Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC)is the third most frequent virus-associated human malignancy. How this tumor escapes immune recognition despite the expression of several viral antigens has remained poorly understood. Our previous in vitro studies have shown that NPC cells release exosomes containing high amounts of galectin-9, a ligand of the membrane receptor Tim-3, which is able to induce apoptosis in mature Th1 lymphocytes.Here, we sought to determine whether galectin-9-carrying exosomes were produced in NPC patients and whether such exosomes might play a role in the immune evasion of NPC cells. We report that galectin-9-containing exosomes are selectively detected in plasma samples from NPC patients and mice xenografted with NPC tumors. The incorporation into exosomes protects galectin-9 against proteolytic cleavage but retains its Tim-3-binding capacity. Importantly, NPC exosomes induce massive apoptosis in EBVspecific CD4 ؉ cells used as a model of target T cells. This effect is inhibited by both anti-Tim-3 and antigalectin-9 blocking antibodies. These results indicate that blocking galectin-9/Tim-3 interaction in vivo might alleviate the Th1-suppressive effect of NPC exosomes and sustain antitumoral T-cell responses and thereby improve clinical efficacy of immunotherapeutic approaches against NPC. (Blood. 2009;113:1957-1966 IntroductionNasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy and the third most frequent virus-associated human malignancy after hepatocarcinomas and cervix carcinomas. Each year, approximately 80 000 new cases are diagnosed worldwide. The geographic distribution of NPC is not uniform. It is relatively rare in European and North American countries. Very high incidence foci are found in South China, especially in Guandong and Guangxi provinces (25-40 per 100 000 per year). 1 Areas of intermediate incidence (approximately 3-8 per 100 000 per year) include a large number of developing or emerging countries, especially in North and Central Africa (Tunisia, Algeria, Morocco, Somalia, and Kenya) and in Southeast Asia (Philippines, Vietnam, Indonesia).NPC is an epithelial malignancy with a complex etiology involving viral, environmental, and hereditary factors. Except for some very rare cases of atypical highly differentiated NPC occurring in Western countries, the intact EBV genome is always contained in the nuclei of all malignant cells. 2,3 Many of the approximately 80 EBV genes are silent, but several viral RNAs and proteins are consistently expressed in NPC and contribute to the malignant phenotype. 4 NPC oncogenesis also requires a variable assortment of cellular genetic or epigenetic alterations. 5 Another important biologic feature of NPC is the presence of a massive lymphoid infiltrate in the primary tumor. This infiltrate contains mostly T lymphocytes and a minority of B cells, monocytes, dendritic cells, and eosinophils. The abundant production by malignant NPC cells of inflammatory cytokines, including interle...

Influenza virus still poses a major threat to human health. Despite widespread vaccination programmes and the development of drugs targeting essential viral proteins, the extremely high mutation rate of influenza virus still leads to the emergence of new pathogenic virus strains. Therefore, it has been suggested that cellular cofactors that are essential for influenza virus infection might be better targets for antiviral therapy. It has previously been reported that influenza virus efficiently infects Epstein-Barr virus-immortalized B cells, whereas Burkitt's lymphoma cells are virtually resistant to infection. Using this cellular system, it has been shown here that an active NF-kB signalling pathway is a general prerequisite for influenza virus infection of human cells. Cells with low NF-kB activity were resistant to influenza virus infection, but became susceptible upon activation of NF-kB. In addition, blocking of NF-kB activation severely impaired influenza virus infection of otherwise highly susceptible cells, including the human lung carcinoma cell lines A549 and U1752 and primary human cells. On the other hand, infection with vaccinia virus was not dependent on an active NF-kB signalling pathway, demonstrating the specificity of this pathway for influenza virus infection. These results might be of major importance for both the development of new antiviral therapies and the understanding of influenza virus biology.

BackgroundA so called “taxonomic impediment” has been recognized as a major obstacle to biodiversity research for the past two decades. Numerous remedies were then proposed. However, neither significant progress in terms of formal species descriptions, nor a minimum standard for descriptions have been achieved so far. Here, we analyze the problems of traditional taxonomy which often produces keys and descriptions of limited practical value. We suggest that phylogenetics and phenetics had a subtle and so far unnoticed effect on taxonomy leading to inflated species descriptions.DiscussionThe term “turbo-taxonomy” was recently coined for an approach combining cox1 sequences, concise morphological descriptions by an expert taxonomist, and high-resolution digital imaging to streamline the formal description of larger numbers of new species. We propose a further development of this approach which, together with open access web-publication and automated pushing of content from journal into a wiki, may create the most efficient and sustainable way to conduct taxonomy in the future. On demand, highly concise descriptions can be gradually updated or modified in the fully versioned wiki-framework we use. This means that the visibility of additional data is not compromised, while the original species description -the first version- remains preserved in the wiki, and of course in the journal version. A DNA sequence database with an identification engine replaces an identification key, helps to avoid synonyms and has the potential to detect grossly incorrect generic placements. We demonstrate the functionality of a species-description pipeline by naming 101 new species of hyperdiverse New Guinea Trigonopterus weevils in the open-access journal ZooKeys.SummaryFast track taxonomy will not only increase speed, but also sustainability of global species inventories. It will be of great practical value to all the other disciplines that depend on a usable taxonomy and will change our perception of global biodiversity. While this approach is certainly not suitable for all taxa alike, it is the tool that will help to tackle many hyperdiverse groups and pave the road for more sustainable comparative studies, e.g. in community ecology, phylogeography and large scale biogeographic studies.

The Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics) was developed to provide accurate, reliable detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated sensitivity, specificity, cross-reactivity, and agreement with a vesicular stomatitis virus-based pseudo-neutralisation assay for the Elecsys Anti-SARS-CoV-2 immunoassay. Sensitivity and agreement between the Elecsys Anti-SARS-CoV-2 immunoassay and pseudo-neutralisation assay measurements were evaluated using samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection, a majority of whom were hospitalised. Specificity was evaluated using samples from routine diagnostic testing/blood donors collected pre-December 2019 and thus deemed negative for SARS-CoV-2-specific antibodies. Cross-reactivity was evaluated using samples containing a wide range of potentially cross-reacting analytes, purchased from commercial vendors. For sensitivity and specificity, point estimates and 95% confidence intervals (CIs) were calculated. Agreement between the Elecsys Anti-SARS-CoV-2 immunoassay and pseudo-neutralisation assay was calculated. Sensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay in patients with prior PCR-confirmed SARS-CoV-2 infection was 99.5% (95% CI 97.0–100.0) at ≥14 days post-PCR confirmation. Overall specificity (n=10,453) was 99.80% (99.69–99.88). Only 4/792 samples containing potential cross-reacting analytes were reactive with the Elecsys Anti-SARS-CoV-2 immunoassay, resulting in an overall specificity in this cohort of 99.5% (98.6–99.9). Positive, negative and overall agreement (n=46) between Elecsys Anti-SARS-CoV-2 immunoassay and a pseudo-neutralisation assay were 86.4% (73.3–93.6), 100% (34.2–100) and 87.0% (74.3–93.9), respectively. The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated high sensitivity (99.5% at ≥14 days post-PCR confirmation) and specificity (99.80%), supporting its use as a tool for identification of past SARS-CoV-2 infection, including in populations with low disease prevalence.

Background Trigonopterus weevils are widely distributed throughout Melanesia and hyperdiverse in New Guinea. They are a dominant feature in natural forests, with narrow altitudinal zonation. Their use in community ecology has been precluded by the “taxonomic impediment”.Methodology/Principal FindingsWe sampled >6,500 specimens from seven areas across New Guinea; 1,002 specimens assigned to 270 morphospecies were DNA sequenced. Objective clustering of a refined dataset (excluding nine cryptic species) at 3% threshold revealed 324 genetic clusters (DNA group count relative to number of morphospecies = 20.0% overestimation of species diversity, or 120.0% agreement) and 85.6% taxonomic accuracy (the proportion of DNA groups that “perfectly” agree with morphology-based species hypotheses). Agreement and accuracy were best at an 8% threshold. GMYC analysis revealed 328 entities (21.5% overestimation) with 227 perfect GMYC entities (84.1% taxonomic accuracy). Both methods outperform the parataxonomist (19% underestimation; 31.6% taxonomic accuracy). The number of species found in more than one sampling area was highest in the Eastern Highlands and Huon (Sørensen similarity index 0.07, 4 shared species); ⅓ of all areas had no species overlap. Success rates of DNA barcoding methods were lowest when species showed a pronounced geographical structure. In general, Trigonopterus show high α and β-diversity across New Guinea.Conclusions/SignificanceDNA barcoding is an excellent tool for biodiversity surveys but success rates might drop when closer localities are included. Hyperdiverse Trigonopterus are a useful taxon for evaluating forest remnants in Melanesia, allowing finer-grained analyses than would be possible with vertebrate taxa commonly used to date. Our protocol should help establish other groups of hyperdiverse fauna as target taxa for community ecology. Sequencing delivers objective data on taxa of incredible diversity but mostly without a solid taxonomic foundation and should help pave the road for the eventual formal naming of new species.

A species discovery and description pipeline to accelerate and improve taxonomy is outlined, relying on concise expert descriptions, combined with DNA sequencing, digital imaging, and automated wiki species page creation from the journal. One hundred and one new species of Trigonopterus Fauvel, 1862 are described to demonstrate the feasibility of this approach: Trigonopterus aeneipennis sp. n., Trigonopterus aeneus sp. n., Trigonopterus agathis sp. n., Trigonopterus agilis sp. n., Trigonopterus amplipennis sp. n., Trigonopterus ancoruncus sp. n., Trigonopterus angulatus sp. n., Trigonopterus angustus sp. n., Trigonopterus apicalis sp. n., Trigonopterus armatus sp. n., Trigonopterus ascendens sp. n., Trigonopterus augur sp. n., Trigonopterus balimensis sp. n., Trigonopterus basalis sp. n., Trigonopterus conformis sp. n., Trigonopterus constrictus sp. n., Trigonopterus costatus sp. n., Trigonopterus costicollis sp. n., Trigonopterus crassicornis sp. n., Trigonopterus cuneipennis sp. n., Trigonopterus cyclopensis sp. n., Trigonopterus dentirostris sp. n., Trigonopterus discoidalis sp. n., Trigonopterus dromedarius sp. n., Trigonopterus durus sp. n., Trigonopterus echinus sp. n., Trigonopterus edaphus sp. n., Trigonopterus eremitus sp. n., Trigonopterus euops sp. n., Trigonopterus ferrugineus sp. n., Trigonopterus fusiformis sp. n., Trigonopterus glaber sp. n., Trigonopterus gonatoceros sp. n., Trigonopterus granum sp. n., Trigonopterus helios sp. n., Trigonopterus hitoloorum sp. n., Trigonopterus imitatus sp. n., Trigonopterus inflatus sp. n., Trigonopterus insularis sp. n., Trigonopterus irregularis sp. n., Trigonopterus ixodiformis sp. n., Trigonopterus kanawiorum sp. n., Trigonopterus katayoi sp. n., Trigonopterus koveorum sp. n., Trigonopterus kurulu sp. n., Trigonopterus lekiorum sp. n., Trigonopterus lineatus sp. n., Trigonopterus lineellus sp. n., Trigonopterus maculatus sp. n., Trigonopterus mimicus sp. n., Trigonopterus monticola sp. n., Trigonopterus montivagus sp. n., Trigonopterus moreaorum sp. n., Trigonopterus myops sp. n., Trigonopterus nangiorum sp. n., Trigonopterus nothofagorum sp. n., Trigonopterus ovatus sp. n., Trigonopterus oviformis sp. n., Trigonopterus parumsquamosus sp. n., Trigonopterus parvulus sp. n., Trigonopterus phoenix sp. n., Trigonopterus plicicollis sp. n., Trigonopterus politoides sp. n., Trigonopterus pseudogranum sp. n., Trigonopterus pseudonasutus sp. n., Trigonopterus ptolycoides sp. n., Trigonopterus punctulatus sp. n., Trigonopterus ragaorum sp. n., Trigonopterus rhinoceros sp. n., Trigonopterus rhomboidalis sp. n., Trigonopterus rubiginosus sp. n., Trigonopterus rubripennis sp. n., Trigonopterus rufibasis sp. n., Trigonopterus scabrosus sp. n., Trigonopterus scissops sp. n., Trigonopterus scharfi sp. n., Trigonopterus signicollis sp. n., Trigonopterus simulans sp. n., Trigonopterus soiorum sp. n., T sordidus sp. n., Trigonopterus squamirostris sp. n., Trigonopterus striatus sp. n., Trigonopterus strigatus sp. n., Trigonopterus strombosceroides sp. n., Trigonopterus subgla...

Weevils (Curculionoidea) comprise one of the most diverse groups of organisms on earth. There is hardly a vascular plant or plant part without its own species of weevil feeding on it and weevil species diversity is greater than the number of fishes, birds, reptiles, amphibians and mammals combined. Here, we employ ultraconserved elements (UCEs) designed for beetles and a novel partitioning strategy of loci to help resolve phylogenetic relationships within the radiation of Australasian smurf-weevils (Eupholini). Despite being emblematic of the New Guinea fauna, no previous phylogenetic studies have been conducted on the Eupholini. In addition to a comprehensive collection of fresh specimens, we supplement our taxon sampling with museum specimens, and this study is the first target enrichment phylogenomic dataset incorporating beetle specimens from museum collections. We use both concatenated and species tree analyses to examine the relationships and taxonomy of this group. For species tree analyses we present a novel partitioning strategy to better model the molecular evolutionary process in UCEs. We found that the current taxonomy is problematic, largely grouping species on the basis of similar color patterns. Finally, our results show that most loci required multiple partitions for nucleotide rate substitution, suggesting that single partitions may not be the optimal partitioning strategy to accommodate rate heterogeneity for UCE loci.

The Sunda Arc forms an almost continuous chain of islands and thus a potential dispersal corridor between mainland Southeast Asia and Melanesia. However, the Sunda Islands have rather different geological histories, which might have had an important impact on actual dispersal routes and community assembly. Here, we reveal the biogeographical history of hyperdiverse and flightless Trigonopterus weevils. Different approaches to ancestral area reconstruction suggest a complex east to west range expansion. Out of New Guinea, Trigonopterus repeatedly reached the Moluccas and Sulawesi transgressing Lydekker′s Line. Sulawesi repeatedly acted as colonization hub for different segments of the Sunda Arc. West Java, East Java and Bali are recognized as distinct biogeographic areas. The timing and diversification of species largely coincides with the geological chronology of island emergence. Colonization was not inhibited by traditional biogeographical boundaries such as Wallace’s Line. Rather, colonization patterns support distance dependent dispersal and island age limiting dispersal.