The Obesity-Associated Polymorphisms FTO rs9939609 and MC4R rs17782313 and Endometrial Cancer Risk in Non-Hispanic White Women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR)  = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis

Evaluation of cell-based and surrogate SARS-CoV-2 neutralization assays

Determinants of protective immunity against SARS-CoV-2 infection require the development of well-standardized, reproducible antibody assays. This need has led to the emergence of a variety of neutralization assays. Head-to-head evaluation of different SARS-CoV-2 neutralization platforms could facilitate comparisons across studies and laboratories. Five neutralization assays were compared using forty plasma samples from convalescent individuals with mild-to-moderate COVID-19: four cell-based systems using either live recombinant SARS-CoV-2 or pseudotyped viral particles created with lentivirus (LV) or vesicular stomatitis virus (VSV) packaging and one surrogate ELISA-based test that measures inhibition of the spike protein receptor binding domain (RBD) binding its receptor, human angiotensin converting enzyme 2 (hACE2). Vero, Vero E6, HEK293T expressing hACE2, and TZM-bl cells expressing hACE2 and transmembrane serine protease 2 were tested. All cell-based assays showed 50% neutralizing dilution (ND50) geometric mean titers (GMTs) that were highly correlated (Pearson r = 0.81–0.89) and ranged within 3.4-fold. The live-virus assay and LV-pseudovirus assays with HEK293T/hACE2 cells showed very similar mean titers: 141 and 178, respectively. ND50 titers positively correlated with plasma IgG targeting SARS-CoV-2 spike and RBD (r = 0.63–0.89), but moderately correlated with nucleoprotein IgG (r = 0.46–0.73). ND80 GMTs mirrored ND50 data and showed similar correlation between assays and with IgG concentrations. The VSV-pseudovirus assay and LV-pseudovirus assay with HEK293T/hACE2 cells in low and high-throughput versions were calibrated against the WHO SARS-CoV-2 IgG standard. High concordance between the outcomes of cell-based assays with live and pseudotyped virions enables valid cross-study comparison using these platforms. 24

Maximizing biodiversity co-benefits under REDD+: a decoupled approach

Current debates on biodiversity co-benefits under REDD+ are marked by considerable ambiguity and contention. Nevertheless, REDD+ continues to represent one of the most important opportunities for global biodiversity conservation, and the question of how best to achieve biodiversity co-benefits remains an important one. Thus far, most biodiversity conservation in the context of REDD+ is predicated on the notion that services are co-located on a landscape. In contrast, this letter argues that decoupling biodiversity and carbon services on a landscape through national-level planning is a better approach to biodiversity conservation under REDD+. We discuss the fundamental ecological differences between the two services and use principles of resource economics to demonstrate that a decoupled approach will be more efficient, more flexible, and better able to mobilize sufficient finance for biodiversity conservation than a coupled approach

Environmental and geographic factors driving dung beetle (Coleoptera: Scarabaeidae: Scarabaeinae) diversity in the dipterocarp forests of Peninsular Malaysia

Doll, Hannah M., Butod, Elizabeth, Harrison, Rhett D., Fletcher, Christine, Kassim, Abd Rahman, Ibrahim, Shamsudin, Potts, Matthew D. (2014): Environmental and geographic factors driving dung beetle (Coleoptera: Scarabaeidae: Scarabaeinae) diversity in the dipterocarp forests of Peninsular Malaysia. Raffles Bulletin of Zoology 62: 549-560, DOI: http://doi.org/10.5281/zenodo.535447

Utilizing novel diversity estimators to quantify multiple dimensions of microbial biodiversity across domains

Abstract Background Microbial ecologists often employ methods from classical community ecology to analyze microbial community diversity. However, these methods have limitations because microbial communities differ from macro-organismal communities in key ways. This study sought to quantify microbial diversity using methods that are better suited for data spanning multiple domains of life and dimensions of diversity. Diversity profiles are one novel, promising way to analyze microbial datasets. Diversity profiles encompass many other indices, provide effective numbers of diversity (mathematical generalizations of previous indices that better convey the magnitude of differences in diversity), and can incorporate taxa similarity information. To explore whether these profiles change interpretations of microbial datasets, diversity profiles were calculated for four microbial datasets from different environments spanning all domains of life as well as viruses. Both similarity-based profiles that incorporated phylogenetic relatedness and naïve (not similarity-based) profiles were calculated. Simulated datasets were used to examine the robustness of diversity profiles to varying phylogenetic topology and community composition. Results Diversity profiles provided insights into microbial datasets that were not detectable with classical univariate diversity metrics. For all datasets analyzed, there were key distinctions between calculations that incorporated phylogenetic diversity as a measure of taxa similarity and naïve calculations. The profiles also provided information about the effects of rare species on diversity calculations. Additionally, diversity profiles were used to examine thousands of simulated microbial communities, showing that similarity-based and naïve diversity profiles only agreed approximately 50% of the time in their classification of which sample was most diverse. This is a strong argument for incorporating similarity information and calculating diversity with a range of emphases on rare and abundant species when quantifying microbial community diversity. Conclusions For many datasets, diversity profiles provided a different view of microbial community diversity compared to analyses that did not take into account taxa similarity information, effective diversity, or multiple diversity metrics. These findings are a valuable contribution to data analysis methodology in microbial ecology

The adaptor protein 2 (AP2) complex modulates habituation and behavioral selection across multiple pathways and time windows

Summary: Animals constantly integrate sensory information with prior experience to select behavioral responses appropriate to the current situation. Genetic factors supporting this behavioral flexibility are often disrupted in neuropsychiatric conditions, such as the autism-linked ap2s1 gene which supports acoustically evoked habituation learning. ap2s1 encodes an AP2 endocytosis adaptor complex subunit, although its behavioral mechanisms and importance have been unclear. Here, we show that multiple AP2 subunits regulate acoustically evoked behavior selection and habituation learning in zebrafish. Furthermore, ap2s1 biases escape behavior choice in sensory modality-specific manners, and broadly regulates action selection across sensory contexts. We demonstrate that the AP2 complex functions acutely in the nervous system to modulate acoustically evoked habituation, suggesting several spatially and/or temporally distinct mechanisms through which AP2 regulates escape behavior selection and performance. Altogether, we show the AP2 complex coordinates action selection across diverse contexts, providing a vertebrate model for ap2s1’s role in human conditions including autism spectrum disorder