bluuebunny/crossref_metadata_2025 huggingface dataset:
MIRAGE: a Bayesian rare variant association analysis method incorporating functional information of variants
Authors: Han Shengtong , Sun Xiaotong , Sloofman Laura , Satterstrom F. Kyle , Wang Gao , Liang Lifan , Knoblauch Nicholas , Zhao Siming , Liu Yuwen , Sheng Wenhui , Nguyen Hoang T. , He Xin
Published: November 2019

Many biobanks and consortiums have generated large whole-exome and whole-genome sequencing datasets, making it possible to perform rare variant association studies. Compared to common variants, rare variants tend to have larger effect sizes and generally have much lower linkage disequilibrium (LD), making it easier to identify causal variants. These potential benefits make association analysis with rare variants a priority for human genetics researchers. Because of the low frequencies of these variants, however, the power of single-variant association is often low. To improve the power, numerous methods have been developed to aggregate information of all variants of a gene to better identify risk genes. These gene-based methods, however, often make unrealistic assumptions, e.g. all rare variants in a risk gene have the same effects. In practice, current gene-based analysis methods often fail to show any advantage over simple single-variant analysis. In this work, we develop a Bayesian method: MIxture model based Rare variant Analysis on GEnes (MIRAGE). MIRAGE captures the heterogeneity of variant effects by treating all variants of a gene as a mixture of risk and non-risk variants, and models the prior probabilities of being risk variants as function of external information of variants, such as allele frequencies and predicted deleterious effects. MIRAGE uses an empirical Bayes approach, combining information across genes to estimate these prior probabilities. We demonstrate in both simulations and analysis of an exome-sequencing dataset of Autism, that MIRAGE significantly outperforms current methods for rare variant analysis. The top genes identified by MIRAGE are highly enriched with known or plausible Autism risk genes. Our results highlight several novel Autism genes. MIRAGE is available athttps://xinhe-lab.github.io/mirage.
Bioengineering a novel 3D in-vitro model to recreate physiological oxygen levels and tumor-immune interactions
Authors: Bhattacharya Somshuvra , Calar Kristin , Evans Claire , Petrasko Mark , de la Puente Pilar
Published: November 2019

Oxygen deprivation within tumors is one of the most prevalent causes of resilient cancer cell survival and increased immune evasion in breast cancer (BCa). Current in vitro models do not adequately mimic physiological oxygen levels relevant to breast tissue and its tumor-immune interactions. Here, we propose an approach to engineer a three-dimensional (3D) model (named 3D engineered oxygen, 3D-O) that supports growth of BCa cells and generates physio- and pathophysiological oxygen levels. Low oxygen-induced changes within the 3D-O model supported known tumor hypoxia characteristics such as reduced BCa cell proliferation, increased extracellular matrix protein expression, increased extracellular vesicle secretion and enhanced immune surface marker expression on BCa cells. We further demonstrated that low oxygen-induced changes mimicked tumor-immune interactions leading to immune evasion mechanisms. CD8+ T cell infiltration was significantly impaired under pathophysiological oxygen levels and we were able to establish that hypoxia inhibition re-sensitize BCa cells to cytotoxic CD8+ T cells. Therefore, our novel 3D-O model could serve as a promising platform for the evaluation of immunological events and as a drug-screening platform tool to overcome hypoxia-driven immune evasion.
Gradual replacement of wild bees by honeybees in flowers of the Mediterranean Basin over the last 50 years
Authors: Herrera Carlos M.
Published: November 2019

Evidence for pollinator declines largely originates from mid-latitude regions in North America and Europe. Geographical heterogeneity in pollinator trends combined with geographical biases in pollinator studies, can produce distorted extrapolations and limit understanding of pollinator responses to environmental changes. In contrast to the declines experienced in some well-investigated European and North American regions, honeybees seem to have increased recently in some areas of the Mediterranean Basin. Since honeybees can impact negatively on wild bees, it was hypothesized that a biome-wide alteration in bee pollinator assemblages may be underway in the Mediterranean Basin involving a reduction in the importance of wild bees as pollinators. This hypothesis was tested using published quantitative data on bee pollinators of wild and cultivated plants from studies conducted between 1963-2017 in 13 circum-Mediterranean countries. Honeybee colonies increased exponentially and wild bees were gradually replaced by honeybees in flowers of wild and cultivated plants. Proportion of wild bees at flowers quadruplicated that of honeybees at the beginning of the period, the proportions of both groups becoming roughly similar fifty years later. The Mediterranean Basin is a world biodiversity hotspot for wild bees and wild bee-pollinated plants, and the ubiquitous rise of honeybees to dominance as pollinators could in the long run undermine the diversity of plants and wild bees in the region.
Differential modes of orphan subunit recognition for the WRB/CAML complex
Authors: Inglis Alison J. , Page Katharine R. , Guna Alina , Voorhees Rebecca M.
Published: November 2019

A large proportion of membrane proteins must be assembled into oligomeric complexes for function. How this process occurs is poorly understood, but it is clear that complex assembly must be tightly regulated to avoid accumulation of orphan subunits with potential cytotoxic effects. We interrogated assembly in mammalian cells using a model system of the WRB/CAML complex: an essential insertase for tail-anchored proteins in the endoplasmic reticulum (ER). Our data suggests that the stability of each subunit is differentially regulated. In WRB’s absence, CAML folds incorrectly, causing aberrant exposure of a hydrophobic transmembrane domain to the cytosol. When present, WRB can post-translationally correct the topology of CAML both in vitro and in cells. In contrast, WRB can independently fold correctly, but is still degraded in the absence of CAML. We therefore propose at least two distinct regulatory pathways for the surveillance of orphan subunits during complex assembly in the mammalian ER.
FtsK in motion reveals its mechanism for double-stranded DNA translocation
Authors: Jean Nicolas L. , Rutherford Trevor J. , Löwe Jan
Published: November 2019

FtsK protein contains a fast DNA motor involved in bacterial chromosome dimer resolution. To understand how FtsK moves DNA, we solved the 3.6 Å resolution cryo-EM structure of the motor domain of FtsK while translocating double-stranded DNA. Each subunit of the hexameric ring adopts a unique conformation and one of three nucleotide states. Two DNA-binding loops within four subunits form a pair of spiral staircases within the ring, interacting with the two DNA strands. This suggests that simultaneous conformational changes in all ATPase domains at each catalytic step generate movement through a mechanism related to filament treadmilling. While the ring is only rotating around the DNA slowly, it is instead the conformational states that rotate around the ring as the DNA substrate is pushed through.
Genomic characterization and curation of UCEs improves species tree reconstruction
Authors: Van Dam Matthew H. , Henderson James B. , Esposito Lauren , Trautwein Michelle
Published: November 2019

Ultraconserved genomic elements (UCEs), are generally treated as independent loci in phylogenetic analyses. The identification pipeline for UCE probes is agnostic to genetic identity, only selecting loci that are highly conserved, single copy, without repeats, and of a particular length. Here we characterized UCEs from 12 phylogenomic studies across the animal tree of life, from birds to marine invertebrates. We found that within vertebrate lineages, UCEs are mostly intronic and intergenic, while in invertebrates, the majority are in exons. We then curated 4 different sets of UCE markers by genomic category from 5 different studies including; birds, mammals, fish, Hymenoptera (ants, wasps and bees) and Coleoptera (beetles). Of genes captured by UCEs, we find that many are represented by 2 or more UCEs, corresponding to non-overlapping segments of a single gene. We considered these UCEs to be non-independent, merged all UCEs that belonged to a particular gene, constructed gene and species trees, and then evaluated the subsequent effect of merging co-genic UCEs on gene and species tree reconstruction. Average bootstrap support for merged UCE gene trees were significantly improved across all datasets. Increased loci length appears to drive this increase in bootstrap support. Additionally, we found that gene trees generated from merged UCEs were more accurate than those generated by unmerged and randomly merged UCEs, based on our simulation study. This modest degree of UCE characterization and curation impacts downstream analyses and demonstrates the advantages of incorporating basic genomic characterizations into phylogenomic analyses.
A Plausible Accelerating Function of Intermediate States in Cancer Metastasis
Authors: Goetz Hanah , Melendez-Alvarez Juan R. , Chen Luonan , Tian Xiao-Jun
Published: November 2019

Epithelial-to-mesenchymal transition (EMT) is a fundamental cellular process and plays an essential role in development, tissue regeneration, and cancer metastasis. Interestingly, EMT is not a binary process but instead proceeds with multiple partial intermediate states. However, the functions of these intermediate states are not fully understood. Here, we focus on a general question about how the number of partial EMT states affects cell transformation. First, by fitting a hidden Markov model of EMT with experimental data, we propose a statistical mechanism for EMT in which many unobservable microstates may exist within one of the observable macrostates. Furthermore, we find that increasing the number of intermediate states can accelerate the EMT process and that adding parallel paths or transition layers accelerates the process even further. Last, a stabilized intermediate state traps cells in one partial EMT state. This work advances our understanding of the dynamics and functions of EMT plasticity during cancer metastasis.
Evaluation of haplotype callers for next-generation sequencing of viruses
Authors: Eliseev Anton , Gibson Keylie M. , Avdeyev Pavel , Novik Dmitry , Bendall Matthew L. , Pérez-Losada Marcos , Alexeev Nikita , Crandall Keith A.
Published: November 2019

Currently, the standard practice for assembling next-generation sequencing (NGS) reads of viral genomes is to summarize thousands of individual short reads into a single consensus sequence, thus confounding useful intra-host diversity information for molecular phylodynamic inference. It is hypothesized that a few viral strains may dominate the intra-host genetic diversity with a variety of lower frequency strains comprising the rest of the population. Several software tools currently exist to convert NGS sequence variants into haplotypes. However, previous studies suggest that current approaches of haplotype reconstruction greatly underestimate intra-host diversity. Here, we tested twelve NGS haplotype reconstruction methods using viral populations simulated under realistic evolutionary dynamics. Parameters for the simulated data spanned known fast evolving viruses (e.g., HIV-1) diversity estimates to test the limits of the haplotype reconstruction methods and ensured coverage of predicted intra-host viral diversity levels. Using those parameters, we simulated HIV-1 viral populations of 216-1,185 haplotypes per host at a frequency <7%. All twelve investigated haplotype callers showed variable performance and produced drastically different results that were mainly driven by differences in mutation rate and, to a lesser extent, in effective population size. Most methods were able to accurately reconstruct haplotypes when genetic diversity was low. However, under higher levels of diversity (e.g., those seen intra-host HIV-1 infections), haplotype reconstruction accuracy was highly variable and, on average, poor. High diversity levels led to severe underestimation of, with a few tools greatly overestimating, the true number of haplotypes. PredictHaplo and PEHaplo produced estimates close to the true number of haplotypes, although their haplotype reconstruction accuracy was worse than that of the other ten tools. We conclude that haplotype reconstruction from NGS short reads is unreliable due to high genetic diversity of fast-evolving viruses. Local haplotype reconstruction of longer reads to phase variants may provide a more reliable estimation of viral variants within a population.

Highlights

Haplotype callers for NGS data vary greatly in their performance.

Haplotype callers performance is mainly determined by mutation rate.

Haplotype callers performance is less sensitive to effective population size.

Most haplotype callers perform well with low diversity and poorly with high diversity.

PredictHaplo performs best if genetic diversity is in the range of HIV diversity.
Fbxo45 binds SPRY motifs in the extracellular domain of N-cadherin and regulates neuron migration during brain development
Authors: Na Youn , Calvo-Jiménez Elisa , Kon Elif , Cao Hong , Jossin Yves , Cooper Jonathan A.
Published: November 2019

Several events during normal development of the mammalian neocortex depend on N-cadherin, including the radial migration of immature projection neurons into the cortical plate. Remarkably, radial migration requires the N-cadherin extracellular domain but not N-cadherin-dependent homophilic cell-cell adhesion, suggesting that other N-cadherin-binding proteins may be involved. We used proximity ligation and affinity purification proteomics to identify N-cadherin-binding proteins. Both screens detected MycBP2 and SPRY-domain protein Fbxo45, two components of an intracellular E3 ubiquitin ligase. Fbxo45 appears to be secreted by a non-classical mechanism, not involving a signal peptide and not requiring endoplasmic reticulum to Golgi transport. Fbxo45 binding requires N-cadherin SPRY motifs that are not involved in cell-cell adhesion. SPRY-mutant N-cadherin does not support radial migration in vivo. Radial migration was similarly inhibited when Fbxo45 expression was suppressed. The results suggest that projection neuron migration requires both Fbxo45 and binding of Fbxo45 or another protein to SPRY motifs in the extracellular domain of N-cadherin.
Genetic Analysis of Osteoblast Activity Identifies Zbtb40 as a Regulator of Osteoblast Activity and Bone Mass
Authors: Doolittle Madison L. , Calabrese Gina M , Mesner Larry D. , Godfrey Dana A. , Maynard Robert D. , Ackert-Bicknell Cheryl L. , Farber Charles R.
Published: November 2019

Osteoporosis is a genetic disease characterized by progressive reductions in bone mineral density (BMD) leading to an increased risk of fracture. Over the last decade, genome-wide association studies (GWASs) have identified over 1000 associations for BMD. However, as a phenotype BMD is challenging as bone is a multicellular tissue affected by both local and systemic physiology. Here, we focused on a single component of BMD, osteoblast-mediated bone formation in mice, and identified associations influencing osteoblast activity on mouse Chromosomes (Chrs) 1, 4, and 17. The locus on Chr. 4 was in an intergenic region between Wnt4 and Zbtb40, homologous to a locus for BMD in humans. We tested both Wnt4 and Zbtb40 for a role in osteoblast activity and BMD. Knockdown of Zbtb40, but not Wnt4, in osteoblasts drastically reduced mineralization. Additionally, loss-of-function mouse models for both genes exhibited reduced BMD. Our results highlight that investigating the genetic basis of in vitro osteoblast mineralization can be used to identify genes impacting bone formation and BMD.
DeepACSON: Automated Segmentation of White Matter in 3D Electron Microscopy
Authors: Abdollahzadeh Ali , Belevich Ilya , Jokitalo Eija , Sierra Alejandra , Tohka Jussi
Published: November 2019

Automated segmentation techniques are essential to tracing the entirety of ultrastructures in large three-dimensional electron microscopy (3D-EM) images of the brain tissue. Current automated techniques use deep convolutional neural networks (DCNNs) and rely on high-contrast cellular membranes to trace a small number of neuronal processes in very high-resolution EM datasets. We developed DeepACSON to segment large field-of-view, low-resolution 3D-EM datasets of white matter where tens of thousands of myelinated axons traverse the tissue. DeepACSON performs DCNN-based semantic segmentation and shape decomposition-based instance segmentation. With its top-down design, DeepACSON manages to account for severe membrane discontinuities inescapable with the low-resolution imaging. In particular, the instance segmentation of DeepACSON uses the tubularity of myelinated axons, decomposing an under-segmented myelinated axon into its constituent axons. We applied DeepACSON to ten serial block-face scanning electron microscopy datasets of rats after sham-operation or traumatic brain injury, segmenting hundreds of thousands of long-span myelinated axons, thousands of cell nuclei, and millions of mitochondria with excellent evaluation scores. DeepACSON quantified the morphology and spatial aspects of white matter ultrastructures, capturing nanoscopic morphological alterations five months after the injury.
Illuminance affects epidemiological parameters of banana Yellow Sigatoka in Brazil
Authors: Santana-Filho Djalma M. , da Silva Milene C. , de Souza Jorge T. , Cordeiro Zilton J. M. , Rocha Hermínio S. , Laranjeira Francisco F.
Published: November 2019

The Sigatoka leaf spots are among the most important banana diseases. Although less damaging than black sigatoka, yellow sigatoka (Pseudocercospora musae) still prevails in some regions. This study aimed at testing the hypothesis of light interference in monocyclic parameters of yellow sigatoka epidemics. Grande Naine plantlets kept under contrasting shading conditions had their leaves 1 and 2 inoculated. Evaluations were performed for 60 days. For each inoculated leaf, the time until symptom onset (incubation), presence of infectious lesions (latency), and disease severity (extensive leaf necrosis) according to Stover’s scale modify per Gauhl (1994), called here only Stover’s scale, were registered. Logistic regression was used to assess the relative occurrence risk and survival analysis was used to check the effects of variables on relevant epidemiological parameters. The risks of sporulation and of reaching high severities were lower for plants kept under shading regardless of the acclimation conditions and no effect of leaf age was detected. The logistic regression showed symptoms appearing in both conditions (p=0,85), but have significance difference in occurrence of latent lesions (p=0,013) and necrosis (p<0,0001). The necrosis risk in non-shaded environment arrived 66%. The survival analysis showed significance difference in the time to appear the symptom evaluated in all tested variables (p<0,0001) in function of the cropping system. Lower illuminance negatively affected the incubation, latency and infectious periods, and severity. A shaded system could be tested to produce organic bananas in areas of high risk of occurrence of Yellow sigatoka disease.

Significance and Impact of the Study

Yellow Sigatoka (Pseudocercospora musae) is a banana disease that can cause severe damage if left uncontrolled. Its control is based mostly on fungicides.Our results show that shading downregulates the epidemiological parameters of that disease such as incubation, latent and infectious periods, and symptom’s severity. These results can be the basis for testing alternative cropping systems and producing organic bananas.
5’ splice site GC>GT variants differ from GT>GC variants in terms of their functionality and pathogenicity
Authors: Lin Jin-Huan , Masson Emmanuelle , Boulling Arnaud , Hayden Matthew , Cooper David N. , Férec Claude , Liao Zhuan , Chen Jian-Min
Published: November 2019

In the human genome, most 5’ splice sites (~99%) employ the canonical GT dinucleotide whereas a small minority (~1%) use the non-canonical GC dinucleotide. The functionality and pathogenicity of 5’ splice site GT>GC (i.e., +2T>C) variants have been extensively studied but we still know very little about 5’ splice site GC>GT (+2C>T) variants. Herein, we sought to address this deficiency by performing a meta-analysis of identified +2C>T pathogenic variants together with a functional analysis of +2C>T substitutions using a cell culture-based full-length gene splicing assay. Our results establish a proof of concept that +2C>T variants are qualitatively different from +2T>C variants in terms of their functionality and pathogenicity and suggest that, in sharp contrast with +2T>C variants, most if not all +2C>T variants have no pathological relevance. Our findings have important implications for interpreting the clinical relevance of +2C>T variants but might also improve our understanding of the evolutionary basis of switching between GT and GC 5’ splice sites in mammalian genomes.
The Spectral Sensitivity of the Neurons Mediating Black and White
Authors: Patterson Sara S. , Neitz Maureen , Neitz Jay
Published: November 2019

Our percepts of black and white are not equally strong for all monochromatic lights across the spectrum, but instead have a spectral tuning defined by they ways in which their neural substrates process the outputs of three univariant cone photoreceptors. The neurons mediating black and white and how they combine the cone outputs remain controversial but growing evidence indicates cone-opponent midget ganglion cells are involved. The paradoxical implications of having “chromatic” neurons mediate what is traditionally assumed to be a role of “achromatic” neurons remain unresolved. Here, we investigate whether midget ganglion cells can account for the variation in perceived saturation with wavelength.
Longest protein, longest transcript or most expression, for accurate gene reconstruction of transcriptomes?
Authors: Gilbert Donald G.
Published: November 2019

Methods of transcript assembly and reduction filters are compared for recovery of reference gene sets of human, pig and plant, including longest coding sequence with EvidentialGene, longest transcript with CD-HIT, and most RNA-seq with TransRate. EvidentialGene methods are the most accurate in recovering reference genes, and maintain accuracy for alternate transcripts and paralogs. In comparison, filtering large over-assemblies by longest RNA measures, and most RNA-seq expression measures, discards a large portion of accurate models, especially alternates and paralogs. Accuracy of protein calculations is compared, with errors found in popular methods, as is accuracy of transcript assemblers. Gene reconstruction accuracy depends upon the underlying measurements, where protein criteria, including homology among species, have the strength of evolutionary biology that other criteria lack. EvidentialGene provides a gene reconstruction algorithm that is consistent with genome biology.
Reproduction has different costs for immunity and parasitism in a wild mammal
Authors: Albery Gregory F. , Watt Kathryn A. , Keith Rosie , Morris Sean , Morris Alison , Kenyon Fiona , Nussey Daniel H. , Pemberton Josephine M.
Published: November 2019

Life history theory predicts that reproductive allocation draws resources away from immunity, resulting in increased parasitism. However, studies of reproductive trade‐offs rarely examine multiple measures of reproduction, immunity and parasitism. It is therefore unclear whether the immune costs of reproductive traits correlate with their resource costs, and whether increased parasitism emerges from weaker immunity.

We examined these relationships in wild female red deer (Cervus elaphus) with variable reproductive allocation and longitudinal data on mucosal antibody levels and helminth parasitism. We noninvasively collected faecal samples, counting propagules of strongyle nematodes (order: Strongylida), the common liver fluke Fasciola hepatica and the red deer tissue nematode Elaphostrongylus cervi. We also quantified both total and anti‐strongyle mucosal IgA to measure general and specific immune allocation.

Contrary to our predictions, we found that gestation was associated with decreased total IgA but with no increase in parasitism. Meanwhile, the considerable resource demand of lactation had no further immune cost but was associated with higher counts of strongyle nematodes and E. cervi. These contrasting costs arose despite a negative correlation between antibodies and strongyle count, which implied that IgA was indicative of protective immunity.

Our findings suggest that processes other than classical resource allocation trade‐offs are involved in mediating observed relationships between reproduction, immunity and parasitism in wild mammals. In particular, reproduction–immunity trade‐offs may result from hormonal regulation or maternal antibody transfer, with parasitism increasing as a result of increased exposure arising from resource acquisition constraints. We advocate careful consideration of resource‐independent mechanistic links and measurement of both immunity and parasitism when investigating reproductive costs.

A free Plain Language Summary can be found within the Supporting Information of this article.
S wave attenuation based on Stokes boundary layer
Authors: Li Guangquan
Published: November 2019

Biot theory was based on two ideas: the coupling factor to quantify the kinetic energy of fluid and Darcy permeability to quantify the dissipation function. As Biot theory did not well predict attenuation of ultrasonic S wave, we modify the theory to better characterize the S wave attenuation. The range of the coupling factor is at first estimated in view of fluid mechanics. Application of the original theory to water‐saturated Boise sandstone and brine‐saturated Berea sandstone shows that the model prediction significantly underestimates the S wave attenuation ultrasonically measured. For this reason, we replace Darcy permeability with variable permeability to improve the fluid momentum equation. The new model yields predictions of phase velocity and the quality factor both close to the ultrasonic measurements. The reason why the improved model is superior to Biot theory is that variable permeability is based on the Stokes boundary layer at the fluid–solid interface, thus accurately quantifying the viscous stress between the two phases. Finally, the length scale of the viscous stress is calculated in the mesoscopic sense.
Survival and life table parameters of soybean pod borer Maruca vitrata (Geyer) (Lepidoptera: Crambidae) on leguminous crop cultivars
Authors: Yi Hwijong , Bae Soondo , Jung Jin Kyo , Kim Gil‐Hah , Kim Yonggyun , Yoon Youngnam , Jang Yunwoo , Jung Tae‐Wook , Maharjan Rameswor
Published: November 2019

The soybean pod borer, Maruca vitrata is one of the key insect pests of tropical legumes. It damages tender leaf axils, flower buds, flowers and pods by webbing and boring clusters of flowers and pods. In this study, we investigated the survival and life table parameters of M. vitrata on several leguminous crops; soybean (cvs. Daewon, Poongsannamool and Socheongja), azuki bean (cv. Hongeon), mung bean (cv. Sanpo), and cowpea (cv. Jangchae), compared to artificial diet to assess the antibiosis resistance to M. vitrata. The life‐variables of M. vitrata were significantly affected by the tested legume cultivars. None of the larvae fed cowpea cultivar Jangchae survived. The azuki bean cultivar Hongeon and mung bean cultivar Sanpo were found susceptible to M. vitrata, whereas cowpea cultivar Jangchae and soybean cultivar Daewon showed antibiosis resistance to M. vitrata. Further studies should examine the chemicals associated with leguminous crop cultivars and its mechanism to develop a control method against M. vitrata.
Making sense of environmental sequencing data: Ecologically important functional traits of the protistan groups Cercozoa and Endomyxa (Rhizaria)
Authors: Dumack Kenneth , Fiore‐Donno Anna Maria , Bass David , Bonkowski Michael
Published: November 2019

We have compiled a database of functional traits for two widespread and ecologically important groups of protists, Cercozoa and Endomyxa (Rhizaria). The functional traits of microorganisms are crucially important for interpreting results from environmental sequencing surveys. Linking morphological and ecological traits to environmental factors is common practice in studies involving micro‐ and macroorganisms, but is rarely applied to protists. Our database provides functional and ecologically significant traits linked to morphology, nutrition, locomotion and habitats. We discuss how the use of functional traits may help to unveil underlying ecosystem processes. This database is intended as a common reference for the molecular ecology community and will boost the understanding of ecosystem functions, especially those driven by biological interactions.
A probabilistic model for designing and assessing the performance of eDNA sampling protocols
Authors: Song Jeffery W. , Schultz Martin T. , Casman Elizabeth A. , Bockrath Katherine D. , Mize Erica , Monroe Emy M. , Tuttle‐Lau Maren , Small Mitchell J.
Published: November 2019

Environmental DNA (eDNA) sampling, the detection of species‐specific genetic material in water samples, is an emerging tool for monitoring aquatic invasive species. Optimizing eDNA sampling protocols can be challenging because there is imperfect understanding of how each step of the protocol influences its sensitivity. This paper develops a probabilistic model that characterizes each step of an eDNA sampling protocol to evaluate the protocol's overall detection sensitivity for one sample. The model is then applied to analyse how changes over time made to the eDNA sampling protocol to detect bighead (BH) and silver carp (SC) eDNA have influenced its sensitivity, and hence interpretation of the results. The model shows that changes to the protocol have caused the sensitivity of the protocol to fluctuate. A more efficient extraction method in 2013, new species‐specific markers with a qPCR assay in 2014, and a more efficient capture method in 2015 have improved the sensitivity, while switching to a larger elution volume in 2013 and a smaller sample volume in 2015 have reduced the sensitivity. Overall, the sensitivity of the current protocol is higher for BH eDNA detection and SC eDNA detection compared to the original protocol used from 2009 to 2012. The paper shows how this model of eDNA sampling can be used to evaluate the effect of proposed changes in an eDNA sampling and analysis protocol on the sensitivity of that protocol to help researchers optimize their design.
Using stable isotope analysis to answer fundamental questions in invasion ecology: Progress and prospects
Authors: McCue Marshall D. , Javal Marion , Clusella‐Trullas Susana , Le Roux Johannes J. , Jackson Michelle C. , Ellis Allan G. , Richardson David M. , Valentine Alex J. , Terblanche John S.
Published: November 2019

What makes some species successful invaders while others fail, and why some invaders have major impacts in invaded ecosystems are pivotal questions that are attracting major research effort. The increasing availability of high resolution, georeferenced stable isotope landscapes (‘isoscapes’), coupled with the commercialization of stable isotope‐enriched tracer molecules and the development of new analytical approaches, is facilitating novel applications of stable isotope techniques in ecology. We can now address ecological questions that were previously intractable.

We review and discuss how stable isotope analysis (SIA) can complement fundamental research themes in the study of biological invasions, especially in answering questions relating to the physiological and ecological mechanisms underlying invasion processes and invader impacts.

SIA was first used for simply describing the diet of invaders but, more recently, SIA‐informed metrics of population and community trophic structure have been advanced. These approaches now permit the comparison of diets across space and time and provide quantitative tools to compare food webs across different stages of invasion.

SIA has also been pivotal in quantifying competition for resources between native and non‐native species (e.g. competition for food, water, or nutrient use). Specific questions related to modes of dispersal (e.g. origin and distance/direction travelled) and mechanisms of establishment can also be addressed using SIA in diverse taxa.

An overarching goal is to highlight examples of recent studies that have used SIA in key areas of invasion ecology and use these to synthesize testable predictions where SIA could be applied to future studies. We conclude by highlighting several paths forward and describing how unresolved challenges in quantifying the rates, impacts, and mechanisms underlying invasions could potentially benefit from the use of SIA.
Polypharmacy at discharge in older hospitalised patients in Vietnam and its association with frailty
Authors: Nguyen Thanh Xuan , Nguyen Tu N. , Nguyen Anh Trung , Nguyen Huong Thi Thu , Nguyen Thu Thi Hoai , Nguyen Tam Ngoc , Pham Thang , Vu Huyen Thi Thanh
Published: November 2019

Objectives

To investigate the prevalence of polypharmacy and the common drugs prescribed at discharge in frail and non‐frail older inpatients, and to examine whether frailty is significantly associated with polypharmacy.

Methods

Cross‐sectional analysis from data of a study about the prevalence of frailty in older inpatients in Vietnam in 2015. Polypharmacy was defined as using ≥5 medications. Frailty was defined by Fried's frailty criteria.

Results

There were 382 participants, mean age 76.4, 56.5% female and 35.9% frail. At discharge, 59.2% had polypharmacy (62.8% in the frail and 57.1% in the non‐frail). Vitamin/supplements were the most common drugs prescribed, followed by antiplatelets. Frailty was not significantly associated with polypharmacy (adjusted OR 1.45, 95% CI 0.89‐2.34).

Conclusions

The prevalence of polypharmacy at discharge was high in both frail and non‐frail participants. The association between frailty and polypharmacy needs to be investigated further in multicentre studies with larger sample sizes in Vietnam.
The association between family history of diabetes mellitus and offspring long‐term neurological hospitalisation
Authors: Moscovici Khen , Wainstock Tamar , Sheiner Eyal , Pariente Gali
Published: November 2019

Aim

The aim of the present study was to determine whether being born to non‐diabetic mother with a family history of diabetes mellitus (DM) is associated with higher rates of long‐term neurological hospitalisations of the offspring.

Methods

A retrospective analysis of all live births and paediatric hospitalisations at Soroka University Medical Center between 1991 and 2014 was performed. Family history of DM was collected from prepartum women using anamnesis. During the study period, 208 728 deliveries met the inclusion criteria, and of them 8.2% (n = 17 040) were of non‐diabetic mothers with family history of DM. Rates of neurological hospitalisation with or without family history were analysed.

Results

Offspring born to non‐diabetic mothers with family history of DM had higher rates of neurological hospitalisations. The cumulative incidence of long‐term neurological hospitalisations was higher as compared with those without family history of DM (log‐rank test P = .007). Neurological hospitalisations was higher by 13% in the study group, after controlling for confounders such as maternal age, maternal obesity, hypertensive disorders, birth weight and caesarean delivery. (adjusted odds ratio 1.13, 95% confidence interval 1.04‐1.23).

Conclusion

Being born to a non‐diabetic mother with a family history of DM is independently associated with higher long‐term neurological hospitalisations of the offspring.
A family‐oriented intervention programme to curtail obesity from five years of age had no effect over no intervention
Authors: Donkor Hilde Mjell , Grundt Jacob Holter , Júlíusson Petur Benedikt , Eide Geir Egil , Hurum Jørgen , Bjerknes Robert , Markestad Trond
Published: November 2019

Aim

To examine the effect of a family‐oriented multidisciplinary intervention programme to curtail weight increase in young children with obesity.

Methods

Children who weighed more than one kilogram above the 97th percentile for height at the preschool assessment in Oppland County, Norway, were identified. Parents residing in one part of the county were invited to participate in a group‐based three‐year intervention programme while the rest had no interventions. Body mass index (BMI) and family characteristics at entry and measurements at birth were explanatory variables, and change in BMI standard deviation score (SDS) the outcome measure. For the intervention group, outcome was also related to skinfold thicknesses, waist‐to‐height ratio and physical ability.

Results

The programme was completed by 31 families in the intervention and 33 in the control group. At entry, the respective median (interquartile) age was 5.83 (0.36) and 5.74 (0.66) years, and the BMI SDS 2.35 (1.06) and 1.95 (0.49), P = .012. The median decrease in BMI SDS was 0.19 in both groups. The decline increased with increasing BMI SDS at entry, but irrespective of group. Social or behavioural factor or other anthropometric measures were not associated with outcome.

Conclusion

The intervention programme had no effect on BMI SDS.
Heat‐related changes in skin tissue dielectric constant (TDC)
Authors: Mayrovitz Harvey N. , Berdichevskiy Garry , Lorenzo‐Valido Cindy , Clavijo Fernandez Marcos
Published: November 2019

The impact of 20 min of whole‐body heating (WBH) on the tissue dielectric constant (TDC) of forearm and hand skin was evaluated in 24 young adults. TDC was measured in triplicate at 300 MHz using an open‐ended transmission line method in which the effective measurement depth was about 2 mm. TDC measurements are an effective way to assess and track localized oedema and lymphoedema. The underlying hypothesis was that heat‐induced eccrine gland activation would increase TDC values via an increase in fluid within the TDC measurement volume. The goal was to test this concept and to determine the magnitude of the change when environmental temperatures were elevated to near 42°C and to estimate TDC recovery time. The practical aspect of this research is motivated by the fact that patients in whom such measurements are made may arrive at the clinic in various states of sweat gland activation. Thus, knowledge of the effect of such activation on measured TDC values permits better understanding of possible relationships between such activation and TDC values. Results showed that increasing environmental temperature from 23·3 ± 1·6 to 41·5 ± 1·3°C increased forearm and thenar eminence skin temperatures to 37·8 ± 0·5 and 37·9 ± 0·4°C, respectively. These changes were associated with increases in TDC at arm from 30·7 ± 4·6 to 36·3 ± 5·7 (18·2%) and at hand from 34·7 ± 4·9 to 45·1 ± 5·5 (30%). Based on calculated TDC recovery rates, it is concluded that temperature‐related TDC variability can be minimized using a wait time of at least 15 min after bandage removal prior to TDC measurements in affected limbs.
Ipilimumab/nivolumab‐induced pseudolymphoma in a patient with malignant melanoma
Authors: Ayoubi Noura , Haque Adel , Vera Nora , Ma Sophia , Messina Jane , Khushalani Nikhil , Seminario‐Vidal Lucia
Published: November 2019

Combination therapy with ipilimumab and nivolumab is an adjuvant treatment approach for metastatic melanoma that boasts increased 3‐year survival when compared with a single immunotherapy agent. Combination therapy, however, is associated with increased toxicities, especially cutaneous side‐effects. Here we present a patient with metastatic melanoma and a sudden eruption of painful nodules on the face and arms 10 days after the administration of the fourth dose of combination ipilimumab/nivolumab. Biopsies demonstrated lymphoid hyperplasia, not clinically or pathologically consistent with an infectious, malignant or autoimmune etiology; a diagnosis of pseudolymphoma secondary to ipilimumab/nivolumab was made. After a steroid taper, the lesions resolved, and the patient was restarted on nivolumab monotherapy 2 weeks later without recurrence of symptoms or disease.
Social accountability in metropolitan cities: Strategies and legacies in Delhi and São Paulo
Authors: Houtzager Peter P. , Acharya Arnab K. , Amancio Julia , Chowdhury Aheli , Dowbor Monika , Pande Suchi
Published: November 2019

Motivation

Social accountability by civil society is an important part of strengthening democratic governance and improving the delivery of public services.

Purpose

The article documents the landscape of social accountability in two metropolitan cities. We identify widespread and contrasting forms of activism by the poor in metropolitan Delhi and São Paulo to improve public services, and a mix of factors that allow and impel the poor to engage in social accountability. While impact evaluation studies have identified accountability tools that can, in certain contexts, help improve public services, and case studies have explored accountability campaigns, neither has sought to examine and explain how widespread activism is, its intensity and which strategies are commonly used.

Approach and methods

The study is built on an unusual set of nested comparisons and survey method, comparing accountability activism in Delhi and São Paulo, services in healthcare and social assistance, and 40 low‐income micro‐regions of each city. We leverage these comparisons to identify causal factors that produce the patterns of activism we find. We conducted a survey of civil society leaders in each of these micro‐regions.

Findings

We find that accountability activism is high on the civil society agenda—it is common in almost all low‐income regions of Delhi and São Paulo. Its intensity and strategies vary in unexpected ways across the cities and services, suggesting that no single set of factors can explain all three features of activism. The type of service, presence of translocal actors, and institutions that seek to give citizens greater access to, and control over, government all shape different aspects of accountability activism. Going further along the causal chain, we argue that differences in the presence of translocal actors and institutional context are the legacy of earlier cycles of civil society mobilization.

Policy implications

Initiatives to introduce or support social accountability, and research on the topic, need to take account of the various causes of different aspects of accountability, and to take into account the historical formation of the landscape of activism in which they work.
A field cage study of the optimal age for release of radio‐sterilized Aedes albopictus mosquitoes in a sterile insect technique program
Authors: Iyaloo Diana Pillay , Oliva Clelia , Facknath Sunita , Bheecarry Ambicadutt
Published: November 2019

The use of the sterile insect technique (SIT) is being considered as an additional tool for the control of Aedes albopictus (Skuse) (Diptera: Culicidae), the vector of Chikungunya and Dengue viruses in Mauritius. The aim of this study was to assess the competitiveness value of sterile males of different age and under various release conditions. Three release ratios were tested with sterile males of either 1, 3, or 5 days old at release. The competition of sterile males against same age or a mixed age population of fertile males (which is more representative of the field situation) was also investigated. The participation in mating (observed through single female oviposition), the average‐induced sterility, and the male competitiveness index indicated that 3‐day‐old sterile males have the best balance between survival and mating capacity, and should therefore be the favored age of release in the field. Reduction in the cage fertility was obtained at 5‐to‐1 release ratio; however, it is speculated that at least a 10‐fold ratio of sterile‐to‐fertile males should be chosen to induce substantial sterility in the wild Ae. albopictus population in the SIT pilot release site in Mauritius. Interestingly, this study showed for the first time that the age of the fertile male population against which the sterile males compete is a very important parameter that can significantly affect the sexual performance of sterile males, leading to overestimation of their competitiveness values.
Secreted Frizzled‐related proteins (sFRPs) in osteo‐articular diseases: much more than simple antagonists of Wnt signaling?
Authors: Claudel Marion , Jouzeau Jean‐Yves , Cailotto Frédéric
Published: November 2019

Osteo‐articular diseases are characterized by a dysregulation of joint and/or bone homeostasis. These include diseases affecting the joints originally, such as osteoarthritis and rheumatoid arthritis, or the bone, such as osteoporosis. Inflammation and the involvement of Wingless‐related integration site (Wnt) signaling pathways are key pathophysiological features of these diseases resulting in tissue degradation by matrix‐degrading enzymes, namely matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTs), secreted by the joint resident cells and/or by infiltrating immune cells. Activation of Wnt signaling pathways is modulated by different families of proteins, including Dickkopfs and the secreted Frizzled‐related proteins (sFRPs). The sFRP family is composed of five secreted glycoproteins in mammals that regulate Wnt signaling in the extracellular compartment. Indeed, sFRPs are able to bind both to the soluble Wnt ligands and to their cell membrane receptors, the Frizzled proteins. Their expression profile is altered in osteo‐articular diseases, suggesting that they could account for the abnormal activation of Wnt pathways. In the present article, we review how sFRPs are more than simple antagonists of the Wnt signaling pathways and discuss their pathophysiological relevance in the context of osteo‐articular diseases. We detail their Wnt‐dependent and their Wnt‐independent roles, with a particular emphasis on their ability to modulate the inflammatory response and extracellular matrix (ECM) remodeling. We also discuss their potential therapeutic use with a focus on bone remodeling, osteo‐articular cancers, and tissue engineering.
Can online annual general meetings increase shareholders’ participation in corporate governance?
Authors: Gao Huasheng , Huang Jun , Zhang Tianshu
Published: November 2019

We find that annual shareholder meetings conducted online can significantly increase the participation of shareholders, especially minority shareholders. This finding is more evident when the cost of physically attending the annual meeting is higher and when the firm's ownership is more dispersed. We further document significant positive stock returns when firms initiate annual online meetings. We also find that such online meetings help improve corporate governance. Overall, we provide evidence that online shareholder meetings provide shareholders a cost‐effective way to participate in governance issues.