bluuebunny/crossref_metadata_2025 huggingface dataset:
Streptococcus gordonii
programs epithelial cells to resist ZEB2 induction by
Porphyromonas gingivalis
Authors: Ohshima Jun , Wang Qian , Fitzsimonds Zackary R. , Miller Daniel P. , Sztukowska Maryta N. , Jung Young-Jung , Hayashi Mikako , Whiteley Marvin , Lamont Richard J.
Published: April 2019

The polymicrobial microbiome of the oral cavity is a direct precursor of periodontal diseases, and changes in microhabitat or shifts in microbial composition may also be linked to oral squamous cell carcinoma. Dysbiotic oral epithelial responses provoked by individual organisms, and which underlie these diseases, are widely studied. However, organisms may influence community partner species through manipulation of epithelial cell responses, an aspect of the host microbiome interaction that is poorly understood. We report here that
Porphyromonas gingivalis
, a keystone periodontal pathogen, can up-regulate expression of ZEB2, a transcription factor which controls epithelial–mesenchymal transition and inflammatory responses. ZEB2 regulation by
P. gingivalis
was mediated through pathways involving β-catenin and FOXO1. Among the community partners of
P. gingivalis
,
Streptococcus gordonii
was capable of antagonizing ZEB2 expression. Mechanistically,
S. gordonii
suppressed FOXO1 by activating the TAK1-NLK negative regulatory pathway, even in the presence of
P. gingivalis
. Collectively, these results establish
S. gordonii
as homeostatic commensal, capable of mitigating the activity of a more pathogenic organism through modulation of host signaling.
Structural basis for auxiliary subunit KCTD16 regulation of the GABA
B
receptor
Authors: Zuo Hao , Glaaser Ian , Zhao Yulin , Kurinov Igor , Mosyak Lidia , Wang Haonan , Liu Jonathan , Park Jinseo , Frangaj Aurel , Sturchler Emmanuel , Zhou Ming , McDonald Patricia , Geng Yong , Slesinger Paul A. , Fan Qing R.
Published: April 2019

Metabotropic GABA
B
receptors mediate a significant fraction of inhibitory neurotransmission in the brain. Native GABA
B
receptor complexes contain the principal subunits GABA
B1
and GABA
B2
, which form an obligate heterodimer, and auxiliary subunits, known as potassium channel tetramerization domain-containing proteins (KCTDs). KCTDs interact with GABA
B
receptors and modify the kinetics of GABA
B
receptor signaling. Little is known about the molecular mechanism governing the direct association and functional coupling of GABA
B
receptors with these auxiliary proteins. Here, we describe the high-resolution structure of the KCTD16 oligomerization domain in complex with part of the GABA
B2
receptor. A single GABA
B2
C-terminal peptide is bound to the interior of an open pentamer formed by the oligomerization domain of five KCTD16 subunits. Mutation of specific amino acids identified in the structure of the GABA
B2
–KCTD16 interface disrupted both the biochemical association and functional modulation of GABA
B
receptors and G protein-activated inwardly rectifying K
+
channel (GIRK) channels. These interfacial residues are conserved among KCTDs, suggesting a common mode of KCTD interaction with GABA
B
receptors. Defining the binding interface of GABA
B
receptor and KCTD reveals a potential regulatory site for modulating GABA
B
-receptor function in the brain.
The Notch signaling pathway promotes basophil responses during helminth-induced type 2 inflammation
Authors: Webb Lauren M. , Oyesola Oyebola O. , Früh Simon P. , Kamynina Elena , Still Katherine M. , Patel Ravi K. , Peng Seth A. , Cubitt Rebecca L. , Grimson Andrew , Grenier Jennifer K. , Harris Tajie H. , Danko Charles G. , Tait Wojno Elia D.
Published: April 2019

Type 2 inflammation drives the clearance of gastrointestinal helminth parasites, which infect over two billion people worldwide. Basophils are innate immune cells that support host-protective type 2 inflammation during murine infection with the helminth Trichuris muris. However, the mechanisms required for basophil function and gene expression regulation in this context remain unclear. We show that during T. muris infection, basophils localized to the intestine and up-regulated Notch receptor expression, rendering them sensitive to Notch signals that rapidly regulate gene expression programs. In vitro, Notch inhibition limited basophil cytokine production in response to cytokine stimulation. Basophil-intrinsic Notch signaling was required for T. muris–elicited changes in genome-wide basophil transcriptional programs. Mice lacking basophil-intrinsic functional Notch signaling had impaired worm clearance, decreased intestinal type 2 inflammation, altered basophil localization in the intestine, and decreased CD4+ T helper 2 cell responses following infection. These findings demonstrate that Notch is required for basophil gene expression and effector function associated with helminth expulsion during type 2 inflammation.
Context-dependent EMT programs in cancer metastasis
Authors: Aiello Nicole M. , Kang Yibin
Published: April 2019

Epithelial–mesenchymal transition (EMT) is a developmental process whereby stationary, adherent cells acquire the ability to migrate. EMT is critical for dramatic cellular movements during embryogenesis; however, tumor cells can reactivate EMT programs, which increases their aggressiveness. In addition to motility, EMT is associated with enhanced stem cell properties and drug resistance; thus it can drive metastasis, tumor recurrence, and therapy resistance in the context of cancer. However, the precise requirements for EMT in metastasis have not been fully delineated, with different tumor types relying on discrete EMT effectors. Most tumor cells do not undergo a full EMT, but rather adopt some qualities of mesenchymal cells and maintain some epithelial characteristics. Emerging evidence suggests that partial EMT can drive distinct migratory properties and enhance the epithelial-mesenchymal plasticity of cancer cells as well as cell fate plasticity. This review discusses the diverse regulatory mechanisms and functional consequences of EMT, with an emphasis on the importance of partial EMT.
Elastic domains of giant proteins in striated muscle: Modeling compliance with rulers
Authors: Chase P. Bryant
Published: April 2019

Chase examines a study using the MUSICO model of striated muscle to evaluate the function of giant elastic proteins titin and nebulin.
Quasinormal modes of Dirac spinors in the background of rotating black holes in four and five dimensions
Authors: Blázquez-Salcedo Jose Luis , Knoll Christian
Published: April 2019

We study the quasinormal modes of massive Dirac spinors in the background of rotating black holes. In particular, we consider the Kerr geometry as well as the five dimensional Myers–Perry spacetime with equal angular momenta. We decouple the equations using the standard methods from the literature. In the five dimensional Myers–Perry black hole the angular equation is solved analytically. Using the continued fraction method, we calculate the spectrum of quasinormal modes for the ground modes and first excited modes. For the case of the Kerr black hole we also study some features of the modes with high overtone number. We analyze, in a systematic way, its dependence on the different parameters of the black hole and fermionic field. We compare our values with previous results available in the literature for Kerr and for the static limit. The numerical results show several differences between the four and five dimensional cases. For instance, in five dimensions the symmetry between the positive and negative (real) frequency of the modes breaks down, which results in a richer spectrum.
Residual flatness and scale calibration for a point autofocus surface topography measuring instrument
Authors: Maculotti Giacomo , Feng Xiaobing , Su Rong , Galetto Maurizio , Leach Richard
Published: April 2019

Point autofocus instruments are often used for measuring the surface topography of objects with complex geometry. Determining the metrological characteristics of the instrument is key to ensuring a traceable areal surface topography measurement. In this work, several metrological characteristics, as outlined in ISO/FDIS 25178-600, are determined for a commercial point autofocus instrument, including flatness deviation, the amplification and linearity of the lateral and vertical axes, and the perpendicularity between the axes. Calibrated material measures including an optical flat, step heights and areal cross gratings are used to determine the metrological characteristics. The impact of the point autofocus operating principle and the evaluation method on the metrological characteristics is discussed.
van der Waals-corrected density functional study of electric field noise heating in ion traps caused by electrode surface adsorbates
Authors: Ray Keith G , Rubenstein Brenda M , Gu Wenze , Lordi Vincenzo
Published: April 2019

In order to realize the full potential of ion trap quantum computers, an improved understanding is required of the motional heating that trapped ions experience. Experimental studies of the temperature-, frequency-, and ion–electrode distance-dependence of the electric field noise responsible for motional heating, as well as the noise before and after ion bombardment cleaning of trap electrodes, suggest that fluctuations of adsorbate dipoles are a likely source of so-called ‘anomalous heating,’ or motional heating of the trapped ions at a rate much higher than the Johnson noise limit. Previous computational studies have investigated how the fluctuation of model adsorbate dipoles affects anomalous heating. However, the way in which specific adsorbates affect the electric field noise has not yet been examined, and an electric dipole model employed in previous studies is only accurate for a small subset of possible adsorbates. Here, we analyze the behavior of both in-plane and out-of-plane vibrational modes of twenty-one adsorbate–electrode combinations within the independent fluctuating dipole model, utilizing accurate first principles computational methods to determine the surface-induced dipole moments. We find the chemical specificity of the adsorbate can change the electric field noise by seven orders of magnitude and specifically that soft in-plane modes of weakly-adsorbed hydrocarbons produce the greatest noise and ion heating. We discuss the dynamics captured by the fluctuating dipole model, namely the adsorbate-dependent turn-on temperature and electric field noise magnitude, and also discuss the model’s failure to reproduce the measured 1/ω noise frequency scaling with a single adsorbate species. We suggest future research directions for improved, quantitatively predictive models based on extensions of the present framework to multiple interacting adsorbates.
Cones of Heegner divisors
Authors: Bruinier Jan , Möller Martin
Published: April 2019

We show that the cone of primitive Heegner divisors is finitely generated for many orthogonal Shimura varieties, including the moduli space of polarized

K
3

K3

-surfaces. The proof relies on the growth of coefficients of modular forms.
Novel Contributors and Mechanisms of Cellular Senescence in Hypertension-Associated Premature Vascular Aging
Authors: McCarthy Cameron G , Wenceslau Camilla F , Webb R Clinton , Joe Bina
Published: April 2019

Hypertension has been described as a condition of premature vascular aging, relative to actual chronological age. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in hypertension. Nonetheless, the precise mechanisms that underlie the aged phenotype of arteries from hypertensive patients and animals remain elusive. Cellular senescence is an age-related physiologic process in which cells undergo irreversible growth arrest. Although controlled senescence negatively regulates cell proliferation and promotes tissue regeneration, uncontrolled senescence can contribute to disease pathogenesis by presenting the senescence-associated secretory phenotype, in which molecules such as proinflammatory cytokines, matrix metalloproteases, and reactive oxygen species are released into tissue microenvironments. This review will address and critically evaluate the current literature on the role of cellular senescence in hypertension, with particular emphasis on cells types that mediate and modulate vascular function and structure.
Role of Pendrin in the Pathophysiology of Aldosterone-Induced Hypertension
Authors: Shibata Shigeru
Published: April 2019

The recent advances in genetics and molecular biology have resulted in the characterization of key components that critically regulate renal NaCl transport and blood pressure. Pendrin is a Cl−/HCO3− exchanger that is highly expressed in thyroid, inner ear, and kidney. In the kidney, it is selectively present at the apical membrane in non-α intercalated cells of the connecting tubules and cortical collecting duct. Besides its role in acid/base homeostasis, accumulating studies using various genetically modified animals have provided compelling evidence that pendrin regulates extracellular fluid volume and electrolyte balance at the downstream of aldosterone signaling. We have shown that angiotensin II and aldosterone cooperatively control pendrin abundance partly through mammalian target of rapamycin signaling and mineralocorticoid receptor dephosphorylation, which is necessary for the kidney to prevent extracellular fluid loss and electrolyte disturbances under physiologic perturbations. In line with the experimental observations, several clinical data indicated that the impaired pendrin function can cause fluid and electrolyte abnormalities in humans. The purpose of this review is to provide an update on the recent progress regarding the role of pendrin in fluid and electrolyte homeostasis, as well as in the pathophysiology of hypertension associated with mineralocorticoid receptor signaling.
An overview of diffusion models for intracellular dynamics analysis
Authors: Briane Vincent , Vimond Myriam , Kervrann Charles
Published: April 2019

We present an overview of diffusion models commonly used for quantifying the dynamics of intracellular particles (e.g. biomolecules) inside eukaryotic living cells. It is established that inference on the modes of mobility of molecules is central in cell biology since it reflects interactions between structures and determines functions of biomolecules in the cell. In that context, Brownian motion is a key component in short distance transportation (e.g. connectivity for signal transduction). Another dynamical process that has been heavily studied in the past decade is the motor-mediated transport (e.g. dynein, kinesin and myosin) of molecules. Primarily supported by actin filament and microtubule network, it ensures spatial organization and temporal synchronization in the intracellular mechanisms and structures. Nevertheless, the complexity of internal structures and molecular processes in the living cell influence the molecular dynamics and prevent the systematic application of pure Brownian or directed motion modeling. On the one hand, cytoskeleton density will hinder the free displacement of the particle, a phenomenon called subdiffusion. On the other hand, the cytoskeleton elasticity combined with thermal bending can contribute a phenomenon called superdiffusion. This paper discusses the basics of diffusion modes observed in eukariotic cells, by introducing the essential properties of these processes. Applications of diffusion models include protein trafficking and transport and membrane diffusion.
PEPred-Suite: improved and robust prediction of therapeutic peptides using adaptive feature representation learning
Authors: Wei Leyi , Zhou Chen , Su Ran , Zou Quan
Published: April 2019

Motivation

Prediction of therapeutic peptides is critical for the discovery of novel and efficient peptide-based therapeutics. Computational methods, especially machine learning based methods, have been developed for addressing this need. However, most of existing methods are peptide-specific; currently, there is no generic predictor for multiple peptide types. Moreover, it is still challenging to extract informative feature representations from the perspective of primary sequences.

Results

In this study, we have developed PEPred-Suite, a bioinformatics tool for the generic prediction of therapeutic peptides. In PEPred-Suite, we introduce an adaptive feature representation strategy that can learn the most representative features for different peptide types. To be specific, we train diverse sequence-based feature descriptors, integrate the learnt class information into our features, and utilize a two-step feature optimization strategy based on the area under receiver operating characteristic curve to extract the most discriminative features. Using the learnt representative features, we trained eight random forest models for eight different types of functional peptides, respectively. Benchmarking results showed that as compared with existing predictors, PEPred-Suite achieves better and robust performance for different peptides. As far as we know, PEPred-Suite is currently the first tool that is capable of predicting so many peptide types simultaneously. In addition, our work demonstrates that the learnt features can reliably predict different peptides.

Availability and implementation

The user-friendly webserver implementing the proposed PEPred-Suite is freely accessible at http://server.malab.cn/PEPred-Suite.

Supplementary information

Supplementary data are available at Bioinformatics online.
Overlap graph-based generation of haplotigs for diploids and polyploids
Authors: Baaijens Jasmijn A , Schönhuth Alexander
Published: April 2019

Motivation

Haplotype-aware genome assembly plays an important role in genetics, medicine and various other disciplines, yet generation of haplotype-resolved de novo assemblies remains a major challenge. Beyond distinguishing between errors and true sequential variants, one needs to assign the true variants to the different genome copies. Recent work has pointed out that the enormous quantities of traditional NGS read data have been greatly underexploited in terms of haplotig computation so far, which reflects that methodology for reference independent haplotig computation has not yet reached maturity.

Results

We present POLYploid genome fitTEr (POLYTE) as a new approach to de novo generation of haplotigs for diploid and polyploid genomes of known ploidy. Our method follows an iterative scheme where in each iteration reads or contigs are joined, based on their interplay in terms of an underlying haplotype-aware overlap graph. Along the iterations, contigs grow while preserving their haplotype identity. Benchmarking experiments on both real and simulated data demonstrate that POLYTE establishes new standards in terms of error-free reconstruction of haplotype-specific sequence. As a consequence, POLYTE outperforms state-of-the-art approaches in various relevant aspects, where advantages become particularly distinct in polyploid settings.

Availability and implementation

POLYTE is freely available as part of the HaploConduct package at https://github.com/HaploConduct/HaploConduct, implemented in Python and C++.

Supplementary information

Supplementary data are available at Bioinformatics online.
Fast detection of maximal exact matches via fixed sampling of queryK-mers and Bloom filtering of indexK-mers
Authors: Liu Yuansheng , Zhang Leo Yu , Li Jinyan
Published: April 2019

Motivation

Detection of maximal exact matches (MEMs) between two long sequences is a fundamental problem in pairwise reference-query genome comparisons. To efficiently compare larger and larger genomes, reducing the number of indexed k-mers as well as the number of query k-mers has been adopted as a mainstream approach which saves the computational resources by avoiding a significant number of unnecessary matches.

Results

Under this framework, we proposed a new method to detect all MEMs from a pair of genomes. The method first performs a fixed sampling of k-mers on the query sequence, and adds these selected k-mers to a Bloom filter. Then all the k-mers of the reference sequence are tested by the Bloom filter. If a k-mer passes the test, it is inserted into a hash table for indexing. Compared with the existing methods, much less number of query k-mers are generated and much less k-mers are inserted into the index to avoid unnecessary matches, leading to an efficient matching process and memory usage savings. Experiments on large genomes demonstrate that our method is at least 1.8 times faster than the best of the existing algorithms. This performance is mainly attributed to the key novelty of our method that the fixed k-mer sampling must be conducted on the query sequence and the index k-mers are filtered from the reference sequence via a Bloom filter.

Availability and implementation

https://github.com/yuansliu/bfMEM

Supplementary information

Supplementary data are available at Bioinformatics online.
DeepSignal: detecting DNA methylation state from Nanopore sequencing reads using deep-learning
Authors: Ni Peng , Huang Neng , Zhang Zhi , Wang De-Peng , Liang Fan , Miao Yu , Xiao Chuan-Le , Luo Feng , Wang Jianxin
Published: April 2019

Motivation

The Oxford Nanopore sequencing enables to directly detect methylation states of bases in DNA from reads without extra laboratory techniques. Novel computational methods are required to improve the accuracy and robustness of DNA methylation state prediction using Nanopore reads.

Results

In this study, we develop DeepSignal, a deep learning method to detect DNA methylation states from Nanopore sequencing reads. Testing on Nanopore reads of Homo sapiens (H. sapiens), Escherichia coli (E. coli) and pUC19 shows that DeepSignal can achieve higher performance at both read level and genome level on detecting 6 mA and 5mC methylation states comparing to previous hidden Markov model (HMM) based methods. DeepSignal achieves similar performance cross different DNA methylation bases, different DNA methylation motifs and both singleton and mixed DNA CpG. Moreover, DeepSignal requires much lower coverage than those required by HMM and statistics based methods. DeepSignal can achieve 90% above accuracy for detecting 5mC and 6 mA using only 2× coverage of reads. Furthermore, for DNA CpG methylation state prediction, DeepSignal achieves 90% correlation with bisulfite sequencing using just 20× coverage of reads, which is much better than HMM based methods. Especially, DeepSignal can predict methylation states of 5% more DNA CpGs that previously cannot be predicted by bisulfite sequencing. DeepSignal can be a robust and accurate method for detecting methylation states of DNA bases.

Availability and implementation

DeepSignal is publicly available at https://github.com/bioinfomaticsCSU/deepsignal.

Supplementary information

Supplementary data are available at bioinformatics online.
Phylogeny of Thripophagini ovenbirds (Aves: Synallaxinae: Furnariidae)
Authors: Quintero Esther , Perktaş Utku
Published: April 2019

In this study, we address the evolutionary relationships and discuss the biogeographical history of a complex and diverse group of ovenbirds, the Thripophagini. We reconstruct the phylogeny and estimate the time of divergence of this group, using sequences from two complete mitochondrial genes (cytochrome b and NADH subunit 2) from a total of 115 fresh tissue samples. The results provide a better understanding of the phylogenetic relationships of the taxa within this group, some of which require a thorough taxonomic revision. We discuss the biogeographical history of the group, and find parallels with other previously studied Andean birds which may indicate that tectonic and climatic events might, at least in part, be linked to its diversification through the uplift of the Andes, the creation of new montane habitats and barriers, the evolution of Amazonian drainages and landscapes, and the climatic oscillations of the Pleistocene.
The National Council for Civil Liberties and the British State during the First World War, 1916–1919
Authors: Keil André
Published: April 2019

The First World War saw an unprecedented expansion of the executive powers of the British government that radically changed the relationship between individual citizens and the state. This article offers a new perspective on these developments by analysing the activities of the National Council for Civil Liberties (NCCL) between 1916 and 1918. It explores the emergence of civil liberties activism in Britain during the war and its impact on British political culture. The NCCL became an efficiently organised pressure group, campaigning against press censorship, political policing and the suppression of anti-war dissent. This article argues that the innovative campaigning and propaganda methods used by the NCCL mark a moment of innovation that can be described as a revolution in activism. It represents a shift from the grass-roots political associations of the nineteenth century towards more professional forms of political activism that foreshadowed the rise of modern pressure groups and NGOs. The article also explains the emergence of a new discourse about the relationship between civil liberties, democracy and socialism in Britain during the First World War. The NCCL became an important locus for the networks of protest and dissent that emerged in Britain in response to the expansion of the wartime state. The article thus presents a new perspective on the beginnings of civil liberties activism in Britain and the impact of the First World War on its political culture.
Associations Between Self-Reported Sensory Impairment and Risk of Cognitive Decline and Impairment in the Health and Retirement Study Cohort
Authors: Maharani Asri , Dawes Piers , Nazroo James , Tampubolon Gindo , Pendleton Neil ,   Sense-Cog WP1 Group, Bertelsen Geir , Cosh Suzanne , Cougnard-Grégoire Audrey , Dawes Piers , Delcourt Cécile , Constantinidou Fofi , Goedegebure Andre , Helmer Catherine , Ikram M Arfan , Klaver Caroline C W , Leroi Iracema , Maharani Asri , Meester-Smor Magda , Nael Virginie , Oosterloo Neelke , Pendleton Neil , Schirmer Henrik , Tampubolon Gindo , Tiemeier Henning , von Hanno Therese
Published: April 2019

Objectives

We aimed to determine whether self-assessed single (hearing or visual) and dual sensory (hearing and visual) impairments are associated with cognitive decline and incident possible cognitive impairment, no dementia (CIND) and probable dementia.

Method

Data were drawn from the 1996–2014 surveys of the Health and Retirement Study (HRS), involving 19,618 respondents who had no probable dementia and who were aged 50 years or older at the baseline. We used linear mixed models to test the association between self-assessed sensory impairment and cognitive decline followed by a Cox proportional hazard model to estimate the relative risk of incident possible CIND and probable dementia associated with the presence of sensory impairment.

Results

Respondents with self-assessed single and dual sensory impairment performed worse in cognitive tests than those without sensory impairment. The fully adjusted incidence of developing possible CIND was 17% higher for respondents with hearing impairment than those without hearing impairment. Respondents with visual impairment had 35% and 25% higher risk for developing possible CIND and probable dementia, respectively, than those without visual impairment. Respondents with dual sensory impairment at baseline were 38% and 26% more likely to develop possible CIND and probable dementia, respectively, than those with no sensory impairment.

Discussion

Self-assessed sensory impairment is independently associated with cognitive decline and incident possible CIND and probable dementia. Further studies are needed to identify the mechanism underlying this association and to determine whether treatment of sensory impairment could ameliorate cognitive decline and delay the onset of dementia among older adults.
Dysregulation of NRAP degradation by KLHL41 contributes to pathophysiology in nemaline myopathy
Authors: Jirka Caroline , Pak Jasmine H , Grosgogeat Claire A , Marchetii Michael Mario , Gupta Vandana A
Published: April 2019

Nemaline myopathy (NM) is the most common form of congenital myopathy that results in hypotonia and muscle weakness. This disease is clinically and genetically heterogeneous, but three recently discovered genes in NM encode for members of the Kelch family of proteins. Kelch proteins act as substrate-specific adaptors for Cullin 3 (CUL3) E3 ubiquitin ligase to regulate protein turnover through the ubiquitin-proteasome machinery. Defects in thin filament formation and/or stability are key molecular processes that underlie the disease pathology in NM; however, the role of Kelch proteins in these processes in normal and diseases conditions remains elusive. Here, we describe a role of NM causing Kelch protein, KLHL41, in premyofibil-myofibil transition during skeletal muscle development through a regulation of the thin filament chaperone, nebulin-related anchoring protein (NRAP). KLHL41 binds to the thin filament chaperone NRAP and promotes ubiquitination and subsequent degradation of NRAP, a process that is critical for the formation of mature myofibrils. KLHL41 deficiency results in abnormal accumulation of NRAP in muscle cells. NRAP overexpression in transgenic zebrafish resulted in a severe myopathic phenotype and absence of mature myofibrils demonstrating a role in disease pathology. Reducing Nrap levels in KLHL41 deficient zebrafish rescues the structural and function defects associated with disease pathology. We conclude that defects in KLHL41-mediated ubiquitination of sarcomeric proteins contribute to structural and functional deficits in skeletal muscle. These findings further our understanding of how the sarcomere assembly is regulated by disease-causing factors in vivo, which will be imperative for developing mechanism-based specific therapeutic interventions.
Late-stage obstruction due to preventative wrapping of left ventricular assist device outflow graft
Authors: Hsu Steven , Freed Kristin E , Choi Chun W , Kilic Ahmet
Published: April 2019

Preventative polytetrafluoroethylene coverings are often used to protect the left ventricular assist device outflow graft during sternal re-entry. We herein describe 5 cases of late-onset, significant left ventricular assist device outflow graft obstruction due to external outflow graft compression. We present clinical presentations, therapies and outcomes.
Adding tricuspid repair to standard open heart surgery does not increase risk but improves right ventricular function
Authors: Pingpoh Clarence , Nuss Sarah , Kueri Sami , Kreibich Maximillian , Czerny Martin , Beyersdorf Friedhelm , Siepe Matthias
Published: April 2019

OBJECTIVES

To evaluate outcome of concomitant tricuspid annuloplasty in mild or moderate regurgitation on perioperative outcome and on right ventricular function in patients undergoing major cardiac surgery.

METHODS

Among 14 500 patients who underwent cardiac surgery at our institution between January 2000 and April 2016, 1023 patients had a documented history of tricuspid regurgitation (TR). Of those patients, 324 patients were diagnosed with mild or moderate secondary TR with a dilated annulus (≥40 mm or >21 mm/m2) and composed the study population. The decision to perform concomitant annuloplasty was subjected to the individual decision of the treating surgeon. Our analysis focused on a comparison between patients with concomitant TR-repair (group 1, n = 184) and patients without concomitant TR-repair (group 2, n = 140) after propensity score matching.

RESULTS

Following a preliminary data preprocessing, we observed a mean age of 73.8 years, mean logistic EuroSCORE of 10.5%. Perioperative mortality was 4.4% in group 1 and 5.7% in group 2. There was no significant difference in mid-term mortality. TR after surgery was significantly higher in group 2. After propensity score matching regression analysis, patients who had a repaired tricuspid valve (group 1) had better right ventricle (RV) function than those without TR-repair (group 2) (P > 0.05 at 95% confidence interval following Kolmogorov–Smirnov Goodness of fit Test).

CONCLUSIONS

Adding tricuspid valve repair in patients with mild or moderate secondary TR with a dilated annulus (≥40 mm or >21 mm/m2) to standard open heart surgery does not increase perioperative risk but improves right ventricular function. Therefore, standard tricuspid repair in this subgroup might be considered on a routine basis.
Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and risk of total and cause-specific mortality: results from the Golestan Cohort Study
Authors: Mokhtari Zeinab , Sharafkhah Maryam , Poustchi Hossein , Sepanlou Sadaf G , Khoshnia Masoud , Gharavi Abdolsamad , Sohrabpour Amir Ali , Sotoudeh Masoud , Dawsey Sanford M , Boffetta Paolo , Abnet Christian C , Kamangar Farin , Etemadi Arash , Pourshams Akram , FazeltabarMalekshah Akbar , Islami Farhad , Brennan Paul , Malekzadeh Reza , Hekmatdoost Azita
Published: April 2019

Objective

To evaluate the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and overall and cause-specific mortality in the Golestan Cohort Study (GCS).

Methods

A total of 50 045 participants aged 40 years or older were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a mean of 10.64 years. The DASH diet score was calculated for each individual based on food groups. The primary outcome measure was death from any cause.

Results

During 517 326 person-years of follow-up, 6763 deaths were reported. After adjustment for potential confounders, DASH diet score was inversely associated with risk of death from all causes and cancers [hazard ratio (HR): 0.86; 95% confidence interval (CI): 0.75, 0.98; and HR: 0.65; 95% CI: 0.47, 0.90, respectively]. A higher DASH diet score was associated with lower risk of gastrointestinal cancer mortality in men (HR: 0.55; 95% CI: 0.30, 0.99). A greater adherence to DASH diet was also associated with lower other-cancer mortality in women (HR: 0.50; 95% CI: 0.24, 0.99). No association between DASH diet score and cardiovascular disease mortality was observed, except that those dying of cardiovascular disease were younger than 50 years of age and smokers.

Conclusions

Our findings suggest that maintaining a diet similar to the DASH diet is independently associated with reducing the risk of total death, cancers, and especially gastrointestinal cancers in men.
Software application profile: the Rapid Inquiry Facility 4.0: an open access tool for environmental public health tracking
Authors: Piel Frédéric B , Parkes Brandon , Hambly Peter , Roca-Barceló Aina , McCallion Martin , Leonardi Giovanni , Strosnider Heather , Yip Fuyuen , Elliott Paul , Hansell Anna L
Published: April 2019

The Rapid Inquiry Facility 4.0 (RIF) is a new user-friendly and open-access tool, developed by the UK Small Area Health Statistics Unit (SAHSU), to facilitate environment public health tracking (EPHT) or surveillance (EPHS). The RIF is designed to help public health professionals and academics to rapidly perform exploratory investigations of health and environmental data at the small-area level (e.g. postcode or detailed census areas) in order to identify unusual signals, such as disease clusters and potential environmental hazards, whether localized (e.g. industrial site) or widespread (e.g. air and noise pollution). The RIF allows the use of advanced disease mapping methods, including Bayesian small-area smoothing and complex risk analysis functionalities, while accounting for confounders. The RIF could be particularly useful to monitor spatio-temporal trends in mortality and morbidity associated with cardiovascular diseases, cancers, diabetes and chronic lung diseases, or to conduct local or national studies on air pollution, flooding, low-magnetic fields or nuclear power plants.
Keeping the Engine Running: The Relevance and Predictive Value of Preclinical Models for CAR-T Cell Development
Authors: Migliorini Denis , Mason Nicola J , Posey Avery D
Published: April 2019

The cellular immunotherapy field has achieved important milestones in the last 30 years towards the treatment of a variety of cancers due to improvements in ex-vivo T cell manufacturing processes, the invention of synthetic T cell receptors, and advances in cellular engineering. Here, we discuss major preclinical models that have been useful for the validation of chimeric antigen receptor (CAR)-T cell therapies and also promising new models that will fuel future investigations towards success. However, multiple unanswered questions in the CAR-T cell field remain to be addressed that will require innovative preclinical models. Key challenges facing the field include premature immune rejection of universal CAR-T cells and the immune suppressive tumor microenvironment. Immune competent models that accurately recapitulate tumor heterogeneity, the hostile tumor microenvironment, and barriers to CAR-T cell homing, toxicity, and persistence are needed for further advancement of the field.
A New Affine Invariant Geometric Functional for Polytopes and Its Associated Affine Isoperimetric Inequalities
Authors: Hu Jiaqi , Xiong Ge
Published: April 2019

A new affine invariant geometric functional for convex polytopes is introduced. Some new sharp affine isoperimetric inequalities are established for this new functional, which are extensions of Lutwak–Yang–Zhang’s results on their celebrated cone-volume functional.
Discrimination in the Age of Algorithms
Authors: Kleinberg Jon , Ludwig Jens , Mullainathan Sendhil , Sunstein Cass R
Published: April 2019

The law forbids discrimination. But the ambiguity of human decision-making often makes it hard for the legal system to know whether anyone has discriminated. To understand how algorithms affect discrimination, we must understand how they affect the detection of discrimination. With the appropriate requirements in place, algorithms create the potential for new forms of transparency and hence opportunities to detect discrimination that are otherwise unavailable. The specificity of algorithms also makes transparent tradeoffs among competing values. This implies algorithms are not only a threat to be regulated; with the right safeguards, they can be a potential positive force for equity.
Loss of mismatch repair signaling impairs the WNT–bone morphogenetic protein crosstalk and the colonic homeostasis
Authors: Nørgaard Katrine , Müller Carolin , Christensen Nadja , Chiloeches María L , Madsen Cesilie L , Nielsen Sabine S , Thingholm Tine E , Belcheva Antoaneta
Published: April 2019

The fine balance between proliferation, differentiation, and apoptosis in the colonic epithelium is tightly controlled by the interplay between WNT, Notch, and bone morphogenetic protein (BMP) signaling. How these complex networks coordinate the colonic homeostasis, especially if cancer predisposing mutations such as mutations in the DNA mismatch repair (MMR) are present, is unclear. Inactivation of the MMR system has long been linked to colorectal cancer; however, little is known about its role in the regulation of the colonic homeostasis. It has been shown that loss of MMR promotes the proliferation of colon epithelial cells that renders them highly susceptible to transformation. The mechanism through which MMR mediates this effect, yet, remains to be determined. Using an MMR-deficient mouse model, we show that increased methylation of Dickkopf1 impacts its expression, and consequently, the ability to negatively regulate WNT signaling. As a result, excessive levels of active β-catenin promote strong crypt progenitor-like phenotype and abnormal proliferation. Under these settings, the development and function of the goblet cells are affected. MMR-deficient mice have fewer goblet cells with enlarged mucin-loaded vesicles. We further show that MMR inactivation impacts the WNT–BMP signaling crosstalk.
Parental Involvement and Executive Function in Emerging Adults with Type 1 Diabetes
Authors: Berg Cynthia A , Wiebe Deborah J , Lee Tracy Eunjin , Kelly Caitlin S , Mello Daniel , Turner Sara L , Butner Jonathan E , Munion Ascher K , Mansfield Jessica H , White Perrin C , Murray Mary , Suchy Yana
Published: April 2019

Objective

To examine (a) changes in parental involvement across early emerging adulthood, (b) whether yearly fluctuations in parental involvement were associated with adherence and glycated hemoglobin (HbA1c) over time, and (c) whether higher involvement was more beneficial for those with poorer executive function (EF).

Methods

A total of 228 high school seniors (M age = 17.76) with type 1 diabetes reported on mothers’ and fathers’ acceptance, knowledge of diabetes activities, disclosure to mothers and fathers regarding diabetes, and adherence at four yearly time points. At baseline, participants completed performance-based measures of EF. HbA1c was collected from assay kits.

Results

Growth curve models revealed significant declines in disclosure to fathers and mothers’ and fathers’ knowledge of diabetes activities; no changes were found in mothers’ or fathers’ acceptance nor disclosure to mothers. Multilevel models indicated significant between-person effects for nearly all aspects of parental involvement with more acceptance, knowledge, and disclosure associated with better HbA1c and adherence. Within-person effects for disclosure to fathers, and mothers’ and fathers’ knowledge indicated that in years when emerging adults perceived higher amounts of these types of involvement (compared with their own average), HbA1c was lower. Within-person effects were found for acceptance to mothers, disclosure to mothers and fathers, and mothers’ diabetes knowledge for adherence. Disclosure to fathers and mothers’ knowledge of diabetes activities were especially beneficial for HbA1c for those with poorer EF performance.

Conclusions

Parental involvement in diabetes management remains important during the high-risk time of emerging adulthood, especially for those with poorer EF.
The importance of slow canopy wilting in drought tolerance in soybean
Authors: Ye Heng , Song Li , Schapaugh William T , Ali Md Liakat , Sinclair Thomas R , Riar Mandeep K , Mutava Raymond N , Li Yang , Vuong Tri , Valliyodan Babu , Pizolato Neto Antonio , Klepadlo Mariola , Song Qijian , Shannon J Grover , Chen Pengyin , Nguyen Henry T
Published: April 2019

Physiological mechanisms of slow canopy wilting in early maturity group soybeans were identified and the underlying QTLs were mapped and confirmed to protect soybean yield under drought in the field.
Gravity sensing and signal conversion in plant gravitropism
Authors: Nakamura Moritaka , Nishimura Takeshi , Morita Miyo Terao
Published: April 2019

Plant organs control their growth orientation in response to gravity. Within gravity-sensing cells, the input (gravity sensing) and signal conversion (gravity signalling) progress sequentially. The cells contain a number of high-density, starch-accumulating amyloplasts, which sense gravity when they reposition themselves by sedimentation to the bottom of the cell when the plant organ is re-orientated. This triggers the next step of gravity signalling, when the physical signal generated by the sedimentation of the amyloplasts is converted into a biochemical signal, which redirects auxin transport towards the lower flank of the plant organ. This review focuses on recent advances in our knowledge of the regulatory mechanisms that underlie amyloplast sedimentation and the system by which this is perceived, and on recent progress in characterising the factors that play significant roles in gravity signalling by which the sedimentation is linked to the regulation of directional auxin transport. Finally, we discuss the contribution of gravity signalling factors to the mechanisms that control the gravitropic set-point angle.
Plastoglobular protein 18 is involved in chloroplast function and thylakoid formation
Authors: Espinoza-Corral Roberto , Heinz Steffen , Klingl Andreas , Jahns Peter , Lehmann Martin , Meurer Jörg , Nickelsen Jörg , Soll Jürgen , Schwenkert Serena
Published: April 2019

Plastoglobules are lipoprotein particles that are found in different types of plastids. They contain a very specific and specialized set of lipids and proteins. Plastoglobules are highly dynamic in size and shape, and are therefore thought to participate in adaptation processes during either abiotic or biotic stresses or transitions between developmental stages. They are suggested to function in thylakoid biogenesis, isoprenoid metabolism, and chlorophyll degradation. While several plastoglobular proteins contain identifiable domains, others provide no structural clues to their function. In this study, we investigate the role of plastoglobular protein 18 (PG18), which is conserved from cyanobacteria to higher plants. Analysis of a PG18 loss-of-function mutant in Arabidopsis thaliana demonstrated that PG18 plays an important role in thylakoid formation; the loss of PG18 results in impaired accumulation, assembly, and function of thylakoid membrane complexes. Interestingly, the mutant accumulated less chlorophyll and carotenoids, whereas xanthophyll cycle pigments were increased. Accumulation of photosynthetic complexes is similarly affected in both a Synechocystis and an Arabidopsis PG18 mutant. However, the ultrastructure of cyanobacterial thylakoids is not compromised by the lack of PG18, probably due to its less complex architecture.
Learning from Conditionals
Authors: Eva Benjamin , Hartmann Stephan , Rad Soroush Rafiee
Published: April 2019

In this article, we address a major outstanding question of probabilistic Bayesian epistemology: how should a rational Bayesian agent update their beliefs upon learning an indicative conditional? A number of authors have recently contended that this question is fundamentally underdetermined by Bayesian norms, and hence that there is no single update procedure that rational agents are obliged to follow upon learning an indicative conditional. Here we resist this trend and argue that a core set of widely accepted Bayesian norms is sufficient to identify a normatively privileged updating procedure for this kind of learning. Along the way, we justify a privileged formalization of the notion of ‘epistemic conservativity’, offer a new analysis of the Judy Benjamin problem, and emphasize the distinction between interpreting the content of new evidence and updating one’s beliefs on the basis of that content.
Inference of Ancient Whole-Genome Duplications and the Evolution of Gene Duplication and Loss Rates
Authors: Zwaenepoel Arthur , Van de Peer Yves
Published: April 2019

Gene tree–species tree reconciliation methods have been employed for studying ancient whole-genome duplication (WGD) events across the eukaryotic tree of life. Most approaches have relied on using maximum likelihood trees and the maximum parsimony reconciliation thereof to count duplication events on specific branches of interest in a reference species tree. Such approaches do not account for uncertainty in the gene tree and reconciliation, or do so only heuristically. The effects of these simplifications on the inference of ancient WGDs are unclear. In particular, the effects of variation in gene duplication and loss rates across the species tree have not been considered. Here, we developed a full probabilistic approach for phylogenomic reconciliation-based WGD inference, accounting for both gene tree and reconciliation uncertainty using a method based on the principle of amalgamated likelihood estimation. The model and methods are implemented in a maximum likelihood and Bayesian setting and account for variation of duplication and loss rates across the species tree, using methods inspired by phylogenetic divergence time estimation. We applied our newly developed framework to ancient WGDs in land plants and investigated the effects of duplication and loss rate variation on reconciliation and gene count based assessment of these earlier proposed WGDs.