bluuebunny/crossref_metadata_2025 huggingface dataset:
General-term rigidity is meaning constancy
Authors: Haraldsen Fredrik
Published: February 2021

It is often thought that some general terms or kind terms, in particular natural kind terms, are rigid designators, and that a properly extended notion of singular-term rigidity can help explain the behaviour of such general terms. In this article, I argue that the only legitimate notion of general-term rigidity is a trivial one and identify some crucial asymmetries between a posteriori necessary truths involving names and a posteriori necessary truths involving general terms. If we pay attention to these asymmetries, it becomes clear that attempts to draw a non-trivial rigid/non-rigid distinction for general terms are bound to fail to offer the explanations we expected. As opposed to singular terms, what is interesting about the behaviour of natural kind terms, even in modal contexts, cannot be accounted for by modal distinctions like rigidity/non-rigidity but must rather track non-modal features.
Changes in plant collection practices from the 16th to 21st centuries: implications for the use of herbarium specimens in global change research
Authors: Kozlov Mikhail V , Sokolova Irina V , Zverev Vitali , Zvereva Elena L
Published: February 2021

Background and Aims

Herbaria were recently advertised as reliable sources of information regarding historical changes in plant traits and biotic interactions. To justify the use of herbaria in global change research, we asked whether the characteristics of herbarium specimens have changed during the past centuries and whether these changes were due to shifts in plant collection practices.

Methods

We measured nine characteristics from 515 herbarium specimens of common European trees and large shrubs collected from 1558 to 2016. We asked botanists to rank these specimens by their scientific quality, and asked artists to rank these specimens by their beauty.

Key Results

Eight of 11 assessed characteristics of herbarium specimens changed significantly during the study period. The average number of leaves in plant specimens increased 3-fold, whereas the quality of specimen preparation decreased. Leaf size negatively correlated with leaf number in specimens in both among-species and within-species analyses. The proportion of herbarium sheets containing plant reproductive structures peaked in the 1850s. The scientific value of herbarium specimens increased until the 1700s, but then did not change, whereas their aesthetic value showed no systematic trends.

Conclusions

Our findings strongly support the hypothesis that many characteristics of herbarium specimens have changed systematically and substantially from the 16th to 21st centuries due to changes in plant collection and preservation practices. These changes may both create patterns which could be erroneously attributed to environmental changes and obscure historical trends in plant traits. The utmost care ought to be taken to guard against the possibility of misinterpretation of data obtained from herbarium specimens. We recommend that directional changes in characters of herbarium specimens which occurred during the past 150‒200 years, primarily in specimen size and in the presence of reproductive structures, are accounted for when searching for the effects of past environmental changes on plant traits.
A novel method for data fusion over entity-relation graphs and its application to protein–protein interaction prediction
Authors: Raimondi Daniele , Simm Jaak , Arany Adam , Moreau Yves
Published: February 2021

Motivation

Modern bioinformatics is facing increasingly complex problems to solve, and we are indeed rapidly approaching an era in which the ability to seamlessly integrate heterogeneous sources of information will be crucial for the scientific progress. Here, we present a novel non-linear data fusion framework that generalizes the conventional matrix factorization paradigm allowing inference over arbitrary entity-relation graphs, and we applied it to the prediction of protein–protein interactions (PPIs). Improving our knowledge of PPI networks at the proteome scale is indeed crucial to understand protein function, physiological and disease states and cell life in general.

Results

We devised three data fusion-based models for the proteome-level prediction of PPIs, and we show that our method outperforms state of the art approaches on common benchmarks. Moreover, we investigate its predictions on newly published PPIs, showing that this new data has a clear shift in its underlying distributions and we thus train and test our models on this extended dataset.

Supplementary information

Supplementary data are available at Bioinformatics online.
PhyKIT: a broadly applicable UNIX shell toolkit for processing and analyzing phylogenomic data
Authors: Steenwyk Jacob L , Buida Thomas J , Labella Abigail L , Li Yuanning , Shen Xing-Xing , Rokas Antonis
Published: February 2021

Motivation

Diverse disciplines in biology process and analyze multiple sequence alignments (MSAs) and phylogenetic trees to evaluate their information content, infer evolutionary events and processes and predict gene function. However, automated processing of MSAs and trees remains a challenge due to the lack of a unified toolkit. To fill this gap, we introduce PhyKIT, a toolkit for the UNIX shell environment with 30 functions that process MSAs and trees, including but not limited to estimation of mutation rate, evaluation of sequence composition biases, calculation of the degree of violation of a molecular clock and collapsing bipartitions (internal branches) with low support.

Results

To demonstrate the utility of PhyKIT, we detail three use cases: (1) summarizing information content in MSAs and phylogenetic trees for diagnosing potential biases in sequence or tree data; (2) evaluating gene–gene covariation of evolutionary rates to identify functional relationships, including novel ones, among genes and (3) identify lack of resolution events or polytomies in phylogenetic trees, which are suggestive of rapid radiation events or lack of data. We anticipate PhyKIT will be useful for processing, examining and deriving biological meaning from increasingly large phylogenomic datasets.

Availability and implementation

PhyKIT is freely available on GitHub (https://github.com/JLSteenwyk/PhyKIT), PyPi (https://pypi.org/project/phykit/) and the Anaconda Cloud (https://anaconda.org/JLSteenwyk/phykit) under the MIT license with extensive documentation and user tutorials (https://jlsteenwyk.com/PhyKIT).

Supplementary information

Supplementary data are available at Bioinformatics online.
Single well, single-common primer pair, dual probe, duplex qPCR assay for the quantification of mRNA splicing variants
Authors: Wang Janice , Wong Winifred P , Link Emma O , Olivares Shantel , Adelman Cade T , Henkel Anne S , El Muayed Malek
Published: February 2021

Quantifying the ratio of alternatively spliced mRNA variants of genes with known alternative splicing variants is highly relevant for many applications. Herein, we describe the validation of a quantitative PCR design for the simplified quantification of known mRNA splice variants. The assay uses a single-common primer pair, dual probe design for the determination of splicing variants in a single well configuration. We used murine XBP-1 splicing variants, XBP-1S and XBP-1U, to validate and demonstrate the performance characteristics of this approach. Using synthetic XBP-1S and XBP-1U cDNA as well as cDNA synthesized from mouse beta-cell line MIN6, we established the performance parameters and dynamic range of the assay. Reliable quantification of both variants at varying concentration gradients was shown. No cross detection of XBP-1U by the XBP-1S probe was detected and only marginal XBP-1S cross detection by the XBP-1U probe was detected at high concentration gradients that are unlikely to be relevant. We demonstrated that the assay accurately detected changes of XBP-1 splice variants in mouse liver subjected to pharmacologically induced ER stress without the need for normalization to a reference gene.
Unravelling theHabenaria repens(Orchidaceae) complex in Brazil: a biosystematic and molecular phylogenetic approach
Authors: Lau Bruna Ladeira , Batista João Aguiar Nogueira , Massensini Junior Antônio , Whitten W Mark , Borba Eduardo Leite
Published: February 2021

Habenaria repens (Orchidaceae) represents a species complex distributed from the southern USA to northern Argentina, including several morphological variants, here referred to as morphotypes. To investigate and clarify the morphological and genetic relationships between these morphotypes and resolve the taxonomy of the complex, we applied a biosystematic multi-population approach using molecular phylogenetic, morphometric and population genetics analyses in the group. We sampled 31 (phylogenetic analyses) and 20 (morphometric and microsatellite analyses) populations of Habenaria aranifera and H. repens from Brazil and the USA, including six morphotypes of H. repens. Bayesian and maximum parsimony phylogenetic analyses of nuclear ribosomal (ITS and ETS) and plastid (matK, trnK and rps16-trnK) markers revealed that the complex is polyphyletic, subdivided into three distantly related clades. Population genetic analyses using microsatellites showed a remarkably similar structure to the phylogenetic analyses, but both were different from the morphometric analyses of floral characters, indicating cases of diversification and convergence, probably due to pollination processes. Habenaria aranifera is embedded in a paraphyletic and polymorphic H. repens with a broad geographical distribution and other attributes of an ochlospecies, probably constituting a progenitor–derivative pair. Our results support the recognition of H. aranifera, H. repens and three or four new species.
Medial septal GABAergic neurons reduce seizure duration upon optogenetic closed-loop stimulation
Authors: Hristova Katerina , Martinez-Gonzalez Cristina , Watson Thomas C , Codadu Neela K , Hashemi Kevan , Kind Peter C , Nolan Matthew F , Gonzalez-Sulser Alfredo
Published: February 2021

Seizures can emerge from multiple or large foci in temporal lobe epilepsy, complicating focally targeted strategies such as surgical resection or the modulation of the activity of specific hippocampal neuronal populations through genetic or optogenetic techniques. Here, we evaluate a strategy in which optogenetic activation of medial septal GABAergic neurons, which provide extensive projections throughout the hippocampus, is used to control seizures. We utilized the chronic intrahippocampal kainate mouse model of temporal lobe epilepsy, which results in spontaneous seizures and as is often the case in human patients, presents with hippocampal sclerosis. Medial septal GABAergic neuron populations were immunohistochemically labelled and were not reduced in epileptic conditions. Genetic labelling with mRuby of medial septal GABAergic neuron synaptic puncta and imaging across the rostral to caudal extent of the hippocampus, also indicated an unchanged number of putative synapses in epilepsy. Furthermore, optogenetic stimulation of medial septal GABAergic neurons consistently modulated oscillations across multiple hippocampal locations in control and epileptic conditions. Finally, wireless optogenetic stimulation of medial septal GABAergic neurons, upon electrographic detection of spontaneous hippocampal seizures, resulted in reduced seizure durations. We propose medial septal GABAergic neurons as a novel target for optogenetic control of seizures in temporal lobe epilepsy.
Preparative Isolation and Purification of Calycosin and Formononetin from Astragali Radix using Hydrolytic Extraction Combined with High Speed Countercurrent Chromatography
Authors: Pan Conglei , Wang Hao , Shan Hu , Lü Haitao
Published: February 2021

Calycosin and formononetin were efficiently extracted from Astragali Radix and purified by high-speed countercurrent chromatography. Calycosin and formononetin could be hydrolyzed from calycosin-7-glucoside and ononin, respectively. The best extraction conditions were realized by single factor and orthogonal experiments, which were 100% ethanol, 2.5 mol/L hydrochloric acid, 1:40 ratio of solid to liquid, extracted 2 h and one time. The two-phase solvent system of n-hexane-ethyl acetate-ethanol-water (3:5:3:5, v/v) was selected for the purification of calycosin, and 1.3 mg calycosin (the purity was 95.8% and the recovery was 85.9%) was obtained from 264.9-mg crude extraction. The two-phase solvent system of n-hexane-ethyl acetate-ethanol-water (4:5:4:5, v/v) was selected for the purification of formononetin, and 2.0 mg formononetin (the purity was 98.9% and the recovery was 84.4%) was obtained from 248.9-mg crude extraction. Their structures were identified by HPLC, melting points, UV, FTIR, ESI-MS, 1H NMR and 13C NMR spectrum. According to the antioxidant activity assay, the scavenging abilities of calycosin to 1,1-diphenyl-2-picrylhydrazyl and hydroxyl free radicals (·OH) were stronger. The scavenging effect of formononetin was not demonstrated.
Aspergillus Polymerase Chain Reaction—An Update on Technical Recommendations, Clinical Applications, and Justification for Inclusion in the Second Revision of the EORTC/MSGERC Definitions of Invasive Fungal Disease
Authors: White P Lewis , Bretagne Stephane , Caliendo Angela M , Loeffler Juergen , Patterson Thomas F , Slavin Monica , Wingard John R
Published: February 2021

Aspergillus polymerase chain reaction testing of blood and respiratory samples has recently been included in the second revision of the EORTC/MSGERC definitions for classifying invasive fungal disease. This is a result of considerable efforts to standardize methodology, the availability of commercial assays and external quality control programs, and additional clinical validation. This supporting article provides both clinical and technical justifications for its inclusion while also summarizing recent advances and likely future developments in the molecular diagnosis of invasive aspergillosis.
Assessment of the Role of 1,3-β-d-Glucan Testing for the Diagnosis of Invasive Fungal Infections in Adults
Authors: Lamoth F , Akan H , Andes D , Cruciani M , Marchetti O , Ostrosky-Zeichner L , Racil Z , Clancy C J
Published: February 2021

Detection of 1,3-β-d-glucan (BDG) in serum has been evaluated for its inclusion as a mycological criterion of invasive fungal infections (IFI) according to EORTC and Mycoses Study Group (MSG) definitions. BDG testing may be useful for the diagnosis of both invasive aspergillosis and invasive candidiasis, when interpreted in conjunction with other clinical/radiological signs and microbiological markers of IFI. However, its performance and utility vary according to patient population (hematologic cancer patients, solid-organ transplant recipients, intensive care unit patients) and pretest likelihood of IFI. The objectives of this article are to provide a systematic review of the performance of BDG testing and to assess recommendations for its use and interpretation in different clinical settings.
Understanding metrics of stress in the context of invasion history: the case of the brown treesnake (Boiga irregularis)
Authors: Claunch Natalie , Moore Ignacio , Waye Heather , Schoenle Laura , Oakey Samantha J , Reed Robert N , Romagosa Christina
Published: February 2021

Invasive species can exert rapid depletion of resources after introduction and, in turn, affect their own population density. Additionally, management actions can have direct and indirect effects on demography. Physiological variables can predict demographic change but are often restricted to snapshots-in-time and delayed confirmation of changes in population density reduces their utility. To evaluate the relationships between physiology and demography, we assessed metrics of individual and demographic stress (baseline and 1-h corticosterone (CORT), body condition and bacterial killing ability) in the invasive snake Boiga irregularis on Guam collected in intervals of 10–15 years. We also assessed potential discrepancies between different methods of measuring hormones [radioimmunoassay (RIA) versus enzyme immunoassay (EIA)]. The magnitude of difference between RIA and EIA was negligible and did not change gross interpretation of our results. We found that body condition was higher in recent samples (2003 and 2018) versus older (1992–93) samples. We found corresponding differences in baseline CORT, with higher baseline CORT in older, poorer body condition samples. Hormonal response to acute stress was higher in 2018 relative to 2003. We also found a weak relationship between circulating CORT and bacterial killing ability among 2018 samples, but the biological significance of the relationship is not clear. In an effort to develop hypotheses for future investigation of the links between physiology and demography in this and other systems, we discuss how the changes in CORT and body condition may reflect changes in population dynamics, resource availability or management pressure. Ultimately, we advocate for the synchronization of physiology and management studies to advance the field of applied conservation physiology.
Endpoints for Perianal Crohn’s Disease Trials: Past, Present and Future
Authors: Caron Bénédicte , D’Amico Ferdinando , Danese Silvio , Peyrin-Biroulet Laurent
Published: February 2021

Background and Aims

Since the 1980s, many studies have evaluated the efficacy of therapies to improve the outcomes of patients with perianal Crohn’s disease. We performed a systematic review to describe the evolution of endpoints in perianal fistulizing Crohn’s disease. Efficacy outcomes, definitions and measurement tools were assessed.

Methods

Electronic databases were searched up to November 1, 2020. All published randomized placebo-controlled trials enrolling patients with perianal fistula and Crohn’s disease were eligible for inclusion. Ongoing randomized clinical trials were also described.

Results

Nineteen randomized controlled trials were included. Clinical efficacy endpoints were reported in all trials. Clinical response was the most frequent primary endpoint [6/19 studies, 31.6%], followed by clinical remission in four studies [21%]. Clinical response was defined as closure of at least 50% of fistulas, while remission was defined as closure of all fistulas. A combined clinical and radiological primary endpoint was used to assess fistula healing in four studies [21%]. The Perianal Disease Activity Index was a primary endpoint in only one study [5.5%]. In addition, eight ongoing controlled trials were identified. Combined clinical and radiological remission was the most frequent primary endpoint in these studies [4/8, 50%].

Conclusion

In this systematic review, significant changes in outcomes used in randomized clinical trials of perianal Crohn’s disease were observed. Radiological endpoints are increasingly used in perianal fistulizing Crohn’s disease trials.
Between a hygiene rock and a hygienic hard place
Authors: Parker William , Sarafian Joshua T , Broverman Sherryl A , Laman Jon D
Published: February 2021

Suboptimal understanding of concepts related to hygiene by the general public, clinicians and researchers is a persistent problem in health and medicine. Although hygiene is necessary to slow or prevent deadly pandemics of infectious disease such as coronavirus disease 2019 (COVID-19), hygiene can have unwanted effects. In particular, some aspects of hygiene cause a loss of biodiversity from the human body, characterized by the almost complete removal of intestinal worms (helminths) and protists. Research spanning more than half a century documents that this loss of biodiversity results in an increased propensity for autoimmune disease, allergic disorders, probably neuropsychiatric problems and adverse reactions to infectious agents. The differences in immune function between communities with and communities without helminths have become so pronounced that the reduced lethality of severe acute respiratory syndrome coronavirus 2 in low-income countries compared to high-income countries was predicted early in the COVID-19 pandemic. This prediction, based on the maladaptive immune responses observed in many cases of COVID-19 in high-income countries, is now supported by emerging data from low-income countries. Herein, hygiene is subdivided into components involving personal choice versus components instituted by community wide systems such as sewage treatment facilities and water treatment plants. The different effects of personal hygiene and systems hygiene are described, and appropriate measures to alleviate the adverse effects of hygiene without losing the benefits of hygiene are discussed. Finally, text boxes are provided to function as stand-alone, public-domain handouts with the goal of informing the public about hygiene and suggesting solutions for biomedical researchers and policy makers.

Lay Summary: Hygiene related to sewer systems and other technology can have adverse effects on immune function, and is distinct from personal hygiene practices such as hand washing and social distancing. Dealing with the drawbacks of hygiene must be undertaken without compromising the protection from infectious disease imposed by hygiene.
Changes in the gut microbial community of the eastern newt (Notophthalmus viridescens) across its three distinct life stages
Authors: Fontaine Samantha S , Mineo Patrick M , Kohl Kevin D
Published: February 2021

Understanding the forces that shape vertebrate gut microbial community assembly and composition throughout development is a major focus of the microbiome field. Here, we utilize the complex life cycle of the eastern newt (Notophthalmus viridescens) as a natural wild model to compare the effects of host and environmental factors on gut microbiome development. We compared bacterial inventories of each of the newt's three physiologically distinct developmental stages to determine if each hosted a unique community, or if the two stages which share an aquatic habitat (larvae and adults) harbored more similar communities than those of the third stage, the terrestrial juvenile eft. Additionally, we assessed how the contribution of selective processes to gut microbial assembly changed through development. We found that structurally, each life stage harbored a distinct community, which may be attributable to host factors. Further, across development, we found that community assembly processes shifted from a predominance of neutral to selective forces. However, habitat may also be important in determining community membership and diversity due the uniqueness of eft communities based on these metrics. Our results are similar to those in other vertebrate taxa, suggesting that gut microbiota assembly processes may be conserved across diverse lineages.
Modeling Effects of Overstory Density and Competing Vegetation on Tree Height Growth
Authors: Salas Christian , Stage Albert R. , Robinson Andrew P.
Published: February 2021

We developed and evaluated an individual-tree height growth model for Douglas-fir [Pseudotsuga menziesii (Mirbel) Franco] in the Inland Northwest United States. The model predicts growth for all tree sizes continuously, rather than requiring a transition between independent models for juvenile and mature growth phases. The model predicts the effects of overstory and understory vegetative competition on height growth. Our model requires attained height rather than tree age as a predictor variable, thereby avoiding the problems of site index. Site effects are introduced as a function of ecological habitat type, elevation, aspect, and slope. We used six data sets totaling 3,785 trees in 314 plots. The structure of the data and the model indicated the need for a mixed-effects, nonlinear modeling approach using maximum likelihood in a linear differential equation with a power transformation. Behavior of the model was analyzed using a state-space approach. Our results show that both overstory and understory density affect height growth, allowing a manager to make informed decisions about vegetation control.
The Effects of Fertilization on Soil Respiration in 2-Year-Old Pinus taeda L. Clones
Authors: Tyree Michael C. , Seiler John R. , Fox Thomas R.
Published: February 2021

Fertilization is a common, cost-effective method to increase productivity of managed forests in the southeastern United States; however, little is known about how fertilization will affect the processes that drive total soil CO2 efflux (F S) and ultimately net ecosystem productivity (NEP). The objective of this research was to intensively monitor the response of F S, and its respiratory components during the first year after N and P fertilization in Pinus taeda clones. We monitored F S, heterotrophic respiration (R H), and specific root respiration (R R) and found that F S in fertilized plots differed significantly (P < 0.0001) from that in unfertilized plots, but the direction of this effect was dependent on date. Additionally, R H was consistently lower (P = 0.0001) in fertilized plots relative to control plots, but the magnitude was dependent on the sampling date, and R R significantly (P = 0.04) increased in fertilized plots (+20%) when averaged over the study. Increased R R and decreased R H were probably offsetting each other, resulting in no overall difference in F S 1 year after fertilization. If these short-term trends persisted over the rotation of the stand, increased gross primary productivity accompanied by no change or even a decrease in soil C evolution could result in increased NEP.
A Naturally Heteroplasmic Clam Provides Clues about the Effects of Genetic Bottleneck on Paternal mtDNA
Authors: Iannello Mariangela , Bettinazzi Stefano , Breton Sophie , Ghiselli Fabrizio , Milani Liliana
Published: February 2021

Mitochondrial DNA (mtDNA) is present in multiple copies within an organism. Since these copies are not identical, a single individual carries a heterogeneous population of mtDNAs, a condition known as heteroplasmy. Several factors play a role in the dynamics of the within-organism mtDNA population: among them, genetic bottlenecks, selection, and strictly maternal inheritance are known to shape the levels of heteroplasmy across mtDNAs.

In Metazoa, the only evolutionarily stable exception to the strictly maternal inheritance of mitochondria is the doubly uniparental inheritance (DUI), reported in 100+ bivalve species. In DUI species, there are two highly divergent mtDNA lineages, one inherited through oocyte mitochondria (F-type) and the other through sperm mitochondria (M-type). Having both parents contributing to the mtDNA pool of the progeny makes DUI a unique system to study the dynamics of mtDNA populations. Since, in bivalves, the spermatozoon has few mitochondria (4–5), M-type mtDNA faces a tight bottleneck during embryo segregation, one of the narrowest mitochondrial bottlenecks investigated so far.

Here, we analyzed the F- and M-type mtDNA variability within individuals of the DUI species Ruditapes philippinarum and investigated for the first time the effects of such a narrow bottleneck affecting mtDNA populations. As a potential consequence of this narrow bottleneck, the M-type mtDNA shows a large variability in different tissues, a condition so pronounced that it leads to genotypes from different tissues of the same individual not to cluster together. We believe that such results may help understanding the effect of low population size on mtDNA bottleneck.
Chromosome-wide characterization of meiotic noncrossovers (gene conversions) in mouse hybrids
Authors: Gergelits Vaclav , Parvanov Emil , Simecek Petr , Forejt Jiri
Published: February 2021

During meiosis, the recombination-initiating DNA double-strand breaks (DSBs) are repaired by crossovers or noncrossovers (gene conversions). While crossovers are easily detectable, noncrossover identification is hampered by the small size of their converted tracts and the necessity of sequence polymorphism. We report identification and characterization of a mouse chromosome-wide set of noncrossovers by next-generation sequencing of 10 mouse intersubspecific chromosome substitution strains. Based on 94 identified noncrossovers, we determined the mean length of a conversion tract to be 32 bp. The spatial chromosome-wide distribution of noncrossovers and crossovers significantly differed, although both sets overlapped the known hotspots of PRDM9-directed histone methylation and DNA DSBs, thus supporting their origin in the standard DSB repair pathway. A significant deficit of noncrossovers descending from asymmetric DSBs proved their proposed adverse effect on meiotic recombination and pointed to sister chromatids as an alternative template for their repair. The finding has implications for the molecular mechanism of hybrid sterility in mice from crosses between closely related Mus musculus musculus and Mus musculus domesticus subspecies.
Sex-specific variation in the genome-wide recombination rate
Authors: Peterson April L , Payseur Bret A
Published: February 2021

In most species that reproduce sexually, successful gametogenesis requires recombination during meiosis. The number and placement of crossovers (COs) vary among individuals, with females and males often presenting the most striking contrasts. Despite the recognition that the sexes recombine at different rates (heterochiasmy), existing data fail to answer the question of whether patterns of genetic variation in recombination rate are similar in the two sexes. To fill this gap, we measured the genome-wide recombination rate in both sexes from a panel of wild-derived inbred strains from multiple subspecies of house mice (Mus musculus) and from a few additional species of Mus. To directly compare recombination rates in females and males from the same genetic backgrounds, we applied established methods based on immunolocalization of recombination proteins to inbred strains. Our results reveal discordant patterns of genetic variation in the two sexes. Whereas male genome-wide recombination rates vary substantially among strains, female recombination rates measured in the same strains are more static. The direction of heterochiasmy varies within two subspecies, Mus musculus molossinus and Mus musculus musculus. The direction of sex differences in the length of the synaptonemal complex and CO positions is consistent across strains and does not track sex differences in genome-wide recombination rate. In males, contrasts between strains with high recombination rate and strains with low recombination rate suggest more recombination is associated with stronger CO interference and more double-strand breaks. The sex-specific patterns of genetic variation we report underscore the importance of incorporating sex differences into recombination research.
Heritability of DNA methylation in threespine stickleback (Gasterosteus aculeatus)
Authors: Hu Juntao , Smith Sara J , Barry Tegan N , Jamniczky Heather A , Rogers Sean M , Barrett Rowan D H
Published: February 2021

Epigenetic mechanisms underlying phenotypic change are hypothesized to contribute to population persistence and adaptation in the face of environmental change. To date, few studies have explored the heritability of intergenerationally stable methylation levels in natural populations, and little is known about the relative contribution of cis- and trans-regulatory changes to methylation variation. Here, we explore the heritability of DNA methylation, and conduct methylation quantitative trait loci (meQTLs) analysis to investigate the genetic architecture underlying methylation variation between marine and freshwater ecotypes of threespine stickleback (Gasterosteus aculeatus). We quantitatively measured genome-wide DNA methylation in fin tissue using reduced representation bisulfite sequencing of F1 and F2 crosses, and their marine and freshwater source populations. We identified cytosines (CpG sites) that exhibited stable methylation levels across generations. We found that additive genetic variance explained an average of 24–35% of the methylation variance, with a number of CpG sites possibly autonomous from genetic control. We also detected both cis- and trans-meQTLs, with only trans-meQTLs overlapping with previously identified genomic regions of high differentiation between marine and freshwater ecotypes. Finally, we identified the genetic architecture underlying two key CpG sites that were differentially methylated between ecotypes. These findings demonstrate a potential role for DNA methylation in facilitating adaptation to divergent environments and improve our understanding of the heritable basis of population epigenomic variation.
Altered Blood Cell Traits Underlie a Major Genetic Locus of Severe COVID-19
Authors: Zhou Jingqi , Sun Yitang , Huang Weishan , Ye Kaixiong
Published: February 2021

Background

The genetic locus 3p21.31 has been associated with severe coronavirus disease 2019 (COVID-19), but the underlying pathophysiological mechanism is unknown.

Methods

To identify intermediate traits associated with the 3p21.31 locus, we first performed a phenome-wide association study (PheWAS) with 923 phenotypes in 310 999 European individuals from the UK Biobank. For genes potentially regulated by the COVID-19 risk variant, we examined associations between their expression and the polygenic score (PGS) of 1263 complex traits in a meta-analysis of 31 684 blood samples. For the prioritized blood cell traits, we tested their associations with age and sex in the same UK Biobank sample.

Results

Our PheWAS highlighted multiple blood cell traits to be associated with the COVID-19 risk variant, including monocyte count and percentage (p = 1.07 × 10–8, 4.09 × 10–13), eosinophil count and percentage (p = 5.73 × 10–3, 2.20 × 10–3), and neutrophil percentage (p = 3.23 × 10–3). The PGS analysis revealed positive associations between the expression of candidate genes and genetically predicted counts of specific blood cells: CCR3 with eosinophil and basophil (p = 5.73 × 10–21, 5.08 × 10–19); CCR2 with monocytes (p = 2.40 × 10–10); and CCR1 with monocytes and neutrophil (p = 1.78 × 10–6, 7.17 × 10–5). Additionally, we found that almost all examined white blood cell traits are significantly different across age and sex groups.

Conclusions

Our findings suggest that altered blood cell traits, especially those of monocyte, eosinophil, and neutrophil, may represent the mechanistic links between the genetic locus 3p21.31 and severe COVID-19. They may also underlie the increased risk of severe COVID-19 in older adults and men.
Glacial isostatic adjustment of the Pacific Coast of North America: the influence of lateral Earth structure
Authors: Yousefi Maryam , Milne Glenn A , Latychev Konstantin
Published: February 2021

The Pacific Coast of Central North America is a geodynamically complex region which has been subject to various geophysical processes operating on different timescales. Glacial isostatic adjustment (GIA), the ongoing deformational response of the solid Earth to past deglaciation, is an important geodynamic process in this region. In this study, we apply earth models with 3-D structure to determine if the inclusion of lateral structure can explain the poor performance of 1-D models in this region. Three different approaches are used to construct 3-D models of the Earth structure. For the first approach, we adopt an optimal 1-D viscosity structure from previous work and add lateral variations based on four global seismic shear wave velocity anomalies and two global lithosphere thickness models. The results based on these models indicate that the addition of lateral structure significantly impacts modelled RSL changes, but the data-model fits are not improved. The global seismic models are limited in spatial resolution and so two other approaches were considered to produce higher resolution models of 3-D structure: inserting a regional seismic model into two of the global seismic models and, explicitly incorporating regional structure of the Cascadia subduction zone and vicinity, that is the subducting slab, the overlying mantle wedge and the plate boundary interface. The results associated with these higher resolution models do not reveal any clear improvement in satisfying the RSL observations, suggesting that our estimates of lateral structure are inaccurate and/or the data-model misfits are primarily due to limitations in the adopted ice-loading history. The different realizations of 3-D Earth structure gives useful insight to uncertainty associated with this aspect of the GIA model. Our results indicate that improving constraints on the deglacial history of the southwest sector of the Cordilleran ice sheet is an important step towards developing more accurate of GIA models for this region.
Widening the gap? Unintended consequences of health promotion measures for young people during COVID-19 lockdown
Authors: Alexander Stephanie A , Shareck Martine
Published: February 2021

During the first wave of the COVID-19 pandemic, global measures preventing the spread of the new coronavirus required most of the population to lockdown at home. This sudden halt to collective life meant that non-essential services were closed and many health promoting activities (i.e. physical activity, school) were stopped in their tracks. To curb the negative health impacts of lockdown measures, activities adapting to this new reality were urgently developed. One form of activity promoted indoor physical activity to prevent the adverse physical and psychological effects of the lockdown. Another form of activity included the rapid development of online learning tools to keep children and youth engaged academically while not attending school. While these health promoting efforts were meant to benefit the general population, we argue that these interventions may have unintended consequences and inadvertently increase health inequalities affecting marginalized youth in particular, as they may not reap the same benefits, both social and physical, from the interventions promoting at-home physical activities or distance learning measures. We elaborate on several interventions and their possible unintended consequences for marginalized youth and suggest several strategies that may mitigate their impact.
Location flexibility in parcel delivery operations: framework and empirical analysis
Authors: Krushinsky Dmitry , Guo Xuezhen , Claassen G D H
Published: February 2021

In traditional parcel delivery operations, customers determine delivery locations and, hence, the performance of a transporter. We exploit this idea and show that customers can improve the efficiency of a transporter by giving the latter flexibility in choosing the delivery locations. Two possible policies to enable this flexibility are presented and evaluated. The first policy, conceptually similar to roaming vehicle routing, is related to the presence of alternative locations. The second policy is related to the possibility of aggregating/skipping some locations. We show that route optimization behind both policies can be modelled via the well-known generalized travelling salesman problem. Extensive computational experiments with real parcel delivery data are performed to evaluate the potential of the presented policies and to obtain insights for possible implementation in daily practice. The experiments show that under certain conditions, the two proposed policies can lead to 15 to 20% improvement in the route length and in extreme yet realistic cases up to 40 to 50%. Consequently, the concept of flexible delivery locations has potential for practice, especially in densely populated areas.
Impact of Vaccination on Haemophilus influenzae Type b Carriage in Healthy Children Less Than 5 Years of Age in an Urban Population in Nepal
Authors: Shrestha Sonu , Stockdale Lisa K , Gautam Madhav C , Gurung Meeru , Feng Shuo , Maskey Pratistha , Kerridge Simon , Kelly Sarah , Voysey Merryn , Pokhrel Bhishma , Rajbhandari Piyush , Thorson Stephen , Khadka Bibek , Shah Ganesh , Scherer Karin S , Kelly Dominic , Murdoch David R , Shrestha Shrijana , Pollard Andrew J
Published: February 2021

Background

Reduction in detection of asymptomatic carriage of Haemophilus influenzae type b (Hib) can be used to assess vaccine impact. In Nepal, routine vaccination against Hib in children at 6, 10, and 14 weeks of age was introduced in 2009. Before vaccine introduction, Hib carriage was estimated at 5.0% among children aged <13 years in Nepal, with higher rates among children under 5. Large-scale evaluation of Hib carriage in children has not been investigated since the introduction of the pentavalent diphtheria-tetanus-pertussis/Hib/hepatitis B (DTP-Hib-HepB) vaccine in Nepal.

Methods

A total of 666 oropharyngeal swabs were collected between August and December 2018 from healthy children between 6 months and 5 years of age attending the vaccination clinic at Patan Hospital, Kathmandu, Nepal. Of these 666 swabs, 528 (79.3%) were tested for Hib by culture. Demographic and vaccination data were collected.

Results

Among 528 swabs tested for Hib, 100% came from fully vaccinated children. No swabs were positive for Hib (95% confidence interval, .0–.7). The absence of Hib in 2018 suggests vaccine-induced protection against Hib carriage 9 years after vaccine introduction.

Conclusions

Following 3 doses of pentavalent DTP-Hib-HepB vaccine, Hib carriage in children under the age of 5 years in Nepal is no longer common. Ongoing high coverage with Hib vaccine in early childhood is expected to maintain protection against Hib disease in Nepal.
Comparison of Culture, Antigen Test, and Polymerase Chain Reaction for Pneumococcal Detection in Cerebrospinal Fluid of Children
Authors: Hasanuzzaman Md , Saha Senjuti , Malaker Roly , Rahman Hafizur , Sajib Mohammad S I , Das Rajib C , Islam Maksuda , Hamer Davidson H , Darmstadt Gary L , Saha Samir K
Published: February 2021

Background

Sensitivity of culture for the detection of Streptococcus pneumoniae is limited by prior antibiotic exposure. Immunochromatographic test (ICT) is highly sensitive and specific for pneumococcal antigen detection in the cerebrospinal fluid (CSF) of meningitis cases. We determined the specificity and sensitivity of culture, ICT, and polymerase chain reaction (PCR) and the effect of antibiotic exposure on their performance.

Methods

CSF specimens from suspected meningitis cases admitted to Dhaka Shishu Hospital, Bangladesh, were tested using culture, ICT and PCR. Additionally, 165 specimens collected from 69 pneumococcal cases after antibiotic treatment were tested.

Results

Of 1883 specimens tested, culture detected 9, quantitative PCR (qPCR) detected 184, and ICT detected 207 pneumococcal cases (including all culture and qPCR positives). In comparison to ICT, sensitivity of culture was 4.4% and of qPCR was 90.6%; both were 100% specific. After antibiotic exposure, culture sensitivity plummeted rapidly; conventional PCR and qPCR sensitivity disappeared after day 6 and 20, respectively. ICT detected pneumococcal antigen for >10 weeks.

Conclusions

While culture provides the most information about bacterial characteristics, in high antibiotic exposure settings, ICT exhibits maximum sensitivity. We recommend culture and ICT as mainstay for pneumococcal diagnosis and surveillance; qPCR can generate additional molecular data where possible.
COVID-19 and immunity: quo vadis?
Authors: Miyasaka Masayuki
Published: February 2021

Understanding the precise nature and durability of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in order to gain insight into the pathophysiology of coronavirus disease 2019 (COVID-19) and to develop novel treatment strategies to this disease. Here, I succinctly summarize what is currently known and unknown about the immune response during COVID-19 and discuss whether natural infections can lead to herd immunity.
Habits and Policy: The Social Construction of Foreign Policymaking Processes
Authors: Bertucci Mariano E
Published: February 2021

This article offers an alternative explanation for the processes by which foreign policy is made. It does so across three different countries, across different governments, across issues that had real “blood and treasure” at stake, across different domestic and international contexts, and while holding the target of policy, the United States, constant. Available theories argue that formal political institutions or norms determine who will influence the making of policy and how they will do so. However, Argentina, Brazil, and Chile—countries with strikingly similar formal rules for making foreign policy—have been following, for decades, fundamentally different foreign policymaking processes, and they have been doing so without resorting to any normative justifications. The article contrasts the theoretical expectations of rational choice institutionalism and norm-based arguments on foreign policymaking with a logic of habit not captured by the logics of consequences or appropriateness of rational choice institutionalism and norm-based explanations. The article makes two contributions. First, it furthers the theoretical development of the concept of habit in international relations and offers a means of studying habits empirically. Second, it challenges the assumption that the power of domestic actors in foreign policy is a function of formal institutions or prevailing norms.
Hagiography Unbound: A Theory of Making and Using Holy Media
Authors: Hollander Aaron T
Published: February 2021

Hagiography is a scholarly category that has been used primarily to group textual sources that represent the lives of Christian saints. This article contends that the utility of hagiography and hagiographical far exceeds this commonplace usage, in terms of both the ways they entail broadly enacted cultural dynamics and their applicability beyond conventional disciplinary expectations of what constitutes representations of saints (or even religious content). The article provides a retheorization along two analytic vectors: (1) framing hagiography in terms of a field of many interconnected media rather than identifying it with texts alone, and (2) studying it in terms of the psychosocial processes (imagination, representation, and appropriation) that generate and mobilize understandings of holiness in the world rather than limiting it to the products that instantiate but do not exhaust these processes.
Small molecule natural products in human nasal/oral microbiota
Authors: Barber Colin Charles , Zhang Wenjun
Published: February 2021

Small molecule natural products are a chemically diverse class of biomolecules that fulfill myriad biological functions, including autoregulation, communication with microbial neighbors and the host, interference competition, nutrient acquisition, and resistance to oxidative stress. Human commensal bacteria are increasingly recognized as a potential source of new natural products, which may provide insight into the molecular ecology of many different human body sites as well as novel scaffolds for therapeutic development. Here, we review the scientific literature on natural products derived from residents of the human nasal/oral cavity, discuss their discovery, biosynthesis, and ecological roles, and identify key questions in the study of these compounds.
Disruption of the Trichoderma reesei gul1 gene stimulates hyphal branching and reduces broth viscosity in cellulase production
Authors: Zhao Qinqin , Liu Qin , Wang Qi , Qin Yuqi , Zhong Yaohua , Gao Liwei , Liu Guodong , Qu Yinbo
Published: February 2021

Hyphal morphology is considered to have a close relationship with the production level of secreted proteins by filamentous fungi. In this study, the gul1 gene, which encodes a putative mRNA-binding protein, was disrupted in cellulase-producing fungus Trichoderma reesei. The hyphae of Δgul1 strain produced more lateral branches than the parent strain. Under the condition for cellulase production, disruption of gul1 resulted in smaller mycelial clumps and significantly lower viscosity of fermentation broth. In addition, cellulase production was improved by 22% relative to the parent strain. Transcriptome analysis revealed that a set of genes encoding cell wall remodeling enzymes as well as hydrophobins were differentially expressed in the Δgul1 strain. The results suggest that the regulatory role of gul1 in cell morphogenesis is likely conserved in filamentous fungi. To our knowledge, this is the first report on the engineering of gul1 in an industrially important fungus.