advised instead of monthly fecal examinations.

The macroautophagy machinery has been implicated in MHC class II restricted antigen presentation. Here, we report that this machinery assists in the internalization of MHC class I molecules. In the absence of the autophagy factors Atg5 and Atg7, MHC class I surface levels are elevated due to decreased endocytosis and degradation. Internalization of MHC class I molecules occurs less efficiently if AAK1 cannot be recruited via Atg8/LC3B. In the absence of Atg-dependent MHC class I internalization, dendritic cells stimulate CD8(+) T cell responses more efficiently in vitro and in vivo. During viral infections, lack of Atg5 results in enhanced influenza- and LCMV-specific CD8(+) T cell responses in vivo. Elevated influenza-specific CD8(+) T cell responses are associated with better immune control of this infection. Thus, the macroautophagy machinery orchestrates T cell immunity by supporting MHC class II but compromises MHC class I restricted antigen presentation., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Intercellular communication between parasites and with host cells provides mechanisms for parasite development, immune evasion, and disease pathology. Bloodstream African trypanosomes produce membranous nanotubes that originate from the flagellar membrane and disassociate into free extracellular vesicles (EVs). Trypanosome EVs contain several flagellar proteins that contribute to virulence, and Trypanosoma brucei rhodesiense EVs contain the serum resistance-associated protein (SRA) necessary for human infectivity. T. b. rhodesiense EVs transfer SRA to non-human infectious trypanosomes, allowing evasion of human innate immunity. Trypanosome EVs can also fuse with mammalian erythrocytes, resulting in rapid erythrocyte clearance and anemia. These data indicate that trypanosome EVs are organelles mediating non-hereditary virulence factor transfer and causing host erythrocyte remodeling, inducing anemia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Under conditions of nutrient shortage autophagy is the primary cellular mechanism ensuring availability of substrates for continuous biosynthesis. Subjecting cells to starvation or rapamycin efficiently induces autophagy by inhibiting the MTOR signaling pathway triggering increased autophagic flux. To elucidate the regulation of early signaling events upon autophagy induction, we applied quantitative phosphoproteomics characterizing the temporal phosphorylation dynamics after starvation and rapamycin treatment. We obtained a comprehensive atlas of phosphorylation kinetics within the first 30 min upon induction of autophagy with both treatments affecting widely different cellular processes. The identification of dynamic phosphorylation already after 2 min demonstrates that the earliest events in autophagy signaling occur rapidly after induction. The data was subjected to extensive bioinformatics analysis revealing regulated phosphorylation sites on proteins involved in a wide range of cellular processes and an impact of the treatments on the kinome. To approach the potential function of the identified phosphorylation sites we performed a screen for MAP1LC3-interacting proteins and identified a group of binding partners exhibiting dynamic phosphorylation patterns. The data presented here provide a valuable resource on phosphorylation events underlying early autophagy induction.

Autophagy is one of the two major degradation pathways within eukaryotic cells. Nevertheless, little is known about the protein composition of autophagosomes, the vesicles shuttling proteins to lysosomes for degradation. Protein correlation profiling in combination with stable isotope labeling by amino acids in cell culture is a stringent method to investigate the dynamics of the autophagosomal proteome. It enables the discrimination between autophagosomal and co-purifying proteins identifying organellar candidate proteins for further investigation.

Antigen preservation for presentation is a hallmark of potent antigen-presenting cells. In this paper, we report that in human macrophages and dendritic cells, a subset of phagosomes gets coated with Atg8/LC3, a component of the molecular machinery of macroautophagy, and maintains phagocytosed antigens for prolonged presentation on major histocompatibility complex class II molecules. These Atg8/LC3-positive phagosomes are formed around the antigen with TLR2 agonists and require reactive oxygen species production by NOX2 for their generation. A deficiency in the NOX2-dependent formation of these antigen storage phagosomes could contribute to compromise antifungal immune control in chronic granulomatous disease patients.

New movement traits reflecting unfavorable movement characteristics were defined on the basis of detailed movement evaluations (DME) of warmblood foals and mares performed in connection with regular breeding events of the Oldenburg horse breeding societies in 2009 and 2010. DME information was available for 3374 foals and 2844 mares and used for correlation analyses with conformation information on 1987 mares from studbook inspections (SBI) in 2009 and performance information on 2758 mares from mare performance tests (MPT) in 2000 to 2008. Analyses of variance revealed few significant differences between scores for SBI and MPT traits in mares without and with indications of imbalance (IMB) in general or specific findings like irregular tail tone or posture (TTP). SBI scores for general impression and development were significantly lower and MPT scores for trot under rider tended to be higher in IMB-positive mares. Genetic parameters were estimated in linear animal models with residual maximum likelihood. Additive genetic correlations and Pearson correlation coefficients between univariately predicted breeding values indicated unfavorable genetic correlations of IMB and TTP with dressage-related conformation and performance traits. For SBI and MPT traits, we found similarities between the correlation patterns for DME traits in foals and mares. The results implied that breeding of dressage horses may benefit from revision of current movement evaluation and consideration of specific movement characteristics.

Detailed movement evaluations of warmblood foals and mares were performed in connection with regular breeding events of the Oldenburg horse breeding societies in 2009 and 2010. Unfavourable movement characteristics considered indicative for impaired balance were noted by a special judge (SJ) and the regular judges of the breeding events (RJ) and served as the basis for definition of new movement traits. Detailed movement information on 3374 foals and 2844 mares showed that more severe findings like irregular motion pattern in hind legs or irregularity in general motion pattern occurred only sporadically (prevalences of 1-2%). Irregular tail tone or posture was documented for 4% of the foals and 5% of the mares, resulting in prevalences of the comprehensive trait indications of imbalance (IMB) of 6.2% (foals) and 5.5% (mares). Binary coding was used for all traits, and genetic parameters were estimated bivariately in linear animal models with residual maximum likelihood. Comparative analyses between judges revealed that differences between trait definitions of SJ and RJ were larger in the mares than in the foals, but justified combined use of SJ and RJ information in both age groups. Heritability estimates for the movement traits ranged on the original scale from 0.02 to 0.26 in the foals and from 0.03 to 0.12 in the mares, with heritabilities for IMB on the underlying liability scale of 0.46 (foals) and 0.22 (mares). Comparative analyses between age groups indicated that common genetic factors may be responsible for findings of impaired balance in foals and mares. The results implied that horse breeding may benefit from using the early available information on the movement of foals obtained by detailed movement evaluations, although favourable combination of foal and mare data in future genetic evaluations may require refined recording of unfavourable movement characteristics in the adult horses., (© 2011 Blackwell Verlag GmbH.)

Significance: Protein degradation has been identified as being deregulated in numerous human diseases. Hence, proteins involved in proteasomal as well as lysosomal degradation are regarded as interesting potential drug targets and are thoroughly investigated in clinical studies., Recent Advances: Technical advances in the field of quantitative mass spectrometry (MS)-based proteomics allow for detailed investigations of protein degradation dynamics and identifications of responsible protein-protein interaction networks enabling a systematic analysis of the degradative inventory of the cell and its underlying molecular mechanisms., Critical Issues: In the current review we outline recent technical advances and their limitations in MS-based proteomics and discuss their use for the analysis of protein dynamics involved in degradation processes., Future Directions: In the next years the analysis of crosstalk between different posttranslational modifications (PTMs) will be a major focus of MS-based proteomics studies. Increasing evidence highlights the complexity of PTMs with positive and negative feedbacks being discovered. In this regard, the generation of absolute quantitative proteomic data will be essential for theoretical scientists to construct predictive network models that constitute a valuable tool for fast hypothesis testing and for explaining underlying molecular mechanisms.

To get an overview of the current state of endoparasite prevalences in stray and not well-cared dogs and cats, faecal samples of 445 stray and foster dogs and 837 stray and foster cats were collected at their arrival at animal shelters in Lower Saxony (Germany). They were investigated for infections with endoparasites by the use of sedimentation-flotation method. Additionally, 341 canine and 584 feline samples were investigated by IDEXX SNAP® Giardia test. Stages of endoparasites were found coproscopically in 9.4 % (n = 42) of the canine samples, 4.0 % were positive for Toxocara canis, 0.9 % for hookworms, 0.4 % for Toxascaris leonina and 0.2 % for Hammondia-like oocysts. Giardia-coproantigen was detected in 11.4 % of the canine samples. In cats, 33.6 % (n = 281) were coproscopically positive for helminths and/or protozoa. Toxocara cati was found in 27.1 %, Isospora spp. in 7.5 %, Capillaria spp. 5.0 %, Taeniidae in 2.0 %, hookworms in 1.1 %, Giardia sp. in 0.7 %, Aelurostrongylus abstrusus in 1.0 % and Toxoplasma-like oocysts in 0.1 %. Coproantigen specific for Giardia sp. was detected in 6.8 % of the feline samples. Dogs and cats up to 1 year of age were more frequently infected with endoparasites than animals over 1 year of age (p < 0.001). Toxocara spp. and Isospora spp. were detected significantly more often in younger dogs and cats, respectively (p < 0.05 and p < 0.001). Stray dogs or cats older than 1 year were significantly more frequently infected with endoparasites than dropped off animals of the same age group (p < 0.05). Using the faecal egg count reduction test, the therapeutic efficacy of some anthelmintics was tested. All tested anthelmintics showed high efficacy and no suspected anthelmintic resistance was found. However, endoparasite-infected stray and free-roaming cats and dogs may contribute considerably to the contamination of public parks, playgrounds and sandpits with zoonotic parasites and therefore have to be considered a public health problem.

A hallmark of macroautophagy is the formation of autophagosomes, double-membrane vesicles that enwrap cellular components destined for lysosomal degradation. We examined autophagosomal protein dynamics under various inducing stimuli using a comprehensive mass spectrometry-based proteomics approach in combination with functional studies in yeast and human cell cultures. Time frame and stimuli type influenced the autophagosome proteome, underlining the dynamic constitution of the organelle. We identified both a core set of proteins always localizing to autophagosomes and stimulus-dependent components that will serve as a resource for further characterization of the autophagosomal machinery and cargo selection. Among the core proteins were newly discovered autophagy regulators found to be conserved from yeast to humans, as well as the proteasome.

Autophagy is one of the major intracellular catabolic pathways, but little is known about the composition of autophagosomes. To study the associated proteins, we isolated autophagosomes from human breast cancer cells using two different biochemical methods and three stimulus types: amino acid deprivation or rapamycin or concanamycin A treatment. The autophagosome-associated proteins were dependent on stimulus, but a core set of proteins was stimulus-independent. Remarkably, proteasomal proteins were abundant among the stimulus-independent common autophagosome-associated proteins, and the activation of autophagy significantly decreased the cellular proteasome level and activity supporting interplay between the two degradation pathways. A screen of yeast strains defective in the orthologs of the human genes encoding for a common set of autophagosome-associated proteins revealed several regulators of autophagy, including subunits of the retromer complex. The combined spatiotemporal proteomic and genetic data sets presented here provide a basis for further characterization of autophagosome biogenesis and cargo selection.

Background: HIV infection is associated with a high prevalence of antiphospholipid antibodies (aPL) and increased thrombotic events but the aetiopathogenic link between the two is unclear., Findings: Prospective single centre study from Soweto, South Africa, comparing the prevalence of aPL in highly active anti-retroviral therapy (HAART) naïve HIV positive and negative patients presenting with Acute Coronary Syndromes (ACS). Between March 2004 and February 2008, 30 consecutive black South African HIV patients with ACS were compared to 30 black HIV negative patients with ACS. The HIV patients were younger (43 ± 7 vs. 54 ± 13, p = 0.004) and besides smoking (73% vs. 33%, p = 0.002) and lower HDL levels (0.8 ± 0.3 vs. 1.1 ± 0.4, p = 0.001) had fewer risk factors than the control group. HIV patients had a higher prevalence of anticardiolipin (aCL) IgG (47% vs. 10%, p = 0.003) and anti-prothrombin (aPT) IgG antibodies (87% vs. 21%, p < 0.001) but there was no difference in the prevalence of the antiphospholipid syndrome (44% vs. 24%, p = N/S) and aPL were not predictive of clinical or angiographic outcomes., Conclusions: Treatment naïve black South African HIV patients with ACS are younger with fewer traditional coronary risk factors than HIV negative patients but have a higher prevalence and different expression of aPL which is likely to be an epiphenomenon of the HIV infection rather than causally linked to thrombosis and the pathogenesis of ACS.

Late endosomes and lysosomes (hereafter referred to as lysosomes) play an essential role in the turnover of cellular macromolecules and organelles. Their biochemical characterization has so far depended on purification methods based on either density gradient centrifugations or magnetic purification of iron-loaded organelles. Owing to dramatic changes in lysosomal density and stability associated with lysosomal diseases and cancer, these methods are not optimal for the comparison of normal and pathological lysosomes. Here, we introduce an efficient method for the purification of intact lysosomes by magnetic immunoprecipitation with antibodies against the vacuolar-type H(+) -ATPase. Quantitative MS-based proteomics analysis of the obtained lysosomal membranes identified 60 proteins, most of which have previously been associated with the lysosomal compartment. Interestingly, the lysosomal membrane proteome was significantly altered by the ectopic expression of an active form of the ErbB2 oncogene, which renders the cells highly metastatic. The furthermost ErbB2-associated changes included increased levels of CD63, S100A11 and ferritin heavy chain. Overall, our data introduce the antibody-based purification of lysosomes as a suitable method for the characterization of lysosomes from a variety of pathological conditions with altered lysosomal density and stability., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Patients with human immunodeficiency virus (HIV) infection on protease inhibitors (PIs) have a heightened risk of arterial thrombosis but little is known about treatment-naive patients., Methods/results: Prospective study from South Africa comparing thrombotic profiles of HIV-positive and -negative patients with acute coronary syndrome (ACS). A total of 30 treatment-naive HIV-positive patients with ACS were compared to 30 HIV-negative patients with ACS. Patients with HIV were younger; and besides smoking (73% vs 33%) and low high-density lipoprotein (HDL; 0.8 ± 0.3 vs 1.1 ± 0.4), they had fewer risk factors. Thrombophilia was more common in HIV-positive patients with lower protein C (PC; 82 ± 22 vs 108 ± 20) and higher factor VIII levels (201 ± 87 vs 136 ± 45). Patients with HIV had higher frequencies of anticardiolipin (aCL; 47% vs 10%) and antiprothrombin antibodies (87% vs 21%)., Conclusion: Treatment-naive HIV-positive patients with ACS are younger, with fewer traditional risk factors but a greater degree of thrombophilia compared with HIV-negative patients.

Dendrimers are synthetically built macromolecules that, through the conjugation of various functional moieties, have become the basis of the emerging field of nanomedicine. However, research is beginning to show that the dynamic interactions between PAMAM dendrimers and cellular lipid membranes can stimulate membrane hole formation and expansion. These membrane disruptions are not unique to dendrimers and are the observed functions of natural proteins such as MSI-78 (pexiganan) and Trans-Activator of Transcription protein (TAT). Membrane interactions can also affect the dendrimers, causing structural deformations and encapsulation within a lipid bilayer vesicle. Acetamide capping of the positively charged PAMAM terminal end groups neutralizes the dendrimer, and many of these effects can be minimized or eliminated. Knowledge gained from these studies will indeed have an impact on the future designs of dendrimer-based nanodevices.

Aim: Aim of the study was the evaluation of early predictive parameters of event-free survival (not listed for liver transplantation, not transplanted, no death) in children suffering from biliary atresia after hepatoportoenterostomy (Kasai procedure) in order to optimize pretransplant management., Patients and Methods: Sixty-seven infants were treated with the Kasai operation at our institution over a 20-year period from 1978 until 1998. Median age at time of operation was 51 days after birth (range 19 - 180 days). Of these 67 infants, 24 children with complete datasets and an observation time of at least one year were evaluated retrospectively using a Cox regression model. The response variable was event-free survival after a median observation time of 4.9 years (1.11- 10.37 years). Six variables were entered as covariates: alanine aminotransferase (ALAT), cholinesterase activity, bilirubin, age at the time of Kasai operation and tracer excretion and uptake during hepatobiliary scintigraphy (HBSS). All variables were evaluated six weeks after operation. For subsequent cut-off determination, a receiver operating analysis (ROC analysis) was carried out., Results: Tracer excretion shown by HBSS showed the highest prognostic power to predict event-free survival after Kasai operation (log rank 18.68, p < 0.0001) followed by bilirubin and ALAT as further significant parameters in the first univariate step of the Cox regression model. In the subsequent multivariate step, the prognostic power of HBSS was improved only by bilirubin (log rank 24.6, p < 0.0001). The ROC analysis determined a cut-off for bilirubin concentrations of 57 micromol/l for event-free survival with a sensitivity of 80 % and a specificity of 78.6 %. The five-year event-free survival-rate was 100 % in the group with good tracer excretion and a bilirubin concentration of 57 micromol/l and 27 % for the other group (log rank test, p < 0. 0001)., Conclusion: Early predictors of success of the Kasai operation in children with biliary atresia are free tracer excretion as shown by HBSS and a serum bilirubin concentration < 57 micromol/l six weeks after the operation. Thus, children with bilirubin concentrations above this level should be carefully and frequently monitored with regard to a transplantation requirement in order to optimize pretransplant management.

The nature of dark matter remains mysterious, with luminous material accounting for at most approximately 25 per cent of the baryons in the Universe. We accordingly undertook a survey looking for the microlensing of stars in the Large Magellanic Cloud (LMC) to determine the fraction of Galactic dark matter contained in massive compact halo objects (MACHOs). The presence of the dark matter would be revealed by gravitational lensing of the light from an LMC star as the foreground dark matter moves across the line of sight. The duration of the lensing event is the key observable parameter, but gives non-unique solutions when attempting to estimate the mass, distance and transverse velocity of the lens. The survey results to date indicate that between 8 and 50 per cent of the baryonic mass of the Galactic halo is in the form of MACHOs (ref. 3), but removing the degeneracy by identifying a lensing object would tighten the constraints on the mass in MACHOs. Here we report a direct image of a microlens, revealing it to be a nearby low-mass star in the disk of the Milky Way. This is consistent with the expected frequency of nearby stars acting as lenses, and demonstrates a direct determination of a lens mass from a microlensing event. Complete solutions such as this for halo microlensing events will probe directly the nature of the MACHOs.

Objective: To determine the effect of desensitization of the laryngeal mucosal mechanoreceptors on upper airway mechanics in exercising horses., Animals: 6 Standardbreds., Procedure: In study 1, videoendoscopic examinations were performed while horses ran on a treadmill with and without topical anesthesia of the laryngeal mucosa. In study 2, peak tracheal and nasopharyngeal pressures and airflows were obtained from horses during incremental treadmill exercise tests, with and without topical anesthesia of the laryngeal mucosa. A nasal occlusion test was performed on each horse while standing during an endoscopic examination for both trials., Results: In study 1, horses had nasopharyngeal collapse while running on the treadmill when the laryngeal mucosa was anesthetized. In study 2, inspiratory upper airway and nasopharyngeal impedance were significantly higher, and peak tracheal inspiratory pressure, respiratory frequency, and minute ventilation were significantly lower in horses when the laryngeal mucosa was anesthetized, compared with values obtained when horses exercised without topical anesthesia. Peak inspiratory and expiratory airflows were lower in horses when the laryngeal mucosa was anesthetized, although differences did not quite reach significance (P = 0.06 and 0.09, respectively). During a nasal occlusion test, horses had episodes of nasopharyngeal collapse and dorsal displacement of the soft palate when the laryngeal mucosa was anesthetized. Upper airway function was normal in these horses without laryngeal mucosal anesthesia., Conclusions and Clinical Relevance: Receptors within the laryngeal mucosa may be important in maintaining upper airway patency in exercising horses.