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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.

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.)

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.)

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.)

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.

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.

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.

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.