bluuebunny/crossref_metadata_2025 huggingface dataset:
The genetic architecture of fruit colour in strawberry (Fragaria × ananassa) uncovers the predominant contribution of theF. vescasubgenome to anthocyanins and reveals underlying genetic variations
Authors: Labadie Marc , Vallin Guillaume , Petit Aurélie , Ring Ludwig , Hoffmann Thomas , Gaston Amèlia , Potier Aline , Munoz-Blanco Juan , Caballero José L. , Schwab Wilfried , Rothan Christophe , Denoyes Béatrice
Published: June 2020

Fruit colour, which is central to the sensorial and nutritional quality of the fruit, is a major breeding target in cultivated strawberry (Fragaria × ananassa). Red fruit colour is caused by the accumulation of anthocyanins, which are water-soluble flavonoids. Here, using pseudo F1progeny derived from the cv. ‘Capitola’ and the advanced line ‘CF1116’ and taking advantage of the available high density SNP array, we delineated fruit flavonoids mQTLs (13 compounds: anthocyanin, flavonols and flavan-3-ols) and colour-related QTLs (total anthocyanins and fruit colour) to narrow genomic regions corresponding to specific subgenomes of the cultivated strawberry. Findings showed that the overwhelming majority of the anthocyanin mQTLs and other colour-related QTLs are specific toF. vescasubgenome but that other subgenomes also contribute to colour variations. We then focused on two major homoeo-mQTLs for pelargonidin-3-glucoside (PgGs) localized on both male and female maps on linkage group LG3a (F. vescasubgenome). Combined high-resolution mapping of PgGs mQTLs and colour QTLs, transcriptome analysis of selected progeny individuals and whole genome sequencing of the parents led to the identification of several INDELS in thecis-regulatory region of aMYB102-like ODORANTgene and of the deletion of a putative MADS box binding motif in the 5’UTR upstream region of an anthocyanidin reductase (ANR)gene, which likely underlie significant colour variations in strawberry fruit. The implications of these findings are important for the functional analysis and genetic engineering of colour-related genes and for the breeding by Marker-Assisted-Selection of new strawberry varieties with improved colour and health-benefits.
Cycling and prostate cancer risk – Bayesian insights from observational study data
Authors: Vincent Benjamin T.
Published: June 2020

Men have a very high lifetime risk of developing prostate cancer, and so there is a pressing need to understand factors that influence this risk. One factor of interest is whether cycling increases of decreases prostate cancer lifetime risk. Two large observational studies of cyclists noted very low rates of prostate cancer amongst cyclists relative to the general population – neither however drew causal conclusions about risk based on this observational prevalence data alone. Here we explore if and how we can use such data to update our beliefs about whether cycling increases or decreases prostate cancer risk – we use probabilistic methods to quantify belief in risk given the observational data available. We examine whether there is a dose– response relationship, how we can make inferences about risks, and the impact upon selection bias upon these inferences. A simple analysis leads us to believe that cycling decreases risk, but we show how this is mistaken unless selection bias can be ruled out. If cyclists who develop prostate cancer are less likely to respond to these surveys, we may be mislead into believing that cycling decreases risk even if it actually increases risk. Overall we explore precisely why it is hard to draw conclusions about risk factors based upon observational prevalence data.
Top-down contextual requirement to suppress self-movement influences grasp-specific modulation of corticospinal excitability during action observation
Authors: Jerjian Steven J. , Davare Marco , Kraskov Alexander
Published: June 2020

Action observation modulates corticospinal excitability (CSE) measured via transcranial magnetic stimulation (TMS) in humans, which presumably exposes the effect of mirror neuron activation on corticospinal pathways. These responses can consist of both facilitation and suppression, and the balance of these two may restrict the outflow of activity into movement. Evidence also suggests that task context can considerably influence CSE changes during action observation.

Here, we assessed whether embedding action observation within a Go-NoGo paradigm, emphasizing movement withholding on observation and NoGo trials, influenced CSE modulation. Fourteen healthy subjects received single pulse TMS over left primary motor cortex (M1) during a baseline period, grasp observation onset, or after a NoGo cue, while performing, observing, or withholding two distinct reach-to-grasp actions. We assessed modulation of motor evoked potentials (MEPs) in three intrinsic hand muscles, which were recruited in a grasp-specific manner during action execution. CSE modulation was limited, and predominantly suppressive in nature during grasp observation. Seven subjects performed the same task without the NoGo condition (“Go-only” block) immediately before the “Go&NoGo” block. We found evidence for grasp-specific modulation of CSE, which matched the recruitment pattern of the muscles during action execution. Within these subjects, modulation was attenuated when the NoGo condition was introduced, but was still distinct from modulation in the first group.

These results suggest that bottom-up grasp-specific modulation of MEPs during action observation is attenuated by the top-down contextual requirement to suppress self-movement, and facilitation and suppression effects are determined by the balance between these two processes.

SIGNIFICANCE STATEMENT

Action observation can activate specific pathways in the motor system of the observer, which are also used to perform the same action. This motor resonance, measured via changes in corticospinal excitability using transcranial magnetic stimulation, is susceptible to task context. In this study, we show that observing grasping actions results in grasp-specific changes in excitability, consistent with mirror neuron activation, but this effect is masked when observation is interleaved within a Go-NoGo paradigm, which emphasises suppression of one’s own movement. Top-down task requirements to withhold movement within and across trials, which are present in most action observation studies, likely influence the extent of motor resonance, urging caution in the design and interpretation of results in TMS action observation experiments.
Functional Redundancy in Local Spatial Scale Microbial Communities Suggest Stochastic Processes at an Urban Wilderness Preserve in Austin, TX, USA
Authors: Stewart Justin , Ontai Amy , Yusoof Kizil , Bilinski Teresa
Published: June 2020

Empirical evidence supports selection of soil microbial communities by edaphic properties across large spatial scales, however; less is known as smaller spatial scales (e.g 10s-100s of meters). The goal of this research was to evaluate the relationship between ecosystem characteristics and bacterial community structure/function in soils across small spatial scales in an urban preserve. We employed 16s rRNA gene sequencing, community level physiological profiling (CLPP), and soil chemical analysis to address this goal. We found no significant relationship between gradients in soil characteristics and community structure/function. In contrast,Acidobacteria, Bacteroidetes, andNitrospiraeresponded to variation in edaphic properties. Taxa exhibited a wide range in dispersal, supporting our finding of community wide differences in taxonomy. Furthermore, there was high metabolic diversity within the bacterial communities despite preferential metabolism of water-soluble polymers (Tween 40/80). Carbon substrate utilization patterns also suggest dominance of functional generalists. Pairwise comparison of carbon substrate utilization patterns indicates that there are high levels of microbial functional redundancy within soils across the sampling area. Lastly, we found that edaphic properties did not shape the overall community structure and/or function, and our analyses suggest that stochasticity may play a role in bacterial community assembly in soils with the local spatial scale of this research study.

Graphical Abstract

One Sentence Summary: Microorganisms at small spatial scales were functionally similar despite subtle differences in community composition.
Network-aware reaction pattern recognition reveals regulatory signatures of mitochondrial dysfunction
Authors: Berg Jordan A. , Zhou Youjia , Ouyang Yeyun , Waller T. Cameron , Cluntun Ahmad A. , Conway Megan E. , Nowinski Sara M. , Van Ry Tyler , George Ian , Cox James E. , Wang Bei , Rutter Jared
Published: June 2020

Metabolism forms a complex, interdependent network, and perturbations can have indirect effects that are pervasive. Identifying these patterns and their consequences is difficult, particularly when the effects occur across canonical pathways, and these difficulties have long acted as a bottleneck in metabolic data analysis. This challenge is compounded by technical limitations in metabolomics approaches that garner incomplete datasets. Current network-based tools generally utilize pathway-level analysis lacking the granular resolution required to provide context into the effects of all perturbations, regardless of magnitude, across the metabolic network. To address these shortcomings, we introduce algorithms that allow for the real-time extraction of regulatory patterns and trends from user data. To minimize the impact of missing measurements within the metabolic network, we introduce methods that enable complex pattern recognition across multiple reactions. These tools are available interactively within the user-friendly Metaboverse app (https://github.com/Metaboverse) to facilitate exploration and hypothesis generation. We demonstrate that expected signatures are accurately captured by Metaboverse. Using public lung adenocarcinoma data, we identify a previously undescribed multi-dimensional signature that correlated with survival outcomes in lung adenocarcinoma patients. Using a model of respiratory deficiency, we identify relevant and previously unreported regulatory patterns that suggest an important compensatory role for citrate during mitochondrial dysfunction. This body of work thus demonstrates that Metaboverse can identify and decipher complex signals from data that have been otherwise difficult to identify with previous approaches.
A meta-analysis of the inhibin network reveals prognostic value in multiple solid tumors
Authors: Listik Eduardo , Horst Ben , Choi Alex Seok , Lee Nam. Y. , Győrffy Balázs , Mythreye Karthikeyan
Published: June 2020

Inhibins and activins are dimeric ligands belonging to the TGFβ superfamily with emergent roles in cancer. Inhibins contain an α-subunit (INHA) and a β-subunit (eitherINHBAorINHBB), while activins are mainly homodimers of either βA(INHBA) or βB(INHBB) subunits. Inhibins are biomarkers in a subset of cancers and utilize the coreceptors betaglycan (TGFBR3) and endoglin (ENG) for physiological or pathological outcomes. Given the array of prior reports on inhibin, activin and the coreceptors in cancer, this study aims to provide a comprehensive analysis, assessing their functional prognostic potential in cancer using a bioinformatics approach. We identify cancer cell lines and cancer types most dependent and impacted, which included p53 mutated breast and ovarian cancers and lung adenocarcinomas. Moreover,INHAitself was dependent onTGFBR3andENGin multiple cancer types.INHA,INHBA,TGFBR3,andENGalso predicted patients’ response to anthracycline and taxane therapy in luminal A breast cancers. We also obtained a gene signature model that could accurately classify 96.7% of the cases based on outcomes. Lastly, we cross-compared gene correlations revealingINHAdependency toTGFBR3orENGinfluencing different pathways themselves. These results suggest that inhibins are particularly important in a subset of cancers depending on the coreceptorTGFBR3andENGand are of substantial prognostic value, thereby warranting further investigation.
Expression of HPV oncogenes from a single integration site in cervical cancer cell lines
Authors: Yu Lulu , Lobanov Alexei , Majerciak Vladimir , Mirza Sameer , Band Vimla , Liu Haibin , Cam Maggie , Zheng Zhi-Ming
Published: June 2020

Integration of a virus genome into human chromosomal DNA is critical in viral carcinogenesis. In this report, we discovered that virus-host fusion transcripts are characteristically originated mainly from a single integration site in three cervical cancer cell lines, CaSki and SiHa cells with multiple HPV16 DNA integration sites and HeLa cells with multiple HPV18 DNA integration sites. The host genomic elements surrounding the integrated HPV genome are critical for efficient expression of the viral oncogenes. We found that HPV E6 and E7 are expressed by hijacking a host 3’ splice site and/or RNA polyadenylation signal for their production. The viral-host fusion transcripts may encode a chimeric viral-host fusion protein through alternative RNA splicing. One such E6* protein in SiHa cells was found to antagonize E6 function and knockdown of its expression further decreased p53 protein level and increased cell growth by promoting S phase entry. Together, our findings of the integrated virus genome expression only from a given integrated host genomic site will shed new light on possible application of precision medicine and the understanding of HPV carcinogenesis.
Establishing the Effect of Vascular Structure on Laser Speckle Contrast Imagining
Authors: Jafari Chakameh Z. , Sullender Colin T. , Miller David R. , Mihelic Samuel A. , Dunn Andrew K.
Published: June 2020

Laser Speckle Contrast Imaging (LSCI) is a powerful tool for non-invasive, real-time imaging of blood flow in tissue. However, the effect of tissue geometry on the form of the electric field autocorrelation function and speckle contrast values is yet to be investigated. In this paper, we present an ultrafast forward model for simulating a speckle contrast image with the ability to rapidly update the image for a desired illumination pattern and flow perturbation. We demonstrate the first simulated speckle contrast image and compare it against experimental results. We simulate three mouse-specific cerebral cortex decorrelation time images and implement three different schemes for analyzing the effects of homogenization of vascular structure on correlation decay times. Our results indicate that dissolving structure and assuming homogeneous geometry creates up to ∼ 10x shift in the correlation function decay times and alters its form compared with the case for which the exact geometry is simulated. These effects are more pronounced for point illumination and detection imaging schemes. Further analysis indicates that correlated multiple scattering events, on average, account for 50% of all dynamic scattering events for a detector over a vessel region and 31% that of a detector over parenchyma region, highlighting the significance of accurate modeling of the three-dimensional vascular geometry for accurate blood flow estimates.
Aneuploid cells activate NF-κB to promote their immune clearance by NK cells
Authors: Wang Ruoxi W. , Viganò Sonia , Ben-David Uri , Amon Angelika , Santaguida Stefano
Published: June 2020

The immune system plays a major role in the protection against cancer. Identifying and characterizing the pathways mediating this immune surveillance is thus critical for understanding how cancer cells are recognized and eliminated. We previously found that untransformed cells that had undergone senescence due to highly abnormal karyotypes are eliminated by Natural Killer (NK) cellsin vitro. Here we show that this is also true for aneuploid untransformed cells that had not lost their ability to proliferate. Their elimination by NK cells, like that of aneuploid senescent cells, is predominantly mediated by non-cell autonomous mechanisms. Our data further indicate that NF-κB signaling in aneuploid cells is central to eliciting this immune response. Inactivating NF-κB abolishes NK-cell mediated clearance in aneuploid cellsin vitro. In cancer cell lines, NF-κB signaling correlates with degree of aneuploidy, raising the possibility that aneuploidy-induced immune recognition is partially retained in cancer.
Scalable learning of interpretable rules for the dynamic microbiome domain
Authors: Maringanti Venkata Suhas , Bucci Vanni , Gerber Georg K.
Published: June 2020

The microbiome, which is inherently dynamic, plays essential roles in human physiology and its disruption has been implicated in numerous human diseases. Linking dynamic changes in the microbiome to the status of the human host is an important problem, which is complicated by limitations and complexities of the data. Model interpretability is key in the microbiome field, as practitioners seek to derive testable biological hypotheses from data or develop diagnostic tests that can be understood by clinicians. Interpretable structure must take into account domainspecific information key to biologists and clinicians including evolutionary relationships (phylogeny) and dynamic behavior of the microbiome. A Bayesian model was previously developed in the field, which uses Markov Chain Monte Carlo inference to learn human interpretable rules for classifying the status of the human host based on microbiome time-series data, but that approach is not scalable to increasingly large microbiome datasets being produced. We present a new fully-differentiable model that also learns human-interpretable rules for the same classification task, but in an end-to-end gradient-descent based framework. We validate the performance of our model on human microbiome data sets and demonstrate our approach has similar predictive performance to the fully Bayesian method, while running orders-of-magnitude faster and moreover learning a larger set of rules, thus providing additional biological insight into the effects of diet and environment on the microbiome.
POMC-specific knockdown of Tril reduces body adiposity and increases hypothalamic leptin responsiveness
Authors: Moura-Assis Alexandre , Nogueira Pedro A. , de-Lima-Junior Jose C. , Simabuco Fernando M. , Gaspar Joana M. , Donato Jose , Velloso Licio A.
Published: June 2020

In a public dataset of transcripts differentially expressed in selected neuronal subpopulations of the arcuate nucleus, we identified TLR4-interactor with leucine-rich repeats (Tril) as a potential candidate for mediating the harmful effects of a high-fat diet in proopiomelanocortin (POMC) neurons. The non-cell-specific inhibition of Tril in the arcuate nucleus resulted in reduced hypothalamic inflammation, protection against diet-induced obesity associated with increased whole-body energy expenditure and increased systemic glucose tolerance. The inhibition of Tril, specifically in POMC neurons, resulted in a trend for protection against diet-induced obesity, increased energy expenditure and increased hypothalamic sensitivity to leptin. Thus, Tril emerges as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental diet-induced obesity.
Accessible, Reproducible, and Scalable Machine Learning for Biomedicine
Authors: Gu Qiang , Kumar Anup , Bray Simon , Creason Allison , Khanteymoori Alireza , Jalili Vahid , Grüning Björn , Goecks Jeremy
Published: June 2020

Supervised machine learning, where the goal is to predict labels of new instances by training on labeled data, has become an essential tool in biomedical data analysis. To make supervised machine learning more accessible to biomedical scientists, we have developed Galaxy-ML, a platform that enables scientists to perform end-to-end reproducible machine learning analyses at large scale using only a web browser. Galaxy-ML extends Galaxy, a biomedical computational workbench used by tens of thousands of scientists across the world, with a machine learning tool suite that supports end-to-end analysis.
Deep ancestral introgression shapes evolutionary history of dragonflies and damselflies
Authors: Suvorov Anton , Scornavacca Celine , Fujimoto M. Stanley , Bodily Paul , Clement Mark , Crandall Keith A. , Whiting Michael F. , Schrider Daniel R. , Bybee Seth M.
Published: June 2020

Introgression is arguably one of the most important biological processes in the evolution of groups of related species, affecting at least 10% of the extant species in the animal kingdom. Introgression reduces genetic divergence between species, and in some cases can be highly beneficial, facilitating rapid adaptation to ever-changing environmental pressures. Introgression also significantly impacts inference of phylogenetic species relationships where a strictly binary tree model cannot adequately explain reticulate net-like species relationships. Here we use phylogenomic approaches to understand patterns of introgression along the evolutionary history of a unique, non-model insect system: dragonflies and damselflies (Odonata). We demonstrate that introgression is a pervasive evolutionary force across various taxonomic levels within Odonata. In particular, we show that the morphologically “intermediate” species of Anisozygoptera (one of the three primary suborders within Odonata besides Zygoptera and Anisoptera), which retain phenotypic characteristics of the other two suborders, experienced high levels of introgression likely coming from zygopteran genomes. Additionally, we found evidence for multiple cases of deep inter-superfamilial ancestral introgression.
Anα-cyanostilbene derivative for the enhanced detection and imaging of amyloid fibril aggregates
Authors: Marzano Nicholas. R , Wray Kelly M , Johnston Caitlin L , Paudel Bishnu P , Hong Yuning , van Oijen Antoine , Ecroyd Heath
Published: June 2020

The aggregation of proteins into amyloid fibrils has been implicated in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Benzothiazole dyes such as Thioflavin T (ThT) are well characterised and widely used fluorescent probes for monitoring amyloid fibril formation. However, existing dyes lack sensitivity and specificity to oligomeric intermediates formed during fibril formation. In this work we describe the use of an α-cyanostilbene derivative with aggregation-induced emission properties (called ASCP) as a fluorescent probe for the detection of amyloid fibrils. Similar to ThT, ASCP is fluorogenic in the presence of amyloid fibrils and upon binding and excitation at 460 nm produces a red-shifted emission with a large Stokes shift of 145 nm. ASCP has a higher binding affinity to fibrillar α-synuclein than ThT and likely shares the same binding sites to amyloid fibrils. Importantly, ASCP was found to also be fluorogenic in the presence of amorphous aggregates and can detect oligomeric species formed early during aggregation. Moreover, ASCP can be used to visualise fibrils via Total Internal Reflection Fluorescence (TIRF) microscopy and, due to its large Stokes shift, simultaneously monitor the fluorescence emission of other labelled proteins following excitation with the same laser used to excite ASCP. Consequently, ASCP possesses enhanced and unique spectral characteristics compared to ThT that make it a promising alternative for thein vitrostudy of amyloid fibrils and the mechanisms by which they form.
Problem drinking before and during the COVID-19 crisis in US and UK adults: Evidence from two population-based longitudinal studies
Authors: Daly Michael , Robinson Eric
Published: June 2020

Background

The impact of the COVID-19 crisis on potentially harmful alcohol consumption is unclear.

Aims

To test whether the prevalence of problem drinking has changed from before to during the COVID-19 crisis in the US and UK.

Design/Setting

We examined nationally representative longitudinal data on how problem drinking has changed from pre-pandemic levels among adults in the US (N=7,327; Understanding America Study) and UK (N=12,594; UK Household Longitudinal Study).

Methods

In the US, we examined rates of consuming alcohol ≥ 4 times in the past week at baseline (March, 2020) and across four waves of follow-up (April-May, 2020). In the UK we assessed the prevalence of consuming alcohol ≥ 4 times per week and weekly heavy episodic drinking using the AUDIT-C at baseline (2017-2019) and during the COVID-19 lockdown (April, 2020). We also tested whether there were specific groups at greater risk of increased problem drinking during the pandemic.

Results

Among US adults, there was a statistically significant increase in the percentage of participants reporting drinking alcohol ≥ 4 times a week which rose significantly from 11.7% to 17.9% (53% increase, p < .001) as the COVID-19 crisis developed in the US. Among UK adults, the percentage of participants reporting drinking ≥ 4 times a week increased significantly from 14.2% to 23% (62% increase, p < .001) and heavy episodic drinking at least weekly increased significantly from 9.7% to 16.6% (71% increase, p < .001) when compared to pre-COVID-19 lockdown levels. Trends were similar across population demographics, although those aged under 50 years and higher income groups displayed the largest increases.

Conclusions

The COVID-19 crisis has been associated with substantial increases in problematic drinking in both US and UK adults.
Teach, and teach and teach: does the average citizen use masks correctly during daily activities? Results from an observational study with more than 12,000 participants
Authors: Stanislau Affonso de Araújo Evaldo , Henriques Amaral Fatima Maria Bernardes , Park Dongmin , Ceraldi Cameira Ana Paola , da Cunha Murilo Augustinho Muniz , Karl Evelyn Gutierrez , Henderson Sheila J.
Published: June 2020

COVID-19 is a new disease with no treatment and no vaccine so far. The pandemic is still growing in many areas. Among the core measures to prevent disease spread is the use of face masks. We observed 12,588 people in five Brazilian cities within the Baixada Santista metropolitan area. Even though this is densely populated region and heavily impacted by COVID-19 with a high risk population, only 45.1% of the observed population wore in face masks in a correct way, and another 15.5% simply did not use masks at all. The remainder used masks incorrectly, which is evidence of the worst scenario of people believing that they are protected when they are not. This is among the first studies, to the best of our knowledge, that measures real life compliance with face masks during this COVID-19 pandemic. It is our conclusion that it is paramount to first control the virus before allowing people back in the streets. We should not assume that people will wear masks properly. Equally important is to instruct and sensitize people on how to use face masks and why it is important.
Immunochemical analysis of the integrin expression in retinal pigment epithelial cells
Authors: Heller Janosch P , Heintz Tristan G , Kwok Jessica CF , Martin Keith R , Fawcett James W
Published: June 2020

Retinal pigment epithelial (RPE) cells have been used in disease modelling and transplantation studies in retinal diseases. Several types of RPE cells have been trialed, ranging from primary cells and immortalized cell lines to stem cell-derived RPE cells. During aging and in disease, the extracellular environment of the RPE cells changes, interfering with RPE cell adhesion. We hypothesize that this could be a key problem in transplantation studies that have reported lack of adhesion and survival of the transplanted RPE cells. Integrins are essential for the proper function of the RPE, mediating adhesion to Bruch’s membrane, and the binding and subsequent phagocytosis of photoreceptor outer segments. Variability that has been found in clinical trials might be due to the variability of cell types used and their expression profiles of surface molecules. Here, we set out to analyze integrin expression in primary rat RPE cells and in the human cell line ARPE-19 using immunochemistry. We found that both cell types express integrins to varying degrees. After long-term culturing, ARPE-19 cells resemble mature RPE cells, and increase integrin expression. We hence argue that it is important to test the properties of these cells prior to transplantation to avoid failure of adhesion and to facilitate correct function.
A flagellate-to-amoeboid switch in the closest living relatives of animals
Authors: Brunet Thibaut , Albert Marvin , Roman William , Spitzer Danielle C. , King Nicole
Published: June 2020

The evolution of different cell types was a key process of early animal evolution1–3. Two fundamental cell types, epithelial cells and amoeboid cells, are broadly distributed across the animal tree of life4,5but their origin and early evolution are unclear. Epithelial cells are polarized, have a fixed shape and often bear an apical cilium and microvilli. These features are shared with choanoflagellates – the closest living relatives of animals – and are thought to have been inherited from their last common ancestor with animals1,6,7. The deformable amoeboid cells of animals, on the other hand, seem strikingly different from choanoflagellates and instead evoke more distantly related eukaryotes, such as diverse amoebae – but it has been unclear whether that similarity reflects common ancestry or convergence8. Here, we show that choanoflagellates subjected to spatial confinement differentiate into an amoeboid phenotype by retracting their flagella and microvilli, generating blebs, and activating myosin-based motility. Choanoflagellate cell crawling is polarized by geometrical features of the substrate and allows escape from confined microenvironments. The confinement-induced amoeboid switch is conserved across diverse choanoflagellate species and greatly expands the known phenotypic repertoire of choanoflagellates. The broad phylogenetic distribution of the amoeboid cell phenotype across animals9–14and choanoflagellates, as well as the conserved role of myosin, suggests that myosin-mediated amoeboid motility was present in the life history of their last common ancestor. Thus, the duality between animal epithelial and crawling cells might have evolved from a temporal phenotypic switch between flagellate and amoeboid forms in their single-celled ancestors3,15,16.
IKBIP is a novel EMT-related biomarker and predicts poor survival in glioma
Authors: Yang Ying , Wang Jin , Xu Shihai , Lv Wen , Shi Fei , Shan Aijun
Published: June 2020

Purpose

I kappa B-interacting protein (IKBIP) in cancer has rarely been reported. This study aimed at investigating its expression pattern and biological function in brain glioma at transcriptional level.

Methods

We selected 301 glioma patients with microarray data from CGGA database and 697 glioma patients with RNAseq data from TCGA database. Transcriptome data and clinical data of 998 samples were analyzed. Statistical analysis and figure generating were performed with R language.

Results

We found that IKBIP expression showed positive correlation with WHO grade of glioma. IKBIP was increased in IDH wildtype and mesenchymal molecular subtype of glioma. Gene ontology analysis demonstrated that IKBIP was profoundly associated with extracellular matrix organization, cell-substrate adhesion and response to wounding in both pan-glioma and glioblastoma. Subsequent GSEA analysis revealed that IKBIP was particularly correlated with epithelial-to-mesenchymal transition (EMT). To further elucidate the relationship between IKBIP and EMT, we performed GSVA analysis to screen the EMT-related signaling pathways, and found that IKBIP expression was significantly associated with PI3K/AKT, hypoxia and TGF-β pathway. Moreover, IKBIP expression was found to be synergistic with key biomarkers of EMT, especially with N-cadherin, vimentin, snail, slug and TWIST1. Finally, higher IKBIP indicated significantly shorter survival for glioma patients.

Conclusions

IKBIP was associated with more aggressive phenotypes of gliomas.

Furthermore, IKBIP was significantly involved in EMT and could serve as an independent prognosticator in glioma.
Atlas and developmental dynamics of mouse DNase I hypersensitive sites
Authors: Breeze Charles E. , Lazar John , Mercer Tim , Halow Jessica , Washington Ida , Lee Kristen , Ibarrientos Sean , Castillo Andres , Neri Fidencio , Haugen Eric , Rynes Eric , Reynolds Alex , Bates Daniel , Diegel Morgan , Dunn Douglas , Kaul Rajinder , Sandstrom Richard , Meuleman Wouter , Bender M.A. , Groudine Mark , Stamatoyannopoulos John A.
Published: June 2020

Early mammalian development is orchestrated by genome-encoded regulatory elements populated by a changing complement of regulatory factors, creating a dynamic chromatin landscape. To define the spatiotemporal organization of regulatory DNA landscapes during mouse development and maturation, we generated nucleotide-resolution DNA accessibility maps from 15 tissues sampled at 9 intervals spanning post-conception day 9.5 through early adult, and integrated these with 41 adult-stage DNase-seq profiles to create a global atlas of mouse regulatory DNA. Collectively, we delineated >1.8 million DNase I hypersensitive sites (DHSs), with the vast majority displaying temporal and tissue-selective patterning. Here we show that tissue regulatory DNA compartments show sharp embryonic-to-fetal transitions characterized by wholesale turnover of DHSs and progressive domination by a diminishing number of transcription factors. We show further that aligning mouse and human fetal development on a regulatory axis exposes disease-associated variation enriched in early intervals lacking human samples. Our results provide an expansive new resource for decoding mammalian developmental regulatory programs.
3-Dimensional Magnetic Resonance Imaging of the Freely Moving Human Eye
Authors: Franceschiello Benedetta , Di Sopra Lorenzo , Minier Astrid , Ionta Silvio , Zeugin David , Notter Michael P. , Bastiaansen Jessica A.M. , Jorge João , Yerly Jérôme , Stuber Matthias , Murray Micah M.
Published: June 2020

Eye motion is a major confound for magnetic resonance imaging (MRI) in neuroscience or ophthalmology. Currently, solutions toward eye stabilisation include participants fixating or administration of paralytics/anaesthetics. We developed a novel MRI protocol for acquiring 3-dimensional images while the eye freely moves. Eye motion serves as the basis for image reconstruction, rather than an impediment. We fully reconstruct videos of the moving eye and head. We quantitatively validate data quality with millimetre resolution in two ways for individual participants. First, eye position based on reconstructed images correlated with simultaneous eye-tracking. Second, the reconstructed images preserve anatomical properties; the eye’s axial length measured from MRI images matched that obtained with ocular biometry. The technique operates on a standard clinical setup, without necessitating specialized hardware, facilitating wide deployment. In clinical practice, we anticipate that this may help reduce burden on both patients and infrastructure, by integrating multiple varieties of assessments into a single comprehensive session. More generally, our protocol is a harbinger for removing the necessity of fixation, thereby opening new opportunities for ethologically-valid, naturalistic paradigms, the inclusion of populations typically unable to stably fixate, and increased translational research such as in awake animals whose eye movements constitute an accessible behavioural readout.

Author contributions

B.F., L.D.S., M.S., and M.M.M. conceptualised the problem. B.F. and L.D.S. developed, implemented, and tested the protocol. A.M. provided optometry assessments and assisted with eye movement analysis. S.I., D.Z., and M.P.N. assisted with installation of the eye-tracking system within the MRI scanner. J.A.M.B., J.J. and J.Y. contributed with the MRI sequences and compressed sensing framework. B.F., L.D.S. and M.M.M. drafted the manuscript, and all authors contributed to internal review.

Competing interests

B.F., L.D.S., J.A.M.B., J.Y., M.S., and M.M.M. declare the following competing financial interest: a patent application for the protocol described in this manuscript has been filed (patent application: EP19160832). A.M., S.I., D.Z., M.P.N. and J.J. declare no competing financial interests.
Revisiting the intrageneric structure of the genusPseudomonaswith complete whole genome sequence information: Insights into Diversity and Host-related Genetic Determinants
Authors: Yi Buqing , Dalpke Alexander H.
Published: June 2020

Pseudomonasspp. exhibit considerable differences in host specificity and virulence. MostPseudomonasspecies were isolated exclusively from environmental sources, ranging from soil to plants, but somePseudomonasspecies have been detected from versatile sources, including both human host and environmental sources. Understanding genome variations that generate the tremendous diversity inPseudomonasbiology is important in controlling the incidence of infections. With a data set of 704Pseudomonascomplete whole genome sequences representing 186 species,Pseudomonasintrageneric structure was investigated by hierarchical clustering based on average nucleotide identity, and by phylogeny analysis based on concatenated core-gene alignment. Further comparative functional analyses indicated thatPseudomonasspecies only living in natural habitats lack multiple functions that are important in the regulation of bacterial pathogenesis, indicating the possession of these functions might be characteristic ofPseudomonashuman pathogens. Moreover, we have performed pangenome based homogeneity analyses, and detected genes with conserved structures but diversified functions across thePseudomonasgenomes, suggesting these genes play a role in driving diversity. In summary, this study provided insights into the dynamics of genome diversity and host-related genetic determinants inPseudomonas, which might help the development of more targeted antibiotics for the treatment ofPseudomonasinfections.
Prions induce minor genome-wide translational changes in neurons compared to glia
Authors: Scheckel Claudia , Imeri Marigona , Schwarz Petra , Aguzzi Adriano
Published: June 2020

Prion diseases are caused by PrPSc, a self-replicating pathologically misfolded protein that exerts toxicity predominantly in the brain. The administration of PrPSccauses a robust, reproducible and specific disease manifestation. Here we have applied a combination of translating ribosome affinity purification and ribosome profiling to identify biologically relevant prion-induced changes during disease progression in a cell-type specific and genome-wide manner. Terminally diseased mice with severe neurological symptoms showed extensive alterations in astrocytes and microglia. Surprisingly, we detected only minor changes in the translational profiles of neurons. Prion-induced alterations in glia overlapped with those identified in other neurodegenerative diseases, suggesting that similar events occur in a broad spectrum of pathologies. Our results suggest that aberrant translation within glia may suffice to cause severe neurological symptoms and may even be the primary driver of prion disease.
VAE-Sim: a novel molecular similarity measure based on a variational autoencoder
Authors: Samanta Soumitra , O’Hagan Steve , Swainston Neil , Roberts Timothy J. , Kell Douglas B.
Published: June 2020

Molecular similarity is an elusive but core ‘unsupervised’ cheminformatics concept, yet different ‘fingerprint’ encodings of molecular structures return very different similarity values even when using the same similarity metric. Each encoding may be of value when applied to other problems with objective or target functions, implying thata priorinone is ‘better’ than the others, nor than encoding-free metrics such as maximum common substructure (MCSS). We here introduce a novel approach to molecular similarity, in the form of a variational autoencoder (VAE). This learns the joint distribution p(z|x) where z is a latent vector and x are the (same) input/output data. It takes the form of a ‘bowtie’-shaped artificial neural network. In the middle is a ‘bottleneck layer’ or latent vector in which inputs are transformed into, and represented as, a vector of numbers (encoding), with a reverse process (decoding) seeking to return the SMILES string that was the input. We train a VAE on over 6 million druglike molecules and natural products (including over one million in the final holdout set). The VAE vector distances provide a rapid and novel metric for molecular similarity that is both easily and rapidly calculated. We describe the method and its application to a typical similarity problem in cheminformatics.
Comparative genomics provides an operational classification system and reveals early emergence and biased spatio-temporal distribution of SARS-CoV-2
Authors: Chiara Matteo , Horner David S. , Gissi Carmela , Pesole Graziano
Published: June 2020

Effective systems for the analysis of molecular data are of fundamental importance for real-time monitoring of the spread of infectious diseases and the study of pathogen evolution. While the Nextstrain and GISAID portals offer widely used systems for the classification of SARS-CoV-2 genomes, both present relevant limitations. Here we propose a highly reproducible method for the systematic classification of SARS-CoV-2 viral types. To demonstrate the validity of our approach, we conduct an extensive comparative genomic analysis of more than 20,000 SARS-CoV-2 genomes. Our classification system delineates 12 clusters and 4 super-clusters in SARS-CoV-2, with a highly biased spatio-temporal distribution worldwide, and provides important observations concerning the evolutionary processes associated with the emergence of novel viral types. Based on the estimates of SARS-CoV-2 evolutionary rate and genetic distances of genomes of the early pandemic phase, we infer that SARS-CoV-2 could have been circulating in humans since August-November 2019. The observed pattern of genomic variability is remarkably similar between all clusters and super-clusters, being UTRs and the s2m element, a highly conserved secondary structure element, the most variable genomic regions. While several polymorphic sites that are specific to one or more clusters were predicted to be under positive or negative selection, overall, our analyses also suggest that the emergence of novel genome types is unlikely to be driven by widespread convergent evolution and independent fixation of advantageous substitutions. While, in the absence of rigorous experimental validation, several questions concerning the evolutionary processes and the phenotypic characteristics (increased/decreased virulence) remain open, we believe that the approach outlined in this study can be of relevance for the tracking and functional characterization of different types of SARS-CoV-2 genomes.
Ambient light and mimicry as drivers of wing transparency in Lepidoptera
Authors: Arias Mónica , Barbut Jérôme , Rougerie Rodolphe , Dutry Manon , Kohler Mireia , Laulan Baptiste , Paillard Caroline , Berthier Serge , Andraud Christine , Elias Marianne , Gomez Doris
Published: June 2020

Transparency reduces prey detectability by predators. While transparent aquatic species hold higher transparency levels as the light availability of their habitat increases, less is known about such variation in terrestrial species. Lepidoptera species exhibiting transparent wings display various levels of transparency. Using two complementary approaches, we explore how the evolution of different transparency degrees relates to habitat openness, activity rhythm and mimicry syndrome (bee/wasp versus dead-leaf mimic). First, by exposing artificial moth-like prey to wild avian predators in a range of habitat openness, we show that survival is lower in more open habitats. We also found that less transparent morphs are more attacked than more transparent ones, regardless of habitat openness degree. Second, by analysing the evolution of wing features and ecological traits in 107 clearwing species, we found that diurnal species transmit more light than nocturnal species under certain conditions (when considering only forewings, at smaller clearwing surfaces and at larger wing lengths) and that species flying in open habitats and exhibiting large percentages of clearwing surface transmit slightly more light than those flying in closed habitats, although this is reversed at smaller percentages of clearwing surfaces. Additionally, bee/wasp mimics are more often diurnal and have higher and less variable light transmittances than dead-leaf mimics, which are more often nocturnal. Flying during the day, in open habitats and mimicking insects with transparent wings seem to promote high light transmittance under certain circumstances. Activity rhythm, habitat openness and species interactions play a crucial role in determining transparency design on land.
Impact of a rapid decline in malaria transmission on antimalarial IgG subclasses and avidity
Authors: Ssewanyana Isaac , Rek John , Rodriguez Isabel , Wu Lindsey , Arinaitwe Emmanuel , Nankabirwa Joaniter I , Beeson James G , Mayanja-Kizza Harriet , Rosenthal Philip J , Dorsey Grant , Kamya Moses , Drakeley Chris , Greenhouse Bryan , K.A.Tetteh Kevin
Published: June 2020

Understanding how immunity to malaria is affected by declining transmission is important to aid vaccine design and understand disease resurgence. Both IgG subclasses and avidity of antigen-specific responses are important components of an effective immune response.

Using a multiplex bead array assay, we measured the total IgG, IgG subclasses, and avidity profiles of responses to 18P. falciparumblood stage antigens in samples from 160 Ugandans collected at 2 time points during high malaria transmission and 2 time points following a dramatic reduction in transmission.

Results demonstrated that, for the antigens tested, (i) the rate of decay of total IgG following infection declined with age and was driven consistently by the decrease in IgG3 and occasionally the decrease in IgG1; (ii) the proportion of IgG3 relative to IgG1 in the absence of infection increased with age; (iii) the increase in avidity index (the strength of association between the antibody and antigen) following infection was largely due to a rapid loss of non-avid compared to avid total IgG; and (iv) both avid and non-avid total IgG in the absence of infection increased with age.

Further studies are required to understand the functional differences between IgG1 and IgG3 in order to determine their contribution to the longevity of protective immunity to malaria. Measuring changes in antibody avidity may be a better approach of detecting affinity maturation compared to avidity index due to the differential expansion and contraction of high and low avidity total IgG.
Estimation of the SNP mutation rate in two vegetatively propagating species of duckweed
Authors: Sandler George , Bartkowska Magdalena , Agrawal Aneil F. , Wright Stephen I.
Published: June 2020

Mutation rate estimates for vegetatively reproducing organisms are rare, despite their frequent occurrence across the tree of life. Here we report mutation rate estimates in two vegetatively reproducing duckweed species,Lemna minorandSpirodela polyrhiza. We use a modified approach to estimating mutation rates by taking into account the reduction in mutation detection power that occurs when new individuals are produced from multiple cell lineages. We estimate an extremely low per generation mutation rate in both species of duckweed and note that allelic coverage atde novomutation sites is very skewed. We also find no substantial difference in mutation rate between mutation accumulation lines propagated under benign conditions and those grown under salt stress. Finally, we discuss the implications of interpreting mutation rate estimates in vegetatively propagating organisms.