bluuebunny/crossref_metadata_2025 huggingface dataset:
Balancing selection of the Intracellular Pathogen Response in natural Caenorhabditis elegans populations
Authors: van Sluijs Lisa , Bosman Kobus J. , Pankok Frederik , Blokhina Tatiana , Wilten Jop I. H. A. , Riksen Joost A. G. , Snoek Basten L. , Pijlman Gorben P. , Kammenga Jan E. , Sterken Mark G.
Published: March 2019

Genetic variation in host populations may lead to differential viral susceptibilities. Here, we investigate the role of natural genetic variation in the Intracellular Pathogen Response (IPR), an important antiviral pathway in the model organism Caenorhabditis elegans against Orsay virus (OrV). The IPR involves transcriptional activity of 80 genes including the pals-genes. We examine the genetic variation in the pals-family for traces of selection and explore the molecular and phenotypic effects of having distinct pals-gene alleles. Genetic analysis of 330 global C. elegans strains reveals that genetic diversity within the IPR-related pals-genes can be categorized in a few haplotypes worldwide. Importantly, two key IPR regulators, pals-22 and pals-25, are in a genomic region carrying signatures of balancing selection, suggesting that different evolutionary strategies exist in IPR regulation. We infected eleven C. elegans strains that represent three distinct pals-22 pals-25 haplotypes with Orsay virus to determine their susceptibility. For two of these strains, N2 and CB4856, the transcriptional response to infection was also measured. The results indicate that pals-22 pals-25 haplotype shapes the defense against OrV and host genetic variation can result in constitutive activation of IPR genes. Our work presents evidence for balancing genetic selection of immunity genes in C. elegans and provides a novel perspective on the functional diversity that can develop within a main antiviral response in natural host populations.
Jomon genome sheds light on East Asian population history
Authors: Gakuhari Takashi , Nakagome Shigeki , Rasmussen Simon , Allentoft Morten , Sato Takehiro , Korneliussen Thorfinn , Chuinneagáin Blánaid Ní , Matsumae Hiromi , Koganebuchi Kae , Schmidt Ryan , Mizushima Souichiro , Kondo Osamu , Shigehara Nobuo , Yoneda Minoru , Kimura Ryosuke , Ishida Hajime , Masuyama Yoshiyuki , Yamada Yasuhiro , Tajima Atsushi , Shibata Hiroki , Toyoda Atsushi , Tsurumoto Toshiyuki , Wakebe Tetsuaki , Shitara Hiromi , Hanihara Tsunehiko , Willerslev Eske , Sikora Martin , Oota Hiroki
Published: March 2019

Anatomical modern humans reached East Asia by >40,000 years ago (kya). However, key questions still remain elusive with regard to the route(s) and the number of wave(s) in the dispersal into East Eurasia. Ancient genomes at the edge of East Eurasia may shed light on the detail picture of peopling to East Eurasia. Here, we analyze the whole-genome sequence of a 2.5 kya individual (IK002) characterized with a typical Jomon culture that started in the Japanese archipelago >16 kya. The phylogenetic analyses support multiple waves of migration, with IK002 forming a lineage basal to the rest of the ancient/present-day East Eurasians examined, likely to represent some of the earliest-wave migrants who went north toward East Asia from Southeast Asia. Furthermore, IK002 has the extra genetic affinity with the indigenous Taiwan aborigines, which may support a coastal route of the Jomon-ancestry migration from Southeast Asia to the Japanese archipelago. This study highlight the power of ancient genomics with the isolated population to provide new insights into complex history in East Eurasia.
Live detection of neural stem and glioblastoma cells by an oligothiophene derivative
Authors: Ilkhanizadeh Shirin , Gracias Aileen , Åslund Andreas K.O. , Bäck Marcus , Simon Rozalyn , Rraklli Vilma , Migliori Bianca , Kavanagh Edel , Nelander Sven , Westermark Bengt , Uhrbom Lene , Forsberg-Nilsson Karin , Teixeira Ana I. , Konradsson Peter , Uhlén Per , Joseph Bertrand , Hermanson Ola , Nilsson K. Peter R.
Published: March 2019

Here we report a luminescent conjugated oligothiophene (LCO), named p-HTMI, for non-invasive and non-amplified real-time detection of live human patient-derived glioblastoma (GBM) cells and embryonic neural stem cells (NSCs). While p-HTMI stained only a small fraction of other cell types investigated, the mere addition of p-HTMI to the cell culture resulted in efficient detection of NSCs or GBM cells from rodents and humans within minutes. p-HTMI is functionalized with a methylated imidazole moiety resembling the side chain of histidine/histamine, and non-methylated analogues were not functional. p-HTMI were readily able to detect a subpopulation of human cells in vivo in mouse brain sections with tumors developed from orthotopically transplanted patient-derived GBM cells. Cell sorting experiments of human GBM cells demonstrated that p-HTMI labeled the same population as CD271, a proposed marker for stem cell-like cells and rapidly migrating cells in glioblastoma. Our results suggest that the LCO p-HTMI is a versatile tool for immediate and selective detection of subpopulations of neural stem and glioma cells.
Neuronal programming by microbiota enables environmental regulation of intestinal motility
Authors: Obata Yuuki , Boeing Stefan , Castaño Álvaro , Bon-Frauches Ana Carina , Gomez de Agüero Mercedes , Boesmans Werend , Yilmaz Bahtiyar , Lopes Rita , Huseynova Almaz , Maradana Muralidhara Rao , Vanden Berghe Pieter , Murray Andrew J. , Stockinger Brigitta , Macpherson Andrew J. , Pachnis Vassilis
Published: March 2019

Environmental signals modulate the activity of the nervous system and harmonize its output with the outside world. Synaptic activity is crucial for integrating sensory and effector neural pathways but the role of transcriptional mechanisms as environmental sensors in the nervous system remains unclear. By combining a novel strategy for transcriptomic profiling of enteric neurons with microbiota manipulation, we demonstrate that the transcriptional programs of intestinal neural circuits depend on their anatomical and physiological context. We also identify the ligand-dependent transcription factor Aryl hydrocarbon Receptor (AhR) is an intrinsic regulator of enteric nervous system output. AhR is instated as a neuronal biosensor in response to microbiota colonization allowing resident enteric neurons to directly monitor and respond to the intestinal microenvironment. We suggest that AhR signaling integrates neuronal activity with host defence mechanisms towards gut homeostasis and health.

One Sentence Summary

Microbiota induce expression of AhR in enteric neurons of the distal intestine enabling them to respond to environmental signals.
Recombinant spider silk protein matrices facilitate multi-analysis of calcium-signaling in neural stem cell-derived AMPA-responsive neurons
Authors: Lewicka Michalina , Rebellato Paola , Lewicki Jakub , Uhlén Per , Rising Anna , Hermanson Ola
Published: March 2019

Neural progenitors or stem cells (NSCs) show great promise in drug discovery and clinical application. Yet few efforts have been made to optimize biocompatible materials for such cells to be expanded and used in clinical conditions. We have previously demonstrated that NSCs are readily cultured on substrates of certain recombinant spider silk protein without addition of animal- or human-derived components. The question remains however whether this material allows differentiation into functional neurons and glia, and whether such differentiation can take place also when the NSCs are cultured within the material in a pseudo-3D context. Here we demonstrate that “foam”-like structures generated from recombinant spider silk protein (4RepCT) provided excellent matrices for the generation and multicellular analysis of functional excitatory neurons from NSCs without addition of animal- or human-derived components. NSCs isolated from the cerebral cortices of rat embryos were cultured on either 4RepCT matrices shaped as foam-like structures without coating, or on conventional polystyrene plates coated with poly-L-ornithine and fibronectin. Upon treatment with recombinant proteins including the growth factor BMP4 or a combination of BMP4 and the signaling factor Wnt3a, the cortical NSCs cultured in 4RepCT foam-like structures differentiated efficiently into neurons that responded to glutamate receptor agonists, such as AMPA, to at least the same extent as control cultures. Matrices derived from recombinant spider silk proteins thus provide a functional microenvironment for neural stem cells without any animal- or human-derived components, and can be employed in the development of new strategies in stem cell research and tissue engineering.
Multi-grip classification-based prosthesis control with two EMG-IMU sensors
Authors: Krasoulis Agamemnon , Vijayakumar Sethu , Nazarpour Kianoush
Published: March 2019

In the field of upper-limb myoelectric prosthesis control, the use of statistical and machine learning methods has been long proposed as a means of enabling intuitive grip selection and actuation. Recently, this paradigm has found its way toward commercial adoption. Machine learning-based prosthesis control typically relies on the use of a large number of electrodes. Here, we propose an end-to-end strategy for multi-grip, classification-based prosthesis control using only two sensors, comprising electromyography (EMG) electrodes and inertial measurement units (IMUs). We emphasize the importance of accurately estimating posterior class probabilities and rejecting predictions made with low confidence, so as to minimize the rate of unintended prosthesis activations. To that end, we propose a confidence-based error rejection strategy using grip-specific thresholds. We evaluate the efficacy of the proposed system with real-time pick and place experiments using a commercial multi-articulated prosthetic hand and involving 12 able-bodied and two transradial (i.e., below-elbow) amputee participants. Results promise the potential for deploying intuitive, classification-based multi-grip control in existing upper-limb prosthetic systems subject to small modifications.
Unbiased metagenomic sequencing for pediatric meningitis in Bangladesh reveals neuroinvasive Chikungunya virus outbreak and other unrealized pathogens
Authors: Saha Senjuti , Ramesh Akshaya , Kalantar Katrina , Malaker Roly , Hasanuzzaman Md , Khan Lillian M. , Mayday Madeline Y , Sajib M S I , Li Lucy M. , Langelier Charles , Rahman Hafizur , Crawford Emily D. , Tato Cristina M. , Islam Maksuda , Juan Yun-Fang , Bourcy Charles de , Dimitrov Boris , Wang James , Tang Jennifer , Sheu Jonathan , Egger Rebecca , De Carvalho Tiago Rodrigues , Wilson Michael R. , Saha Samir K , DeRisi Joseph L
Published: March 2019

The disease burden due to meningitis in low and middle-income countries remains significant and failure to determine an etiology impedes appropriate treatment for patients and evidence-based policy decisions for populations. Broad-range pathogen surveillance using metagenomic next-generation sequencing (mNGS) of RNA isolated from cerebral spinal fluid (CSF) provides an unbiased assessment for possible infectious etiologies. In this study, our objective was to use mNGS to identify etiologies of pediatric meningitis in Bangladesh.

We conducted a retrospective case-control mNGS study on CSF from patients with known neurologic infections (n=36), idiopathic meningitis (n=25), without infection (n=30) and six environmental samples collected between 2012-2018. Using an open-access, cloud-based bioinformatics pipeline (IDseq) and machine learning, we identified potential pathogens which were confirmed through qPCR and Sanger sequencing. These cases were followed-up through phone/home-visits. The CSF samples were collected from children with WHO-defined meningeal signs during prospective meningitis surveillance at the largest pediatric referral hospital in Bangladesh.

The 91 participants (42% female) ranged in age from 0-160 months (median: 9 months). In samples with known infectious causes of meningitis and without infections (n=66), there was 83% concordance between mNGS and conventional testing. In idiopathic cases (n=25), mNGS identified a potential etiology in 40% (n=10), including bacterial and viral pathogens. There were three instances of neuroinvasive Chikungunya virus (CHIKV). The CHIKV genomes were >99% identical to each other and to a Bangladeshi strain only previously recognized to cause systemic illness in 2017. CHIKV qPCR of all remaining stored CSF samples from children who presented with idiopathic meningitis in 2017 at the same hospital (n=472) revealed 17 additional CHIKV meningitis cases. Orthogonal molecular confirmation of each mNGS-identified infection, case-based clinical data, and follow-up of patients substantiated the key findings.

Using mNGS, we obtained a microbiological diagnosis for 40% of idiopathic meningitis cases and identified a previous unappreciated pediatric CHIKV meningitis outbreak. Case-control CSF mNGS surveys can complement conventional diagnostic methods to identify etiologies of meningitis and facilitate informed policy decisions.
Sci-Hi-C: a single-cell Hi-C method for mapping 3D genome organization in large number of single cells
Authors: Ramani Vijay , Deng Xinxian , Qiu Ruolan , Lee Choli , Disteche Christine M , Noble William S , Duan Zhijun , Shendure Jay
Published: March 2019

The highly dynamic nature of chromosome conformation and three-dimensional (3D) genome organization leads to cell-to-cell variability in chromatin interactions within a cell population, even if the cells of the population appear to be functionally homogeneous. Hence, although Hi-C is a powerful tool for mapping 3D genome organization, this heterogeneity of chromosome higher order structure among individual cells limits the interpretive power of population based bulk Hi-C assays. Moreover, single-cell studies have the potential to enable the identification and characterization of rare cell populations or cell subtypes in a heterogeneous population. However, it may require surveying relatively large numbers of single cells to achieve statistically meaningful observations in single-cell studies. By applying combinatorial cellular indexing to chromosome conformation capture, we developed single-cell combinatorial indexed Hi-C (sci-Hi-C), a high throughput method that enables mapping chromatin interactomes in large number of single cells. We demonstrated the use of sci-Hi-C data to separate cells by karytoypic and cell-cycle state differences and to identify cellular variability in mammalian chromosomal conformation. Here, we provide a detailed description of method design and step-by-step working protocols for sci-Hi-C.
Simple Framework for Constructing Functional Spiking Recurrent Neural Networks
Authors: Kim Robert , Li Yinghao , Sejnowski Terrence J.
Published: March 2019

Cortical microcircuits exhibit complex recurrent architectures that possess dynamically rich properties. The neurons that make up these microcircuits communicate mainly via discrete spikes, and it is not clear how spikes give rise to dynamics that can be used to perform computationally challenging tasks. In contrast, continuous models of rate-coding neurons can be trained to perform complex tasks. Here, we present a simple framework to construct biologically realistic spiking recurrent neural networks (RNNs) capable of learning a wide range of tasks. Our framework involves training a continuous-variable rate RNN with important biophysical constraints and transferring the learned dynamics and constraints to a spiking RNN in a one-to-one manner. The proposed framework introduces only one additional parameter to establish the equivalence between rate and spiking RNN models. We also study other model parameters related to the rate and spiking networks to optimize the one-to-one mapping. By establishing a close relationship between rate and spiking models, we demonstrate that spiking RNNs could be constructed to achieve similar performance as their counterpart continuous rate networks.
Epistatic Networks Associated with Parent-of-Origin Effects on Metabolic Traits
Authors: Macias-Velasco Juan F , Pierre Celine L. St. , Wayhart Jessica P , Yin Li , Spears Larry , Miranda Mario A. , Funai Katsuhiko , Cheverud James M , Semenkovich Clay F , Lawson Heather A
Published: March 2019

Parent-of-origin effects (POE) are unexpectedly common in complex traits, including metabolic and neurological diseases. POE can also be modified by the environment, but the architecture of these gene-by-environmental effects on phenotypes remains to be unraveled. Previously, quantitative trait loci (QTL) showing context-specific POE on metabolic traits were mapped in the F16 generation of an advanced intercross between LG/J and SM/J inbred mice. However, these QTL were not enriched for known imprinted genes, suggesting another mechanism is needed to explain these POE phenomena. Here, we use a simple yet powerful F1 reciprocal cross model to test the hypothesis that non-imprinted genes can generate complex POE on metabolic traits through genetic interactions with imprinted genes. Male and female mice from a F1 reciprocal cross of LG/J and SM/J strains were fed either high or low fat diets. We generated expression profiles from three metabolically-relevant tissues: hypothalamus, white adipose, and liver. We identified two classes of parent-of-origin expression biases: genes showing parent-of-origin-dependent allele-specific expression and biallelic genes that are differentially expressed by reciprocal cross. POE patterns of both gene classes are highly tissue-and context-specific, sometimes occurring only in one sex and/or diet cohort in a particular tissue. We then constructed tissue-specific interaction networks among genes from these two classes of POE. A key subset of gene pairs show significant epistasis in the F16 LG/J x SM/J advanced intercross data in cases where the biallelic gene fell within a previously-identified metabolic POE QTL interval. We highlight one such interaction in adipose, between Nnat and Mogat1, which associates with POE on multiple adiposity traits. Both genes localize to the endoplasmic reticulum of adipocytes and play a role in adipogenesis. Additionally, expression of both genes is significantly correlated in human visceral adipose tissue. The genes and networks we present here represent a set of actionable interacting candidates that can be probed to further identify the machinery driving POE on complex traits.
ESCRT-III/Vps4 controls heterochromatin-nuclear envelope attachments
Authors: Pieper Gerard H. , Sprenger Simon , Teis David , Oliferenko Snezhana
Published: March 2019

In eukaryotes chromosomes are compartmentalized within the nucleus delimited by the double membrane of the nuclear envelope (NE). Defects in the function and structure of the NE are linked to disease1,2. During interphase, the NE organizes the genome and regulates its expression3. As cells enter mitosis, chromosomes are released from the NE, which is then remodelled to form the daughter nuclei at mitotic exit4. Interactions between the NE and chromatin underpinning both interphase and post-mitotic NE functions are executed by inner nuclear membrane (INM) proteins such as members of the evolutionarily conserved chromatin-binding LEM-domain family5–8. How chromatin tethering by these transmembrane proteins is controlled in interphase and if such a regulation contributes to subsequent NE dynamics in mitosis remains unclear. Here we probe these fundamental questions using an emerging model organism, the fission yeastSchizosaccharomyces japonicus, which breaks and reforms the NE during mitosis9,10. We show that attachments between heterochromatin and the transmembrane Lem2-Nur1 complex are continuously remodelled in interphase by the ESCRT-III/AAA-ATPase Vps4 machinery. ESCRT-III/Vps4 mediates the release of Lem2-Nur1 from heterochromatin as a prerequisite for the timely progression through mitosis. Failure in this process leads to persistent association of chromosomes with the INM, which prevents Lem2-Nur1 from re-localizing to the sites of NE sealing around the mitotic spindle and severely delays re-establishment of nucleocytoplasmic compartmentalization. Our work establishes the INM transmembrane Lem2-Nur1 complex as a ‘substrate’ for ESCRT-III/Vps4 to couple dynamic tethering of chromosomes to the INM with the establishment of nuclear compartmentalization.
Multivariate Analysis Illuminates the Effects of Vacuum Drying on the Extractable and Nonextractable Polyphenols Profile of Loquat Fruit
Authors: Li Wenfeng , Wang Xv , Zhang Jing , Zhao Xin , Wu Yingmei , Tan Si , Zheng Qiaoran , Gao Xiaoxv
Published: March 2019

The current study evaluated the effects of vacuum drying on the whole polyphenol profile of loquat fruit, including extractive and nonextractive polyphenols. Absorbance analysis determined that total polyphenol content and antioxidant levels were higher in loquat fruit vacuum dried at 140 °C than in loquat fruit vacuum dried at 70 °C. The results of ultra‐HPLC–triple quadruple mass spectrum analysis showed that 15 phenolic acids and 17 flavonoids were found in dried loquat fruit. Multivariate integrative (MINT) sparse partial least square‐discriminant analysis showed that vacuum drying affects the polyphenol profile of loquat fruit. Co‐analysis of principal component analysis, partial least square‐discriminant analysis, and orthometric partial least square‐discriminant analysis revealed that vacuum drying mainly changed the content of chlorogenic acid, cryptochlorogenic acid, protocatechuic acid, phloretin, and hesperidin in loquat fruit. Chlorogenic acid (12.020 to 39.153 µg/g d.b. [dried base weight]), the main polyphenol in dried loquat fruit, was degraded to caffeic acid (0.028 to 2.365 µg/g d.b.) and protocatechuic acid (0.014 to 18.285 µg/g d.b.) during vacuum drying. Moreover, vacuum drying also induced the isomerization of chlorogenic acid into cryptochlorogenic acid (1.628 to 12.737 µg/g d.b.). These results might be used to develop dried loquat fruit with high levels of polyphenols and antioxidant activity.

Practical Application

Interests in polyphenols of loquat fruit had increased greatly because of their possible role in health benefits. This work provided a holistic insight in the effects of vacuum drying on polyphenols profile of loquat fruit. Current results have contributed to the development of vacuum‐drying method, which produced loquat fruit rich in polyphenols. Furthermore, it also suggested that multivariate analysis was a feasible method to reveal the important changes of polyphenols profile during food processing.
V.PhyloMaker: an R package that can generate very large phylogenies for vascular plants
Authors: Jin Yi , Qian Hong
Published: March 2019

We present V.PhyloMaker, a freely available package for R designed to generate phylogenies for vascular plants. The mega‐tree implemented in V.PhyloMaker (i.e. GBOTB.extended.tre), which was derived from two recently published mega‐trees and includes 74 533 species and all families of extant vascular plants, is the largest dated phylogeny for vascular plants. V.PhyloMaker can generate phylogenies for very large species lists (the largest species list that we tested included 314 686 species). V.PhyloMaker generates phylogenies at a fast speed, much faster than other phylogeny‐generating packages. Our tests of V.PhyloMaker show that generating a phylogeny for 60 000 species requires less than six hours. V.PhyloMaker includes an approach to attach genera or species to their close relatives in a phylogeny. We provide a simple example in this paper to show how to use V.PhyloMaker to generate phylogenies.
Noise‐induced reduction in the attack rate of a planktivorous freshwater fish revealed by functional response analysis
Authors: Hanache Priscillia , Spataro Thierry , Firmat Cyril , Boyer Nicolas , Fonseca Paulo , Médoc Vincent
Published: March 2019

Anthropogenic noise can affect animals physically, physiologically, and behaviourally. Although individual responses to noise are well documented, the consequences in terms of community structure, species coexistence, and ecosystem functioning remain fairly unknown.

The impact of noise on predation has received a growing interest and alterations in trophic links are observed when animals shift from foraging to stress‐related behaviours, are distracted by noise, or because of acoustic masking. However, the experimental procedures classically used to quantify predation do not inform on the potential demographic impact on prey.

We derived the relationship between resource use and availability (the functional response) for European minnows (Phoxinus phoxinus) feeding on dipteran larvae (Chaoborussp.) under two noise conditions: ambient noise and ambient noise supplemented with motorboat noise. The shape and magnitude of the functional response are powerful indicators of population outcomes and predator–prey dynamics. We also recorded fish behaviour to explore some proximate determinants of altered predation.

For both noise conditions, fish displayed a saturating (typeII) functional response whose shape depends on two parameters: attack rate and handling time. Boat noise did not affect handling time but significantly reduced attack rate, resulting in a functional response curve of the same height but with a less steep initial slope. Fish exhibited a stress‐related response to noise including increased swimming distance, more social interactions, and altered spatial distribution.

Our study shows the usefulness of the functional response approach to study the ecological impacts of noise and illustrates how the behavioural responses of predators to noise can modify the demographic pressure on prey. It also suggests that prey availability might mediate the negative effect of noise on predation. Community outcomes are expected if the reduced consumption of the main food sources goes with the overconsumption of alternative food sources, changing the distribution pattern of interaction strengths. Predation release could also trigger a trophic cascade, propagating the effect of noise to lower trophic levels.
Spatial and seasonal variability in the trophic role of aquatic insects: An assessment of functional feeding group applicability
Authors: Tierno de Figueroa José Manuel , López‐Rodríguez Manuel Jesús , Villar‐Argaiz Manuel
Published: March 2019

Functional feeding groups (FFGs) have been used over recent decades to classify aquatic insects according to their trophic resources and the mechanisms used to acquire them. Nonetheless, the classification of a taxon into anFFGis often based on its membership of a genus or family rather than on species level information. This extrapolation of theFFGmembership of one taxon to the remaining taxa within a group has led to misconceptions and erroneous conclusions.

This study aimed to determine the amount of variation inFFGmembership within species among seasons and locations and whether this was related to resource availability. For this purpose, we sampled over two seasons (autumn and spring) at three altitudes in each of four basins, measuring the main trophic resources available for aquatic insects and collecting representatives of taxa traditionally assigned to each of the mainFFGs. Based on analyses of the diet of multiple individuals in each location and season, we calculated the percentage belonging to eachFFG.

Diets differed widely among taxa, and within taxa they often varied significantly between sites in the same season and at the same site between different seasons. Species' diets could also differ between different river basins when specimens were collected at the same altitude and season. In some cases, although the primary food source remained the same, the contribution from a secondary source varied between sites. Although availability of the three main trophic resources (epilithic algae,fineand coarseparticulate organic matter) differed among sites, we found no association overall between the availability of these resources and insect diets.

Our results agree with several recent studies that show that the diets of stream invertebrates vary widely in space and time, potentially indicative of widespread omnivory/opportunistic feeding. This makes classifying taxa into particularFFGs without collection of dietary data, or by assigning oneFFGto a taxon across all places and times, fraught with potential errors. These have possible repercussions for ecological studies related to matter cycles or food webs, amongst other issues. Some stream insects are consistently predaceous or have piercing mouthparts that constrain their diet. However, it appears increasingly likely that the majority of taxa, formerly labelled as scraper, shredder, and collector–gatherer or filterer, should be regarded as feeding on a range of sources and not routinely assigned into distinctFFGs (in the absence of local dietary data). We suggest researchers classify stream insect taxa as omnivores unless there are local data that show otherwise, or the taxa are obligate predators, feed by piercing or are otherwise physiologically constrained to a particular diet.
Oral health‐related quality of life and satisfaction of edentulous patients using conventional complete dentures and implant‐retained overdentures: An umbrella systematic review
Authors: Sharka Rayan , Abed Hassan , Hector Mark
Published: March 2019

Background

Loss of teeth has a negative influence on essential oral functions. It is important to understand edentulous patients’ perceptions about the impacts of treatment options on their oral health‐related quality of life (OHRQoL) and satisfaction.

Aims

To appraise the systematic reviews (with/without meta‐analysis) that investigate the impacts of complete conventional dentures (CCDs) and/or implant‐retained overdentures (IRODs) on the oral health‐related quality of life (OHRQoL) and satisfaction among edentulous patients.

Methods

The Joanna Briggs Institute (JBI) methodology for conduct of an umbrella systematic review was followed. Three database systems were used: Medline, Google Scholar and Cochrane Library. PROSPERO was searched for ongoing or recently completed systematic reviews. The reviews must report OHRQoL and patients’ satisfaction as outcomes.

Results

A total of eight reviews were included in data synthesis (six were systematic reviews without meta‐analysis, one was systematic review with meta‐analysis, and one was meta‐analysis). The level of evidence of all included reviews based on the Scottish Intercollegiate Guidelines Network ranged between 1+ and 1−.

Conclusion

The results of this umbrella systematic review demonstrate the superiority of using IRODs compared with CCDs on the OHRQoL and patients’ satisfaction outcomes. However, this positive impact is more accentuated when patients demand implant treatment or cannot adapt to CCDs treatment. Financial factors and adaptive capability indeed affect patient tolerance to both treatment modalities.
Mortality of patients with haemophilia in Brazil: First report
Authors: Jardim Leticia Lemos , van der Bom Johanna G. , Caram‐Deelder Camila , Gouw Samantha Claudia , Leal Cherchiglia Mariangela , Rezende Suely Meireles
Published: March 2019

Introduction

Brazil has the fourth largest world population of patients with haemophilia. However, mortality rates in this population are unknown.

Aim

To analyse mortality and its causes in Brazilian patients with haemophilia from 2000 to 2014.

Methods

The number of deceased patients with haemophilia and causes of death were obtained from the Brazilian National Mortality Information System (SIM), according to the 10th International Classification of Diseases (ICD‐10). Standardized mortality ratios (SMR) were calculated to estimate the rate of overall death of patients with haemophilia relative to that of the Brazilian general male population.

Results

A total of 784 deaths were identified in the period of 15 years. Mortality of patients with haemophilia was 13% higher when compared with the general male population (SMR 1.13, 95% CI: 1.01‐1.16). Haemorrhage was the main cause of death (n = 254; 32.4%) of which 137 (54%) was intracranial haemorrhage. The total number of deaths due to HIV decreased over the years, and an increase in deaths due to cancer and cardiovascular disease was observed. A total of 129 deaths (16.5%) were related to hepatitis infection, of whom, 109 (86.5%) patients also presented with cirrhosis and hepatocellular carcinoma or other liver diseases.

Conclusion

Mortality rate of Brazilian patients with haemophilia decreased over the evaluated period. Intracranial haemorrhage is still an important cause of death in these patients, which requires major effort for prevention. Death due to age‐related cardiovascular disease and cancer has increased over the years, following the same tendency observed in developed countries.
The peripheral differentiation of human natural killer T cells
Authors: Liu Jie , Hill Brenna J , Darko Sam , Song Kaimei , Quigley Máire F , Asher Tedi E , Morita Yohei , Greenaway Hui Y , Venturi Vanessa , Douek Daniel C , Davenport Miles P , Price David A , Roederer Mario
Published: March 2019

The peripheral maturation of human CD1d‐restricted natural killer T (NKT) cells has not been well described. In this study, we identified four major subsets of NKT cells in adults, distinguished by the expression of CD4, CD8 and CCR5. Phenotypic analysis suggested a hierarchical pattern of differentiation, whereby immature CD4+CD8−CCR5− cells progressed to an intermediate CD4+CD8−CCR5+ stage, which remained less differentiated than the CD4−CD8− and CD4−CD8+ subsets, both of which expressed CCR5. This interpretation was supported by functional data, including clonogenic potential and cytokine secretion profiles, as well as T‐cell receptor (TCR) excision circle analysis. Moreover, conventional and high‐throughput sequencing of the corresponding TCR repertoires demonstrated significant clonotypic overlap within individuals, especially between the more differentiated CD4−CD8− and CD4−CD8+ subsets. Collectively, these results mapped a linear differentiation pathway across the post‐thymic landscape of human CD1d‐restricted NKT cells.
Assessing the efficacy of new biologic therapies in hidradenitis suppurativa: consistency vs. bias in outcome measures in moderate and severe disease
Authors: Frew J.W.
Published: March 2019

Linked article: M. Kovacs et al. J Eur Acad Dermatol Venereol 2019; 33: e300. https://doi.org/10.1111/jdv.15573
Visual Abstracts to Disseminate Geriatrics Research Through Social Media
Authors: Lindquist Lee A. , Ramirez‐Zohfeld Vanessa
Published: March 2019

Dissemination of cutting‐edge geriatrics‐focused research is essential for academic geriatrics researchers, clinicians, and older adults and their caregivers. Social media channels, such as Twitter, provide a means of quickly reaching a wide array of users, globally. Besides standard tweets with links to research articles, visual abstracts are a means of delivering research results visually to end users succinctly. We compared the use of a standard tweet with a linked article with a tweet that held an added visual abstract, for a recent Journal of the American Geriatrics Society article. While the standard tweet received 24 984 impressions with 17 retweets and 36 likes over 8 days, the visual abstract inclusive tweet received 168 447 impressions with 81 retweets and 100 likes in 4 days. To assist researchers on future visual abstract development, we provide a framework and real‐world guide on translation of research abstracts into visual abstracts. We hope that by providing evidence and the means to create visual abstracts, researchers in geriatrics may be empowered to disseminate their research through this method and potentially advance the care of older adults worldwide.
Making and Measuring an Impact in a Digital World: The Role of Social Media and the Medical Journal
Authors: Widera Eric , Trucil Daniel E. , Smith Alexander K.
Published: March 2019

This editorial comments on the article by Lindquist et al in this issue.
Cell senescence, apoptosis and DNA damage cooperate in the remodeling processes accounting for heart morphogenesis
Authors: Lorda‐Diez Carlos I. , Solis‐Mancilla Michelle E. , Sanchez‐Fernandez Cristina , Garcia‐Porrero Juan A. , Hurle Juan M. , Montero Juan A.
Published: March 2019

During embryonic development, organ morphogenesis requires major tissue rearrangements that are tightly regulated at the genetic level. A large number of studies performed in recent decades assigned a central role to programmed cell death for such morphogenetic tissue rearrangements that often sculpt the shape of embryonic organs. However, accumulating evidence indicates that far from being the only factor responsible for sculpting organ morphology, programmed cell death is accompanied by other tissue remodeling events that ensure the outcome of morphogenesis. In this regard, cell senescence has been recently associated with morphogenetic degenerative embryonic processes as an early tissue remodeling event in development of the limbs, kidney and inner ear. Here, we have explored cell senescence by monitoring β‐galactosidase activity during embryonic heart development where programmed cell death is believed to exert an important morphogenetic function. We report the occurrence of extensive cell senescence foci during heart morphogenesis. These foci overlap spatially and temporally with the areas of programmed cell death that are associated with remodeling of the outflow tract to build the roots of the great arteries and with the septation of cardiac cavities. qPCR analysis allowed us to identify a gene expression profile characteristic of the so‐called senescence secretory associated phenotype in the remodeling outflow tract of the embryonic heart. In addition, we confirmed local upregulation of numerous tumor suppressor genes including p21, p53, p63, p73 and Btg2. Interestingly, the areas of cell senescence were also accompanied by intense lysosomal activation and non‐apoptotic DNA damage revealed by γH2AX immunolabeling. Considering the importance of sustained DNA damage as a triggering factor for cell senescence and apoptosis, we propose the coordinated contribution of DNA damage, senescence and apoptotic cell death to assure tissue remodeling in the developing vertebrate heart.
Bryophytes in fir waves: Forest canopy indicator species and functional diversity decline in canopy gaps
Authors: Berdugo Monica B. , Dovciak Martin
Published: March 2019

Aims

Bryophytes can cover three quarters of the ground surface, play key ecological functions, and increase biodiversity in mesic high‐elevation conifer forests of the temperate zone. Forest gaps affect species coexistence (and ecosystem functions) as suggested by the gap and gap‐size partitioning hypotheses (GPH, GSPH). Here we test these hypotheses in the context of high‐elevation forest bryophyte communities and their functional attributes.

Study Site

Spruce–fir forests on Whiteface Mountain, NY, USA.

Methods

We characterized canopy openness, microclimate, forest floor substrates, vascular vegetation cover, and moss layer (cover, common species, and functional attributes) in three canopy openness environments (gap, gap edge, forest canopy) across 20 gaps (fir waves) (n = 60); the functional attributes were based on 16 morphologic, reproductive, and ecological bryophyte plant functional traits (PFTs). We tested GPH and GSPH relative to bryophyte community metrics (cover, composition), traits, and trait functional sensitivity (functional dispersion; FDis) using indicator species analysis, ordination, and regression.

Results

Canopy openness drove gradients in ground‐level temperature, substrate abundance and heterogeneity (beta diversity), and understory vascular vegetation cover. The GPH was consistent with (a) the abundance patterns of forest canopy indicator species (Dicranum fuscescens, Hypnum imponens, and Tetraphis pellucida), and (b) FDis based on three PFTs (growth form, fertility, and acidity), both increasing with canopy cover. We did not find support for GPH in the remaining species or traits, or for GSPH in general; gap width (12–44 m) was not related to environmental or bryophyte community gradients.

Conclusions

The observed lack of variation in most bryophyte metrics across canopy environments suggests high resistance of the bryophyte layer to natural canopy gaps in high‐elevation forests. However, responses of forest canopy indicator species suggest that canopy mortality, potentially increased by changing climate or insect pests, may cause declines in some forest canopy species and consequently in the functional diversity of bryophyte communities.
Sorghum tiller bud growth is repressed by contact with the overlying leaf
Authors: Liu Ruixian , Finlayson Scott A.
Published: March 2019

Basal branching in grasses, or tillering, is an important trait determining both form and function of crops. Although similarities exist between eudicot and grass branching programs, one notable difference is that the tiller buds of grasses are covered by the subtending leaf, whereas eudicot buds are typically unconstrained. The current study shows that contact with the leaf sheath represses sorghum bud growth by providing a mechanical signal that cues the bud to refrain from rapid growth. Leaf removal resulted in massive reprogramming of the bud transcriptome that included signatures of epigenetic modifications and also implicated several hormones in the response. Bud abscisic acid transiently increased, then decreased following leaf removal relative to controls, and abscisic acid was necessary to repress bud growth in the presence of the leaf. Jasmonic acid (JA) levels and signalling increased in buds following leaf removal. Remarkably, application of JA to buds in situ promoted growth. The repression of bud growth by leaf contact shares characteristics of thigmomorphogenic responses in other systems, including the involvement of JA, though the JA effect is opposite. The repression of bud growth by leaf contact may represent a mechanism to time tillering to an appropriate developmental stage of the plant.
A simple score can identify kidney transplant recipients at high risk of severe infection over the following 2 years
Authors: Dendle Claire , Polkinghorne Kevan R. , Mulley William R. , Gan Poh‐Yi , Kanellis John , Stuart Rhonda L. , Thursky Karin , Holdsworth Stephen R.
Published: March 2019

Background

The aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients.

Methods

We conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing.

Results

Fifty‐nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67‐0.83).

Conclusion

Our level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high‐risk patients. This data can inform research that examines strategies to reduce the risks of infection.
Quantitative assessment of the anticoagulant in plasma units collected by plasmapheresis
Authors: Vurro Filippo , Merolle Lucia , Marraccini Chiara , Parisi Maura , Canovi Laura , Erta Barbara , Santachiara Annalisa , Bonvicini Laura , Giorgi Rossi Paolo , Baricchi Roberto , Pertinhez Thelma A.
Published: March 2019

BACKGROUND

To date, the quantification of the anticoagulant (ACD‐A) in plasma units has been based on theoretical calculations. An accurate quantification could help minimize the risks associated with plasmapheresis, given that the total ACD‐A used during the procedure is distributed between the donor and the plasma unit.

Our aim was to experimentally quantify the volume of ACD‐A in units collected by plasmapheresis.

STUDY DESIGN AND METHODS

We used proton nuclear magnetic resonance spectroscopy to measure the ACD‐A volume in 295 plasma units collected by the Azienda USL‐IRCCS of Reggio Emilia, Italy. We analyzed the determinants of the differences between estimated and measured ACD‐A through multivariate regression models.

RESULTS

The experimentally measured ACD‐A in plasma units was variable, with 45% of the samples showing a discrepancy of more than 15 mL compared to the manufacturer's estimate.

ACD‐A was underestimated for higher density of the units (p < 0.0005); a weak association was also observed with triglycerides (underestimated for higher levels, p = 0.015) and sex (overestimated in females, p = 0.008), but our model explained only 35% of the individual variability.

CONCLUSION

The manufacturer's algorithms do not accurately estimate the ACD‐A in units collected by plasmapheresis. Donor‐related characteristics may affect ACD‐A distribution between donor and plasma unit, thereby explaining the discrepancies between estimate and measurement.

Errors in the estimate of the ACD‐A actually received by donors could hamper studies on dose–response relationship between anticoagulant and adverse reactions. Our work should stimulate research on tailored procedures aimed at minimizing the anticoagulant received by donors and increasing plasmapheresis safety.
A standardized kodecyte method to quantify ABO antibodies in undiluted plasma of patients before ABO‐incompatible kidney transplantation
Authors: Perry Holly , Bovin Nicolai , Henry Stephen
Published: March 2019

BACKGROUND

The ABO transplantation barrier can be breached if antibody is reduced to low levels. Current serologic methods involve testing natural RBCs against dilutions of plasma to determine antibody levels, but these methods are poorly standardized and inherently error prone with consequent large inter‐ and intra laboratory variation. We evaluated the feasibility of using antigen‐standardized kodecytes and undiluted plasma as an alternative method for antibody measurement in patients preparing for ABO‐incompatible kidney transplantation.

STUDY DESIGN AND METHODS

A panel of five kodecytes, bearing defined levels of synthetic blood group A type 2 antigen was developed (kodecyte assay) to show reaction patterns against undiluted plasma that were indicative of anti‐A and anti‐A,B levels. This panel was evaluated against the contemporary method of testing dilutions of plasma against A1 cells to determine titer (A1 cell assay) in both column agglutination and tube techniques. Evaluation samples included reference standards, 102 group O plus 23 group B donors, and 40 pre‐ and post‐plasmapheresis samples from five prospective ABO‐incompatible kidney transplant patients.

RESULTS

Comparisons between the kodecyte and A1 cell assays found greater than 90% correlation for all samples. Tube and column agglutination technology platform differences were observed with A1 cells and kodecytes. Discordant samples were generally found to have high ratios of IgG:IgM or vice versa.

CONCLUSIONS

The kodecyte assay is a simple method that requires no sample dilution, and an optimized two‐cell kodecyte panel is potentially capable of informing ABO‐incompatible kidney transplantation decisions based on antibody levels.