bluuebunny/crossref_metadata_2025 huggingface dataset:
Secreted TAL effectors protect symbiotic bacteria from entrapment within fungal hyphae
Authors: Richter Ingrid , Uzum Zerrin , Stanley Claire E. , Moebius Nadine , Stinear Timothy P. , Pidot Sacha J. , Ferling Iuliia , Hillmann Falk , Hertweck Christian
Published: March 2020

The association of the agriculturally significant phytopathogenic fungusRhizopus microsporuswith the bacterial endosymbiontBurkholderia rhizoxinicais a remarkable example of bacteria controlling host physiology and reproduction. Here, we show that a group of transcription activator-like effectors (TALEs) calledBurkholderiaTALE-like proteins (BATs) fromB. rhizoxinicaare essential for the establishment of the symbiosis. Mutants lacking BAT proteins are unable to induce host sporulation. Utilising novel microfluidic devices in combination with fluorescence microscopy we observed the accumulation of BAT-deficient mutants in specific fungal side-hyphae with accompanying increased fungal re-infection. High-resolution live imaging revealed septa biogenesis at the base of infected hyphae leading to compartmental trapping of BATdeficient endobacteria. Trapped endosymbionts showed reduced intracellular survival, suggesting a protective response from the fungal host against bacteria lacking specific effectors. These findings underscore the involvement of BAT proteins in maintaining a balance between mutualism and antagonism in bacterial-fungal interactions and provide deeper insights into the dynamic interactions between bacteria and eukaryotes.
What is the storage effect, why should it occur in cancers, and how can it inform cancer therapy?
Authors: Miller Anna K. , Brown Joel S. , Basanta David , Huntly Nancy
Published: March 2020

Intratumor heterogeneity is a feature of cancer that is associated with progression, treatment resistance, and recurrence. However, the mechanisms that allow diverse cancer cell lineages to coexist remain poorly understood. The storage effect is a coexistence mechanism that has been proposed to explain the diversity of a variety of ecological communities, including coral reef fish, plankton and desert annual plants. Three ingredients are required for there to be a storage effect: 1) temporal variability in the environment, 2) buffered population growth, and 3) species-specific environmental responses. Here, we argue that these conditions are observed in cancers and that it is likely that the storage effect contributes to intratumor diversity. Data that show the temporal variation within the tumor microenvironment is needed to quantify how cancer cells respond to fluctuations in the tumor microenvironment and what impact this has on interactions among cancer cell types. The presence of a storage effect within a patient’s tumors could have substantial impact on how we understand and treat cancer.
Melatonin Protects T-2 toxin-induced neuronal stress through Acetylcholinesterase & Cytochrome P450 receptor-mediated signaling
Authors: Maroli Nikhil
Published: March 2020

T-2 toxin is one of the potent mycotoxins responsible for several pathological conditions in humans and animals. This nonvolatile low molecular weight toxin compound shows strong resistance to degradation at room temperature as well as at autoclaving temperature. The inhibition of acetylcholinesterase and cytochrome P450 receptor by T-2 toxin leads to many pathological conditions as these two receptors involved in many pathways. Here, we have used melatonin as a protection agent against T-2 toxin in both receptor systems. Using molecular docking, molecular dynamics simulation and free energy calculations we have shown that melatonin can act as a potent inhibitor of T-2 toxin in acetylcholinesterase and cytochrome P450.
Bacterial envelope damage inflicted by bioinspired nanospikes grown in a hydrogel
Authors: Arias Sandra L. , Devorkin Joshua , Spear Jessica C. , Civantos Ana , Allain Jean Paul
Published: March 2020

Device-associated infections are one of the deadliest complications accompanying the use of biomaterials, and despite recent advances in the development of anti-biofouling strategies, biomaterials that exhibit both functional tissue restoration and antimicrobial activity have been challenging to achieve. Here, we report the fabrication of bio-inspired bactericidal nanospikes in bacterial cellulose and investigate the mechanism underlying this phenomenon. We demonstrate these structures affects preferentially stiff membranes like those in Gram-positive bacteria, but exhibit cytocompatibility towards mammalian cells, a requisite for tissue restoration. We also reveal the bactericidal activity of the nanospikes is due to a pressure-induced mechanism, which depends on the cell’s adherence time, nanospike’s geometry and spacing, cell shape, and mechanical properties of the cell wall. Our findings provide a better understanding of the mechanobiology of bacterial cells at the interface with nanoscale structures, which is fundamental for the rational design bactericidal topographies.
Coupled Co-clustering-based Unsupervised Transfer Learning for the Integrative Analysis of Single-Cell Genomic Data
Authors: Zeng Pengcheng , WangWu Jiaxuan , Lin Zhixiang
Published: March 2020

Unsupervised methods, such as clustering methods, are essential to the analysis of single-cell genomic data. Most current clustering methods are designed for one data type only, such as scRNA-seq, scATAC-seq or sc-methylation data alone, and a few are developed for the integrative analysis of multiple data types. Integrative analysis of multimodal single-cell genomic data sets leverages the power in multiple data sets and can deepen the biological insight. We propose a coupled co-clustering-based unsupervised transfer learning algorithm (coupleCoC) for the integrative analysis of multimodal single-cell data. Our proposedcoupleCoC builds upon the information theoretic co-clustering framework. We appliedcoupleCoC for the integrative analysis of scATAC-seq and scRNA-seq data, sc-methylation and scRNA-seq data, and scRNA-seq data from mouse and human. We demonstrate thatcoupleCoC improves the overall clustering performance and matches the cell subpopulations across multimodal single-cell genomic data sets. The software and data sets are available athttps://github.com/cuhklinlab/coupleCoC.
TDP-43 and HSP70 phase separate into anisotropic, intranuclear liquid spherical annuli
Authors: Yu Haiyang , Lu Shan , Gasior Kelsey , Singh Digvijay , Tapia Olga , Vazquez-Sanchez Sonia , Toprani Divek , Beccari Melinda S. , Yates John R. , Da Cruz Sandrine , Newby Jay M. , Larfaga Miguel , Gladfelter Amy S. , Villa Elizabeth , Cleveland Don W.
Published: March 2020

The RNA binding protein TDP-43 naturally phase separates within cell nuclei and forms cytoplasmic aggregates in age-related neurodegenerative diseases. Here we show that acetylation-mediated inhibition of TDP-43 binding to RNA produces co-de-mixing of acetylated and unmodified TDP-43 into symmetrical, intranuclear spherical annuli whose shells and cores have liquid properties. Shells are anisotropic, like liquid crystals. Consistent with our modelling predictions that annulus formation is driven by components with strong self-interactions but weak interaction with TDP-43, the major components of annuli cores are identified to be HSP70 family proteins, whose chaperone activity is required to maintain liquidity of the core. Proteasome inhibition, mimicking reduction in proteasome activity during aging, induces TDP-43-containing annuli in neurons in rodents. Thus, we identify that TDP-43 phase separation is regulated by acetylation, proteolysis, and ATPase-dependent chaperone activity of HSP70.

One Sentence Summary

Acetylation of TDP-43 drives its phase separation into spherical annuli that form a liquid-inside-a-liquid-inside-a-liquid.
Factors influencing swift and effective resolution of supplier problems
Authors: Clemons Rebecca , Baddam Swathi Reddy , Henry Raymond M.
Published: March 2020

Purpose

How might an organization swiftly resolve supplier problems such that the issue does not reoccur? The purpose of this study seeks to understand the impact of different knowledge-sharing routines on measures of effective problem resolution.

Design/methodology/approach

Data are collected from an automotive manufacturer's (buyer) database. A hierarchical linear model analyzes dyadic data collected from 155 problems across 24 suppliers.

Findings

This study reveals that different ways of communicating have differing impact on measures of effective problem-solving. Communication involving face-to-face interaction slows the process, whereas frequent communication can lead to swift resolution. Furthermore, management teams are more likely to lead to a “better” fix in that these teams are more likely to implement changes in the process or product.

Research limitations/implications

The data are for a tier-one automotive supplier. Hence, the findings are limited by the extent to which other organizations may differ.

Practical implications

The results provide insights for managers experiencing supply issues. Some forms of communication should be encouraged as they enhance the process. Moreover, the findings suggest there are consequences to pressuring a supplier to resolve a complaint quickly.

Originality/value

Very few researchers can claim to have investigated observed collaborative mechanisms that occur between a buyer and its suppliers when resolving a problem. This research adds to the literature on the relational view theory as it applies to supply chain management and problem resolution.
Transforming growth factor‐β promotes the function of HIV‐specific CXCR5+CD8 T cells
Authors: Yang Hong‐Ge , Jiao Yan‐Mei , Huang Hui‐Huang , Zhang Chao , Zhang Ji‐Yuan , Xu Ruo‐Nan , Song Jin‐Wen , Fan Xing , Jin Lei , Shi Ming , Wang Fu‐Sheng
Published: March 2020

HIV replication can be inhibited by CXCR5+CD8 T cells (follicular cytotoxic T cell [TFC]) which transfer into B‐cell follicles where latent HIV infection persists. However, how cytokines affect TFC remain unclear. Understanding which cytokines show the ability to affect TFC could be a key strategy toward curing HIV. Similar mechanisms could be used for the growth and transfer of TFCs and follicular helper T (TFH) cells; as a result, we hypothesized that cytokines IL‐6, IL‐21, and transforming growth factor‐β (TGF‐β), which are necessary for the differentiation of TFH cells, could also dictate the development of TFCs. In this work, lymph node mononuclear cells and peripheral blood mononuclear cells from HIV‐infected individuals were cocultured with IL‐6, IL‐21, and TGF‐β. We then carried out T‐cell receptor (TCR) repertoire analysis to compare the differences between CXCR5– and CXCR5+CD8 T cells. Our results showed that the percentage and function of TFC can be enhanced by stimulation with TGF‐β. Besides, TGF‐β stimulation enhanced the diversity of TCR and complementarity‐determining region 3 sequences. HIV DNA showed a negative correlation with TFC. The use of TGF‐β to promote the expression of CXCR5+CD8 T cells could become a new treatment approach for curing HIV.
Genomic characterization of antibiotic resistance‐encoding genes in clinical isolates of Vibrio cholerae non‐O1/non‐O139 strains from Kolkata, India: generation of novel types of genomic islands containing plural antibiotic resistance genes
Authors: Morita Daichi , Takahashi Eizo , Morita Masatomo , Ohnishi Makoto , Mizuno Tamaki , Miyoshi Shin‐ichi , Dutta Devarati , Ramamurthy Thandavarayan , Chowdhury Goutam , Mukhopadhyay Asish K. , Okamoto Keinosuke
Published: March 2020

Non‐O1/non‐O139 nontoxigenic Vibrio cholerae associated with cholera‐like diarrhea has been reported in Kolkata, India. However, the property involved in the pathogenicity of these strains has remained unclear. The character of 25 non‐O1/non‐O139 nontoxigenic V. cholerae isolated during 8 years from 2007 to 2014 in Kolkata was examined. Determination of the serogroup showed that the serogroups O6, O10, O35, O36, O39, and O70 were represented by two strains in each serogroup, and the remaining isolates belonged to different serogroups. To clarify the character of antibiotic resistance of these isolates, an antibiotic resistance test and the gene analysis were performed. According to antimicrobial drug susceptibility testing, 13 strains were classified as drug resistant. Among them, 10 strains were quinolone resistant and 6 of the 13 strains were resistant to more than three antibiotics. To define the genetic background of the antibiotic character of these strains, whole‐genome sequences of these strains were determined. From the analysis of these sequences, it becomes clear that all quinolone resistance isolates have mutations in quinolone resistance‐determining regions. Further research on the genome sequence showed that four strains possess Class 1 integrons in their genomes, and that three of the four integrons are found to be located in their genomic islands. These genomic islands are novel types. This indicates that various integrons containing drug resistance genes are spreading among V. cholerae non‐O1/non‐O139 strains through the action of newly generated genomic islands.
Consistent metacommunity structure despite inconsistent drivers of assembly at the continental scale
Authors: Murray‐Stoker David , Murray‐Stoker Kelly M.
Published: March 2020

A fundamental goal of community ecology is to understand the drivers of community assembly and diversity. Local factors acting on community assembly are typically related to environmental conditions while regional factors are typically related to dispersal. Previous research has not consistently demonstrated the importance of local or regional factors, but this is likely because these factors act in concert and not in isolation. Studies that simultaneously integrate local and regional factors into analyses of community assembly can be a useful avenue to further our understanding of this core concept in community ecology.

Here, we aimed to identify metacommunity structure and diversity and the local and regional drivers of community assembly at the continental scale.

We evaluated metacommunity structure and drivers of assembly of macroinvertebrate communities in 941 rivers and streams nested within nine ecoregions distributed across the conterminous United States. Pattern‐based metacommunity analyses and boosted regression tree techniques were used to (a) assign metacommunity structures and (b) identify the environmental, landscape and network drivers of assembly. We also evaluated how biodiversity scaled across hierarchical levels and varied among ecoregions.

Metacommunity structures were consistent for the conterminous United States and each of the nine ecoregion subsets, with each ecoregional metacommunity displaying a Clementsian structure. Environmental variables were the predominant drivers of assembly, suggesting the importance of species sorting and environmental filtering on community structure; however, the identity of the most influential environmental variables differed among ecoregions and suggested hierarchical filtering on assembly. Partitioned diversity was found to be lower at the local and ecoregional levels, but turnover in diversity among ecoregions was higher than expected.

Our results demonstrate contingencies in community assembly, notwithstanding consistency in metacommunity structure and support the importance of environmental control over community assembly and biodiversity. Moreover, biodiversity at the continental scale is likely maintained through this inherent variation in the drivers of assembly and concomitant changes in community composition among ecoregions. We suggest that further work should evaluate the assembly of other facets of community structure and the underlying mechanisms of the contingency in assembly drivers.
Recent biological invasion shapes species recognition and aggressive behaviour in a native species: A behavioural experiment using robots in the field
Authors: Dufour Claire M. S. , Clark David L. , Herrel Anthony , Losos Jonathan B.
Published: March 2020

Invasive species are a world‐wide threat to biodiversity. Yet, our understanding of biological invasions remains incomplete, partly due to the difficulty of tracking and studying behavioural interactions in recently created species interactions.

We tested whether the interactions between the recently introduced invasive lizard Anolis cristatellus and the native Anolis oculatus in Dominica have led to changes in species recognition and aggressive behaviour of the native species.

The use of realistic robots allowed us to test the behavioural response of 131 A. oculatus males towards relevant and controlled conspecific versus heterospecific stimuli, directly in the field and in two contexts (allopatry vs. sympatry).

Our results show that species recognition evolved prior to sympatry in A. oculatus. Moreover, interspecific competition resulted in an increase in the time spent displaying and a divergence in the aggressive behaviour of the native species towards conspecifics versus heterospecifics. Inherent species recognition and higher aggressive behaviour may limit species coexistence as they are expected to favour A. oculatus during territorial interactions with A. cristatellus.

While more studies are needed to understand the causes of these behavioural shifts and their consequences on long‐term species coexistence, the present study highlights the role of behaviour as a first response to interspecific interactions.
Tryptophan 387 and 390 residues in ADAMTS13 are crucial to the ability of vascular tube formation and cell migration of endothelial cells
Authors: Liu Ling , Ma Zhenni , Zhou Xuemei , Yin Jie , Lu Jun , Su Jian , Shen Fei , Xie Liqian , Hu Shaoyan , Ling Jing
Published: March 2020

A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) was mainly generated and secreted from endothelial cells (ECs). Our previous study showed that tryptophan (Trp) residues at 387 and 390 in ADAMTS13 are required for its secretion and enzymatic activity. However, the effects on its host cell as well as the potential mechanism have not been clear. The aim of the study was to examine the effects of Trp residues 387 and 390 of ADAMTS13 on the biological processes of ECs. Herein, Trp was substituted with alanine in ADAMTS13 to generate ADAMTS13 mutants at 387 (W387A), 390 (W390A), and double mutants at 387 and 390 (2WA), respectively. We found that substitution mutation impaired vascular endothelial growth factor (VEGF) secretion and the downstream JAK1/STAT3 activation, the binding ability to Von Willebrand factor, cell proliferation, migration, and vascular tube formation. Overall, our study concluded that Trp387 and Trp390 of ADAMTS13 play vital roles in the biological function of ECs.
Changes in the community structure of anurans in the Coastal plain forest, southeastern Brazil
Authors: Pereira‐Ribeiro Juliane , Ferreguetti Átilla C. , Bergallo Helena G. , Rocha Carlos Frederico D.
Published: March 2020

In this study, we analyzed how variations in species richness, composition and abundance of anurans in a community could be explained by temporal environmental factors such as temperature and precipitation and spatially between different vegetation types. The study was carried out in Vale Natural Reserve, state of Espírito Santo, Brazil, from June 2015 to October 2016. We sampled the anuran community in 21 plots of 250 m in length, with 10 m of width. We recorded a total of 326 individuals of anurans, corresponding to 23 species in six families. We concluded that the anurans community of the Vale Natural Reserve remained relatively stable throughout the seasons and along vegetation types in terms of richness but differed in composition and abundance. The anurans were more abundant in the rainy season, with precipitation being the most important factor for anuran density in the area. Anuran community composition varied among vegetation types due to differences in complexity and structure of each vegetation type. Our study showed that different factors were determinant for the variation in species abundance and composition in the area. Therefore, the conservation of fragments and their associated habitat and the monitoring of environmental changes is of fundamental importance in anuran conservation in the area.
Effect of high hydrostatic pressure challenge on biogenic amines, microbiota, and sensory profile in traditional poultry‐ and pork‐based semidried fermented sausage
Authors: Borges Ana F. , Cózar Almudena , Patarata Luís , Gama Luis T. , Alfaia Cristina M. , Fernandes Maria J. , Fernandes Maria H. , Pérez Herminia Vergara , Fraqueza Maria J.
Published: March 2020

The processing of traditional poultry‐ and pork‐based semidried fermented smoked sausages needs to be modernized to improve product quality and further extend its shelf life. The aim of the present study was to apply different combinations of high pressure (300 to 600 MPa) and time (154 to 1,800 s) on the sausages using an experimental design based on response surface methodology. The chemical, microbial, and sensory characteristics of sausages treated with high‐pressure processing (HPP) were investigated. HPP application to semidried fermented sausages resulted in color changes, which could be dependent on the ingredients, formulation, and smoking conditions used. Nevertheless, none of the HPP treatments applied resulted in detectable changes in sensory properties, as tested in a triangle test and confirmed by the analysis of focus groups assessment. Significant differences were detected for lactic acid bacteria (LAB) counts from 344 MPa and 1,530 s onward, with a marked decrease for the combination of 600 MPa and 960 s (P < 0.05). Coagulase‐negative staphylococci showed higher tolerance to the increase in pressure than LAB. HPP induced a microbial reduction on Enterobacteriaceae, molds, and yeasts, minimizing the production of the main biogenic amines. However, the polyamines (spermine and spermidine) increased since their metabolic use by microorganisms did not occur. Given the reduction of the main spoilage microbial indicators with no detectable sensory changes observed with the binomial condition of 600 MPa and 960 s, this was chosen as the optimal combination to be further applied.

Practical Application

The results from sensory analysis revealed that any of the HPP treatments applied resulted in detectable changes in sensory properties, as tested in a triangle test and confirmed by the analysis of the focus groups speeches.
SuperCRUNCH: A bioinformatics toolkit for creating and manipulating supermatrices and other large phylogenetic datasets
Authors: Portik Daniel M. , Wiens John J.
Published: March 2020

Phylogenies with extensive taxon sampling have become indispensable for many types of ecological and evolutionary studies. Many large‐scale trees are based on a ‘supermatrix’ approach, which involves amalgamating thousands of published sequences for a group. Constructing up‐to‐date supermatrices can be challenging, especially as new sequences may become available almost constantly. Additionally, genomic datasets (composed of thousands of loci) are becoming common in phylogenetics and phylogeography, and present novel challenges for constructing such datasets.

Here we present SuperCRUNCH, a Python toolkit for assembling large phylogenetic datasets. It can be applied to GenBank sequences, unpublished sequences or combinations of GenBank and unpublished data. SuperCRUNCH constructs local databases and uses them to conduct rapid searches for user‐specified sets of taxa and loci. Sequences are parsed into putative loci and passed through rigorous filtering steps. A post‐filtering step allows for selection of one sequence per taxon (i.e. species‐level supermatrix) or retention of all sequences per taxon (i.e. population‐level dataset). Importantly, SuperCRUNCH can generate ‘vouchered’ population‐level datasets, in which voucher information is used to generate multi‐locus phylogeographic datasets. SuperCRUNCH offers many options for taxonomy resolution, similarity filtering, sequence selection, alignment and file manipulation.

We demonstrate the range of features available in SuperCRUNCH by generating a variety of phylogenetic datasets. Output datasets include traditional species‐level supermatrices, large‐scale phylogenomic matrices and phylogeographic datasets. Finally, we briefly compare the ability of SuperCRUNCH to construct species‐level supermatrices relative to alternative approaches. SuperCRUNCH generated a large‐scale supermatrix (1,400 taxa and 66 loci) from 16 GB of GenBank data in ~1.5 hr, and generated population‐level datasets (<350 samples, <10 loci) in <1 min. It outperformed alternative methods for supermatrix construction in terms of taxa, loci and sequences recovered.

SuperCRUNCH is a modular bioinformatics toolkit that can be used to assemble datasets for any taxonomic group and scale (kingdoms to individuals). It allows rapid construction of supermatrices, greatly simplifying the process of updating large phylogenies with new data. It is also designed to produce population‐level datasets. SuperCRUNCH streamlines the major tasks required to process phylogenetic data, including filtering, alignment, trimming and formatting. SuperCRUNCH is open‐source, documented and available at https://github.com/dportik/SuperCRUNCH.
Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model
Authors: Deng Manfei , Zhang Qingping , Wu Zhuoze , Ma Tian , He Aodi , Zhang Tongmei , Ke Xiao , Yu Quntao , Han Yunyun , Lu Youming
Published: March 2020

Recently, we have reported that dentate mossy cells (MCs) control memory precision via directly and functionally innervating local somatostatin (SST) inhibitory interneurons. Here, we report a discovery that dysfunction of synaptic transmission between MCs and SST cells causes memory imprecision in a mouse model of early Alzheimer's disease (AD). Single‐cell RNA sequencing reveals that miR‐128 that binds to a 3′UTR of STIM2 and inhibits STIM2 translation is increasingly expressed in MCs from AD mice. Silencing miR‐128 or disrupting miR‐128 binding to STIM2 evokes STIM2 expression, restores synaptic function, and rescues memory imprecision in AD mice. Comparable findings are achieved by directly engineering MCs with the expression of STIM2. This study unveils a key synaptic and molecular mechanism that dictates how memory maintains or losses its details and warrants a promising target for therapeutic intervention of memory decays in the early stage of AD.
Brief Report: Opioid‐Involved Overdose Mortality in United States Veterans
Authors: Peltzman Talya , Ravindran Chandru , Schoen Patrick M. , Morley Sybil W. , Drexler Karen , Katz Ira R. , McCarthy John F.
Published: March 2020

Background and Objectives

The purpose of this study is to assess trends in opioid‐involved overdose mortality among US Veterans.

Methods

Age‐adjusted drug overdose mortality rates, overall and by opioid subtype, were assessed from National Death Index data for US Veterans; statistical significance of trends was assessed for 2010 to 2015 and 2015 to 2016.

Results

Veteran age‐adjusted overdose mortality rates increased 23.7% from 2010 to 2015 (19.7‐24.4 of 100 000) and a further 20.4% through 2016 (29.3 of 100 000). Opioid involvement increased from 51.3% in 2010 to 62.1% in 2016, as opioid overdose rates increased from 10.9 to 19.5 of 100 000. Overdose mortality varied substantially by opioid subtype and demographics.

Conclusions and scientific significance

This report provides the first‐ever description of trends and characteristics of overdose mortality and opioid‐involved deaths among US Veterans of military service for the period 2010 to 2016. With the exception of female Veterans and Veterans in Western States, it has been found that trends in Veteran overdose mortality paralleled rising rates of drug overdose observed in the United States more broadly. Published 2020. This article is a U.S. Government work and is in the public domain in the USA. (Am J Addict 2020;00:00–00)
A novel homozygous variant in NLRP5 is associate with human early embryonic arrest in a consanguineous Chinese family
Authors: Xu Yao , Qian Ying , Liu Yu , Wang Qiaofeng , Wang Rongxiang , Zhou Yiwen , Zhang Caixia , Pang Zhi , Ye Hongjuan , Xue Songguo , Sun Lihua
Published: March 2020

Early embryonic arrest is one of the major causes of recurrent assisted reproduction failure. It is characterized by delayed embryonic development and failure to form viable eight‐cell stage embryos on day 3 of an assisted reproduction cycle. A recent study reported that biallelic mutations in NLRP5 can cause early embryonic arrest. NLRP5 is a member of subcortical maternal complex, which plays a significant role in embryogenesis. In this study, we described a female in a consanguineous Chinese family who displayed clinical features of early embryonic arrest and identified a novel homozygous variant c.1061C>T (p.Pro354Leu) in NLRP5. This is the second report of the biallelic NLRP5 variant that associates with early embryonic arrest in humans, further confirming the role of NLRP5 variants in early embryonic arrest and expanding the spectrum of known pathogenic variants in NLRP5.
The phylogeny of the Casque‐headed Treefrogs (Hylidae: Hylinae: Lophyohylini)
Authors: Blotto Boris L. , Lyra Mariana L. , Cardoso Monica C.S. , Trefaut Rodrigues Miguel , R. Dias Iuri , Marciano‐Jr Euvaldo , Dal Vechio Francisco , Orrico Victor G.D. , Brandão Reuber A. , Lopes de Assis Clodoaldo , Lantyer‐Silva Amanda S.F. , Rutherford Mike G. , Gagliardi‐Urrutia Giussepe , Solé Mirco , Baldo Diego , Nunes Ivan , Cajade Rodrigo , Torres Ambrosio , Grant Taran , Jungfer Karl‐Heinz , da Silva Helio R. , Haddad Célio F.B. , Faivovich Julián
Published: March 2020

The South American and West Indian Casque‐headed Treefrogs (Hylidae: Hylinae: Lophyohylini) include 85 species. These are notably diverse in morphology (e.g. disparate levels of cranial hyperossification) and life history (e.g. different reproductive modes, chemical defences), have a wide distribution, and occupy habitats from the tropical rainforests to semiarid scrubland. In this paper, we present a phylogenetic analysis of this hylid tribe based on sequence fragments of up to five mitochondrial (12S,16S,ND1,COI,Cytb) and six nuclear genes (POMC,RAG‐1,RHOD,SIAH,TNS3,TYR). We included most of its species (> 96%), in addition to a number of new species. Our results indicate: (i) the paraphyly ofTrachycephaluswith respect toAparasphenodon venezolanus; (ii) the nonmonophyly ofAparasphenodon, withArgenteohyla siemersi,Corythomantis galeataandNyctimantis rugicepsnested within it, andAp. venezolanusnested withinTrachycephalus; (iii) the polyphyly ofCorythomantis; (iv) the nonmonophyly of the recognized species groups ofPhyllodytes; and (v) a pervasive low support for the deep relationships among the major clades of Lophyohylini, includingC. greeningiand the monotypic generaItapotihylaandPhytotriades. To remedy the nonmonophyly ofAparasphenodon,Corythomantis, andTrachycephalus, we redefinedNyctimantisto includeAparasphenodon(with the exception ofAp. venezolanus, which we transferred toTrachycephalus),Argenteohyla, andC. galeata. Additionally, our results indicate the need for taxonomic work in the following clades: (i)Trachycephalus dibernardoiandTr. imitatrix; (ii)Tr. atlas,Tr. mambaiensisandTr. nigromaculatus; and (iii)Phyllodytes. On the basis of our phylogenetic results, we analyzed the evolution of skull hyperossification and reproductive biology, with emphasis on the multiple independent origins of phytotelm breeding, in the context of Anura. We also analyzed the inter‐related aspects of chemical defences, venom delivery, phragmotic behaviour, co‐ossification, and prevention of evaporative water loss.
A Practice‐Based, Clinical Pharmacokinetic Study to Inform Levetiracetam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration (PADRE‐01)
Authors: Kalaria Shamir N. , Armahizer Michael , McCarthy Paul , Badjatia Neeraj , Gobburu Jogarao V. , Gopalakrishnan Mathangi
Published: March 2020

Limited data exist on the effect of continuous renal replacement therapy (CRRT) methods on anti‐epileptic drug pharmacokinetics (PK). This prospective practice‐based PK study aims to assess the impact of continuous venovenous hemofiltration (CVVH), a modality of CRRT, on levetiracetam PK in critically ill patients and to derive individualized dosing recommendations. Eleven patients receiving oral or intravenous levetiracetam and CVVH in various intensive care units at a large academic medical center were enrolled to investigate the need for dosing adjustments. Prefilter, postfilter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1‐hour postoral dose, and up to 6 additional time points postinfusion or postoral administration. Patient‐specific blood and ultrafiltrate flow rates and laboratory values were also collected at the time of sampling. The average sieving coefficient (SC) for levetiracetam was 0.89 ± 0.1, indicating high filter efficiency. Six of the 11 patients experienced concentrations outside the reported therapeutic range (12–46 mg/L). The average volume of distribution was 0.73 L/kg. CVVH clearance contributes a major fraction of the total levetiracetam clearance (36–73%) in neurocritically ill patients. The average bias and precision of the estimated vs. observed total clearance value was ~ 10.6% and 21.5%. Major dose determinants were identified to be SC and effluent flow rate. Patients with higher ultrafiltrate rates will have increased drug clearance and, therefore, will require higher doses in order to match exposures seen in patients with normal renal function.
Encouraging kids to beat: Children's beat gesture production boosts their narrative performance
Authors: Vilà‐Giménez Ingrid , Prieto Pilar
Published: March 2020

Gesture is an integral part of language development. While recent evidence shows that observing a speaker who is simultaneously producing beat gestures helps preschoolers remember and understand information and also improves the production of oral narratives, little is known about the potential value of encouraging children to produce beat gestures—as opposed to merely observing them. In this between‐subjects pretest–posttest training study we examine whether encouraging children to produce beats can boost their narrative performance. A total of 47 5‐ to 6‐year‐old children were divided into two groups and exposed to a training session in which a total of six stories were presented under one of two experimental conditions: (a) the children merely observed video‐recordings of a storyteller who used beat gestures and were then asked to retell the narratives; or (b) the children observed the same video‐recordings and then retold the narratives but were encouraged to simultaneously use their hands in the same way the storytellers did. Pretests and posttests consisting of children's narrations of short animated cartoons were analysed for narrative structure and fluency. A comparison of scores showed that children in the group that had been encouraged to use beat gestures in the training phase performed better in both narrative structure and fluency than the group of children who were simply asked to retell the story without gesture instruction. These findings suggest that linguistically relevant body movements serve to boost language development and that embodied storytelling can be of help in narrative training.
Grazing and productivity alter individual grass size dynamics in semi‐arid woodlands
Authors: Travers Samantha K. , Berdugo Miguel
Published: March 2020

The spatial arrangement of perennial vegetation is critical for ecosystem function in drylands. While much is known about how vegetation patches respond to grazing and abiotic conditions, the size dynamics of individual plants is mostly limited to theoretical studies. We measured the size distribution (mean, variance, skewness) and density of individual grasses, and grass species composition at 451 sites spanning a range of grazing intensities across three broad vegetation communities in semi‐arid eastern Australia. We assessed the relative role of grazing by livestock (cattle and sheep), native (kangaroos) and introduced (rabbits) free ranging herbivores, and several environmental measures (productivity, diversity, composition and groundstorey plant cover) on the size distribution and density of individual grasses. We found mean grass size and density were more sensitive to shifts in grazing intensity and environmental conditions than size variance or the frequency of the smallest individuals (skewness), and shifts were mostly driven by site productivity and cattle and kangaroo grazing. Sheep grazing only reduced mean grass size, and rabbit grazing had no consistent effects. Importantly, we found that site productivity and species composition altered the impacts of grazing on grass density and size distribution. For example, increasing cattle grazing led to larger grasses in low productivity sites. It also led to larger, denser, more variable‐sized grasses among grass species from sites with finer soil texture. Increasing kangaroo grazing led to smaller, denser individuals among grass species from sites with coarse soil texture. At high diversity sites kangaroo grazing led to denser, more homogenised grass sizes with a lower frequency of small individuals. Understanding the in situ response of individual plant sizes gives us insights into the processes driving shifts in perennial vegetation patchiness, improving our ability to predict how the spatial arrangement of ecosystems might change under global change scenarios.
Introduction of a new teaching concept for dentin post preparation with 3D printed teeth
Authors: Höhne Christian , Dickhaut Nora , Schmitter Marc
Published: March 2020

Introduction

The preparation for dentin posts is difficult and hard to learn. There are currently no reproducible simulation models to train this clinical procedure. The purpose of this study was the design, feasibility and evaluation of a three‐dimensional (3D) printed tooth model for the pre‐clinical teaching of students.

Materials and methods

A printable tooth was designed and printed by a stereolithographic printer. A total of 48 fourth‐year dental students in the first clinical course in prosthodontics were trained in a voluntary hands‐on course on 4 similar printed teeth. The students used standard model teeth and real‐teeth models during their education. They had experience in caries removement and root canal treatment on real patients. Root perforations were counted for every attempt. The different benefits of the 3D printed tooth were evaluated by a questionnaire using German school grades from 1 (best) to 6 (worst).

Results

The overall rating of the printed tooth was Ø1.9 ± 0.3. The item “suitable exercise option” was rated Ø2.0 ± 0.8, and the teeth were “easy to use” Ø1.9 ± 0.9. The item “realistic approach to dentin post preparation” was rated Ø2.1 ± 0.8, and the teeth showed the “shortcomings at a root perforation” Ø1.5 ± 0.6. The students reported to have much more motivation and enthusiasm to improve their skills with the printed teeth Ø2.1 ± 0.9. They had a strong desire to include these teeth in their pre‐clinical education before the first patient treatment Ø1.6 ± 0.8. The success rate of the dentin post preparation was significantly better for the second 25% (P = .047) and fourth 48% (P = .04) attempt.

Conclusions

The feasibility of this teaching concept was confirmed. The students had the possibility to learn a correct dentin post preparation on a printed tooth model. The learning effect with this tooth model was rated as good to very good by the questionnaire.
Cellular immune response to acute exercise: Comparison of endurance and resistance exercise
Authors: Schlagheck Marit Lea , Walzik David , Joisten Niklas , Koliamitra Christina , Hardt Luca , Metcalfe Alan J. , Wahl Patrick , Bloch Wilhelm , Schenk Alexander , Zimmer Philipp
Published: March 2020

Objectives

Exercise‐induced cellular mobilization might play a role in treatment and prevention of several diseases. However, little is known about the impact of different exercise modalities on immune cell mobilization and clinical cellular inflammation markers. Therefore, the present study aimed to investigate differences between acute endurance exercise (EE) and resistance exercise (RE) on cellular immune alterations.

Methods

Twenty‐four healthy men conducted an acute EE (cycling at 60% of peak power output) and RE (five exercise machines at 70% of the one‐repetition maximum) session lasting 50 minutes in randomized order. Blood samples were collected before, after and one hour after exercise cessation. Outcomes included counts and proportions of leukocytes, neutrophils (NEUT), lymphocytes (LYM), LYM subsets, CD4/CD8 ratio, and the clinical cellular inflammation markers NEUT/LYM ratio (NLR), platelets/LYM ratio (PLR), and systemic immune inflammation index (SII).

Results

Alterations in all outcomes were revealed except for CD8+T cells, CD4/CD8 ratio, NLR, and PLR. EE induced a stronger cellular immune response and provoked alterations in more immune cell populations than RE. SII was altered only after EE.

Conclusion

An acute EE session causes a stronger mobilization of immune cells than RE. Additionally, SII represents an integrative marker to depict immunological alterations.
Contrasting effects of different pH‐raising materials on N2O emissions in acidic upland soils
Authors: Cheng Yi , Zhang Huimin , Chen Zhaoxiong , Wang Jing , Cai Zejiang , Sun Nan , Wang Shenqiang , Zhang Jinbo , Chang Scott X. , Xu Minggang , Cai Zucong , Müller Christoph
Published: March 2020

Acidic soils, occupying ca. 40% of the world's arable soils, often need to be managed (e.g., to raise their pH and to improve crop productivity); however, the environmental impact of raising soil pH is often difficult to assess. Increasing soil pH stimulates the reduction of N2O to N2, thus lowering N2O emissions associated with denitrification, but can also increase autotrophic nitrification rates and related N2O emission. Using a 15N tracing technique, we provide process‐based insights into the effects of two acid‐neutralizing materials (quicklime [CaO] vs. pig manure) on N2O emissions in an acidified upland soil that had experienced excessive N application. Without pH adjustments we found that N2O emissions, stimulated by supply of reactive N, were related to denitrification‐ and heterotrophic nitrification‐derived N2O emissions, whereas autotrophic nitrification‐derived N2O emissions declined with decreasing soil pH. These effects were reversed by increasing soil pH via liming. However, increasing the soil pH via application of pig manure significantly increased soil N2O emissions from both nitrification and denitrification. Our study highlights that pH‐amelioration practices may enhance N2O emissions depending on the type of material applied to the soil. Therefore, both pH remediation and greenhouse gas mitigation options need to be considered together to avoid adverse environmental effects. The effect of different acid‐neutralizing materials on soil N2O emissions should be incorporated into ecosystem models to better estimate global N2O emissions when pH amelioration is practised.

Highlights

Enhanced N2O emission by N input was from denitrification and heterotrophic nitrification.

Chemical N input and liming have reversible effects on N2O emission.

Soil N2O emission was decreased by liming but increased by animal manure input.

Careful consideration of pH raising substrates is needed to avoid adverse effects.
A medieval hillfort as an island of extraordinary fertile Archaeological Dark Earth soil in the Czech Republic
Authors: Asare Michael O. , Horák Jan , Šmejda Ladislav , Janovský Martin , Hejcman Michal
Published: March 2020

Archaeological Dark Earth soil is a category of archaeological anthrosols that has gained much attention because it exhibits higher nutrient content and organic matter stocks and a characteristic dark colour, and enables higher crop yields in comparison to neighbouring soil. However, much is unknown about the chemical properties of Archaeological Dark Earth soils in Central Europe. Therefore, we studied a European Dark Earth (EDE) soil, a type of Archaeological Dark Earth soil, in the territory of the early medieval Dřevíč hillfort, Czech Republic, aiming to compare the chemical properties of EDE with a control soil unaffected by settlement activities. The black colour of EDE soil contrasted highly with the light grey Cambisol of the control. Soil reaction and total element contents (N, P, Ca, Mn, Fe, Al, Cu, Zn, Sr and Rb) were substantially larger in the EDE soil compared with the control and vice versa in the case of the C/N ratio. Also, the content of plant‐available (Mehlich III) P, Ca, K and Mg was larger in the EDE soil than the control. In contrast to Ca, plant‐available and total P and K were not well correlated. Total element contents are highly suitable for geoarchaeological purposes as enrichment factors can be easily calculated. The increased contents of these elements, together with pieces of charcoal visible in the EDE soil, indicate the deposition of organic waste and biomass ash during the existence of the hillfort. Thus, medieval hillforts can represent extraordinary nutrient‐rich islands in the cultural landscape of Central Europe. The chemical signatures generated by past settlement activities are so intense that they cannot easily be masked by short‐term intensive application of mineral fertilizers.

Highlights

Settlement activities increased soil pH and the content of anthropogenic elements.

Enrichment by P, Ca, Mn, Fe, Al, Zn, Cu, Sr and Rb may indicate settlement activities.

Analysis of total element contents is suitable for geoarchaeological purposes.

Application of mineral fertilizers cannot easily mask signatures of medieval settlement activities.
Baseline factors associated with early and late death in intracerebral haemorrhage survivors
Authors: Banerjee G. , Ambler G. , Wilson D. , Hostettler I. C. , Shakeshaft C. , Lunawat S. , Cohen H. , Yousry T. , Al‐Shahi Salman R. , Lip G. Y. H. , Houlden H. , Muir K. W. , Brown M. M. , Jäger H. R. , Werring D. J. ,   the CROMIS‐2 collaborators
Published: March 2020

Background and purpose

The aim of this study was to determine whether early and late death are associated with different baseline factors in intracerebral haemorrhage (ICH) survivors.

Methods

This was a secondary analysis of the multicentre prospective observational CROMIS‐2 ICH study. Death was defined as ‘early’ if occurring within 6 months of study entry and ‘late’ if occurring after this time point.

Results

In our cohort (n = 1094), there were 306 deaths (per 100 patient‐years: absolute event rate, 11.7; 95% confidence intervals, 10.5–13.1); 156 were ‘early’ and 150 ‘late’. In multivariable analyses, early death was independently associated with age [per year increase; hazard ratio (HR), 1.05, P = 0.003], history of hypertension (HR, 1.89, P = 0.038), pre‐event modified Rankin scale score (per point increase; HR, 1.41, P < 0.0001), admission National Institutes of Health Stroke Scale score (per point increase; HR, 1.11, P < 0.0001) and haemorrhage volume >60 mL (HR, 4.08, P < 0.0001). Late death showed independent associations with age (per year increase; HR, 1.04, P = 0.003), pre‐event modified Rankin scale score (per point increase; HR, 1.42, P = 0.001), prior anticoagulant use (HR, 2.13, P = 0.028) and the presence of intraventricular extension (HR, 1.73, P = 0.033) in multivariable analyses. In further analyses where time was treated as continuous (rather than dichotomized), the HR of previous cerebral ischaemic events increased with time, whereas HRs for Glasgow Coma Scale score, National Institutes of Health Stroke Scale score and ICH volume decreased over time.

Conclusions

We provide new evidence that not all baseline factors associated with early mortality after ICH are associated with mortality after 6 months and that the effects of baseline variables change over time. Our findings could help design better prognostic scores for later death after ICH.