Extinct or extant? A new species of \u3ci\u3eTermitodius\u3c/i\u3e Wasmann, 1894, (Coleoptera: Scarabaeidae: Aphodiinae: Rhyparini) with a short review of the genus

A new species of Termitodius Wasmann (Coleoptera: Scarabaeidae: Aphodiinae: Rhyparini) is de­scribed from Colombia, Termitodius woodruffi Skelley, Clavijo-Bustos, and Keller, new species. This species is both extant and abundantly preserved in copal. The genus Termitodius is reviewed with a key and brief accounts to all species. Una nueva especie de Termitodius Wasmann (Coleoptera: Scarabaeidae: Aphodiinae: Rhyparini) es descrita de Colombia, Termitodius woodruffi Skelley, Clavijo-Bustos, y Keller, nueva especie. Esta especie es existente y abundantemente preservada en copal. El género Termitodius es revisado con una clave y reseñas breves para todas las especies. The pantropical tribe Rhyparini is represented in the Neotropical region by six genera and 25 species. Of these six genera, only one genus, Rhyparus Westwood, is distributed both in the eastern and western hemispheres, the remaining five are exclusively from America (Schoolmeesters 2021; Skelley 2021a, b). The genus Termitodius Wasmann was described in 1894 for a new species from Venezuela (Wasmann 1894). Since then, the only taxo­nomic treatments were the description of two new species 40 years ago (Reyes-Castillo and Martínez 1979) and its generic delimitation (Skelley 2007). Though more than 30 fossil species of Aphodiinae are known from the Mesozoic and Tertiary period of the Cenozoic Era, none belong to the tribe Rhyparini nor to the Neotropical region (Krell 2007). Most of the described Neotropical Scarabaeoidea fossils are preserved in amber from the Dominican Republic (e.g., Ratcliffe and Ocampo 2001; Ocampo 2002, 2006; Woodruff 2009; Poinar 2014). Members of the Rhyparini have been documented in Dominican amber (Wu 1996; Poinar and Poinar 1999; Krell 2007) that were recently described (Skelley 2021a, b). Other insects in the New World were described from more recent resin deposits like Colom­bian copal. However, the age of Colombian pieces lack consensus, with the current trend attributing it to the Cenozoic quaternary period (e.g., Hinojosa-Díaz and Engel 2007; Azar et al. 2009; Penney et al. 2013a; Poinar et al. 2017). Also, it is curious that many described species from copal inclusions are considered to be extant species, yet remain to be discovered as living specimens (Penney et al. 2013b). The earliest published report that identifies the Colombian copal specimens as Termitodius is by Penney and Green (2011), who called it a “subfossil”. However, Robert Woodruff began working on this new species in the early 2000s, but declining health and other events forced the project to be postponed. After deciding to describe this species to honor Woodruff, PES studied available modern specimens to document unreported specimens of all species in this rare genus. He borrowed a specimen identified by P. Reyes as “T. coronatus” from Colombia, that was later identified as a new species by O. L. Cartwright. Close examination found it to be most similar to the copal specimens in morphology and distribution, and not T. coronatus. This led to the following generic review and species description

The conservation status of the world's freshwater molluscs

With the biodiversity crisis continuing unchecked, we need to establish levels and drivers of extinction risk, and reassessments over time, to effectively allocate conservation resources and track progress towards global conservation targets. Given that threat appears particularly high in freshwaters, we assessed the extinction risk of 1428 randomly selected freshwater molluscs using the IUCN Red List Categories and Criteria, as part of the Sampled Red List Index project. We show that close to one-third of species in our sample are estimated to be threatened with extinction, with highest levels of threat in the Nearctic, Palearctic and Australasia and among gastropods. Threat levels were higher in lotic than lentic systems. Pollution (chemical and physical) and the modification of natural systems (e.g. through damming and water abstraction) were the most frequently reported threats to freshwater molluscs, with some regional variation. Given that we found little spatial congruence between species richness patterns of freshwater molluscs and other freshwater taxa, apart from crayfish, new additional conservation priority areas emerged from our study. We discuss the implications of our findings for freshwater mollusc conservation, the adequacy of a sampled approach and important next steps to estimate trends in freshwater mollusc extinction risk over time

A quantitative global review of species population monitoring

Abstract: Species monitoring, defined here as the repeated, systematic collection of data to detect long‐term changes in the populations of wild species, is a vital component of conservation practice and policy. We created a database of nearly 1200 schemes, ranging in start date from 1800 to 2018, to review spatial, temporal, taxonomic, and methodological patterns in global species monitoring. We identified monitoring schemes through standardized web searches, an online survey of stakeholders, in‐depth national searches in a sample of countries, and a review of global biodiversity databases. We estimated the total global number of monitoring schemes operating at 3300–15,000. Since 2000, there has been a sharp increase in the number of new schemes being initiated in lower‐ and middle‐income countries and in megadiverse countries, but a decrease in high‐income countries. The total number of monitoring schemes in a country and its per capita gross domestic product were strongly, positively correlated. Schemes that were active in 2018 had been running for an average of 21 years in high‐income countries, compared with 13 years in middle‐income countries and 10 years in low‐income countries. In high‐income countries, over one‐half of monitoring schemes received government funding, but this was less than one‐quarter in low‐income countries. Data collection was undertaken partly or wholly by volunteers in 37% of schemes, and such schemes covered significantly more sites and species than those undertaken by professionals alone. Birds were by far the most widely monitored taxonomic group, accounting for around half of all schemes, but this bias declined over time. Monitoring in most taxonomic groups remains sparse and uncoordinated, and most of the data generated are elusive and unlikely to feed into wider biodiversity conservation processes. These shortcomings could be addressed by, for example, creating an open global meta‐database of biodiversity monitoring schemes and enhancing capacity for species monitoring in countries with high biodiversity. Article impact statement: Species population monitoring for conservation purposes remains strongly biased toward a few vertebrate taxa in wealthier countries

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5?mg/kg i.v. 3 weekly for 1?year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56?years (range 18-88?years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5?years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P?=?0.78). At 5?years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P?=?0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P?=?0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P?=?0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P?=?0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Averting biodiversity collapse in tropical forest protected areas

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon¹⁻³. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses⁴⁻⁹. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world’s major tropical regions. Our analysis reveals great variation in reserve ‘health’: about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.Keywords: Ecology, Environmental scienc

Extinct or extant? A new species of Termitodius Wasmann, 1894, (Coleoptera: Scarabaeidae: Aphodiinae: Rhyparini) with a short review of the genus

A new species of Termitodius Wasmann (Coleoptera: Scarabaeidae: Aphodiinae: Rhyparini) is described from Colombia, Termitodius woodruffi Skelley, Clavijo-Bustos, and Keller, new species. This species is both extant and abundantly preserved in copal. The genus Termitodius is reviewed with a key and brief accounts to all species.Una nueva especie de Termitodius Wasmann (Coleoptera: Scarabaeidae: Aphodiinae: Rhyparini) es descrita de Colombia, Termitodius woodruffi Skelley, Clavijo-Bustos, y Keller, nueva especie. Esta especie es existente y abundantemente preservada en copal. El género Termitodius es revisado con una clave y reseñas breves para todas las especies

ASTX660, an antagonist of cIAP1/2 and XIAP, increases antigen processing machinery and can enhance radiation-induced immunogenic cell death in preclinical models of head and neck cancer

Inhibitor of apoptosis protein (IAP) antagonists have shown activity in preclinical models of head and neck squamous cell carcinoma (HNSCC), and work across several cancer types has demonstrated diverse immune stimulatory effects including enhancement of T cell, NK cell, and dendritic cell function. However, tumor-cell-intrinsic mechanisms for this immune upregulation have been largely unexplored. In this study, we show that ASTX660, an antagonist of cIAP1/2 and XIAP, induces expression of immunogenic cell death (ICD) markers in sensitive HNSCC cell lines in vitro. Experiments in syngeneic mouse models of HNSCC showed that ASTX660 can also enhance radiation-induced ICD in vivo. On a functional level, ASTX660 also enhanced killing of multiple murine cell lines by cytotoxic tumor-infiltrating lymphocytes, and when combined with XRT, stimulated clonal expansion of antigen-specific T lymphocytes and expression of MHC class I on the surface of tumor cells. Flow cytometry experiments in several human HNSCC cell lines showed that MHC class I (HLA-A,B,C) was reliably upregulated in response to ASTX660 + TNFα, while increases in other antigen processing machinery (APM) components were variable among different cell lines. These findings suggest that ASTX660 may enhance anti-tumor immunity both by promoting ICD and by enhancing antigen processing and presentation