bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional response to host chemical cues underpins expansion of host range in a fungal plant pathogen lineage
Authors: Kusch Stefan , Larrouy Justine , Ibrahim Heba M. M. , Gasset Noémie , Navaud Olivier , Mbengue Malick , Zanchetta Catherine , Lopez-Roques Celine , Donnadieu Cecile , Raffaele Sylvain
Published: October 2020

The host range of parasites is an important factor in assessing the dynamics of disease epidemics. The evolution of pathogens to accommodate new hosts may lead to host range expansion, a process the molecular bases of which are largely enigmatic. The fungusSclerotinia sclerotiorumparasitizes more than 400 plant species from diverse eudicot families while its close relative,S. trifoliorum, is restricted to plants from theFabaceaefamily. We analyzedS. sclerotiorumglobal transcriptome reprogramming on hosts from six botanical families and reveal a flexible, host-specific transcriptional program driven by core and host-response co-expression (SPREx) gene clusters. We generated a chromosome-level genome assembly forS. trifoliorumand found near-complete gene space conservation in broad and narrow host rangeSclerotiniaspecies. However,S. trifoliorumshowed increased sensitivity to theBrassicaceaedefense compound camalexin. Inter-specific transcriptome analyses revealed a lack of transcriptional response to camalexin inS. trifoliorumand provide evidence thatcis-regulatory variation associates with the genetic accommodation ofBrassicaceaein theSclerotiniahost range. Our work demonstrates adaptive plasticity of a broad host range pathogen with specific responses to different host plants and demonstrates the co-existence of signatures for generalist and polyspecialist life styles in the genome of a plant pathogen. We reason that this mechanism enables the emergence of new disease with no or limited gene flow between strains and species, and could underlie the emergence of new epidemics originating from wild plants in agricultural settings.
Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients
Authors: Ren Xianwen , Wen Wen , Fan Xiaoying , Hou Wenhong , Su Bin , Cai Pengfei , Li Jiesheng , Liu Yang , Tang Fei , Zhang Fan , Yang Yu , He Jiangping , Ma Wenji , He Jingjing , Wang Pingping , Cao Qiqi , Chen Fangjin , Chen Yuqing , Cheng Xuelian , Deng Guohong , Deng Xilong , Ding Wenyu , Feng Yingmei , Gan Rui , Guo Chuang , Guo Weiqiang , He Shuai , Jiang Chen , Liang Juanran , Li Yi-min , Lin Jun , Ling Yun , Liu Haofei , Liu Jianwei , Liu Nianping , Liu Yang , Luo Meng , Ma Qiang , Song Qibing , Sun Wujianan , Wang GaoXiang , Wang Feng , Wang Ying , Wen Xiaofeng , Wu Qian , Xu Gang , Xie Xiaowei , Xiong Xinxin , Xing Xudong , Xu Hao , Yin Chonghai , Yu Dongdong , Yu Kezhuo , Yuan Jin , Zhang Biao , Zhang Tong , Zhao Jincun , Zhao Peidong , Zhou Jianfeng , Zhou Wei , Zhong Sujuan , Zhong Xiaosong , Zhang Shuye , Zhu Lin , Zhu Ping , Zou Bin , Zou Jiahua , Zuo Zengtao , Bai Fan , Huang Xi , Bian Xiuwu , Zhou Penghui , Jiang Qinghua , Huang Zhiwei , Bei Jin-Xin , Wei Lai , Liu Xindong , Cheng Tao , Li Xiangpan , Zhao Pingsen , Wang Fu-Sheng , Wang Hongyang , Su Bing , Zhang Zheng , Qu Kun , Wang Xiaoqun , Chen Jiekai , Jin Ronghua , Zhang Zemin
Published: October 2020

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.

HIGHLIGHTS

Large-scale scRNA-seq analysis depicts the immune landscape of COVID-19

Lymphopenia and active T and B cell responses coexist and are shaped by age and sex

SARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responses

Cytokine storms with systemic S100A8/A9 are associated with COVID-19 severity
Gender stereotype and the scientific career of women: Evidence from biomedical research centers
Authors: Montalvo Jose G. , Alimonti Daniele , Reiland Sonja , Vernos Isabelle
Published: October 2020

Women are underrepresented in the top ranks of the scientific career, including the biomedical disciplines. This is not generally the result of explicit and easily recognizable gender biases but the outcome of decisions with many components of unconscious nature that are difficult to assess. Evidence suggests that implicit gender stereotypes influence perceptions as well as decisions. To explore these potential reasons of women’s underrepresentation in life sciences we analyzed the outcome of gender-science and gender-career Implicit Association Tests (IAT) taken by 2,589 scientists working in high profile biomedical research centers. We found that male-science association is less pronounced among researchers than in the general population (34% below the level of the general population). However, this difference is mostly explained by the low level of the IAT score among female researchers. Despite the highly meritocratic view of the academic career, male scientists have a high level of male-science association (261% the level among women scientists), similar to the general population.
Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19
Authors: Saris Anno , Reijnders Tom D.Y. , Nossent Esther J. , Schuurman Alex R. , Verhoeff Jan , van Asten Saskia D. , Bontkes Hetty J. , Blok Siebe G. , Duitman Janwillem , Bogaard Harm Jan , Heunks Leo , Lutter Rene , van der Poll Tom , Garcia Vallejo Juan J. ,   on behalf of the ArtDECO consortium and the Amsterdam UMC COVID study group
Published: October 2020

Our understanding of the coronavirus disease-19 (COVID-19) immune response is almost exclusively derived from studies that examined blood. To gain insight in the pulmonary immune response we analysed BALF samples and paired blood samples from 17 severe COVID-19 patients. Macrophages and T cells were the most abundant cells in BALF. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells and expressed higher levels of the exhaustion marker PD-1 than in peripheral blood. Prolonged ICU stay associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma. In conclusion, the bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood.

The bronchoalveolar immune response in severe COVID-19 strongly differs from the peripheral blood immune profile. Fatal COVID-19 associated with T cell activation blood, but not in BALF.
BIO-LGCA: a cellular automaton modelling class for analysing collective cell migration
Authors: Deutsch Andreas , Nava-Sedeño Josué Manik , Syga Simon , Hatzikirou Haralampos
Published: October 2020

1

Collective dynamics in multicellular systems such as biological organs and tissues plays a key role in biological development, regeneration, and pathological conditions. Collective tissue dynamics - understood as population behaviour arising from the interplay of the constituting discrete cells - can be studied with on- and off-lattice agent-based models. However, classical on-lattice agent-based models, also known as cellular automata, fail to replicate key aspects of collective migration, which is a central instance of collective behaviour in multicellular systems.

To overcome drawbacks of classical on-lattice models, we introduce an on-lattice, agent-based modelling class for collective cell migration, which we call biological lattice-gas cellular automaton (BIO-LGCA). The BIO-LGCA is characterised by synchronous time updates, and the explicit consideration of individual cell velocities. While rules in classical cellular automata are typically chosen ad hoc, rules for cell-cell and cell-environment interactions in the BIO-LGCA can also be derived from experimental cell migration data or biophysical laws for individual cell migration. We introduce elementary BIO-LGCA models of fundamental cell interactions, which may be combined in a modular fashion to model complex multicellular phenomena. We exemplify the mathematical mean-field analysis of specific BIO-LGCA models, which allows to explain collective behaviour. The first example predicts the formation of clusters in adhesively interacting cells. The second example is based on a novel BIO-LGCA combining adhesive interactions and alignment. For this model, our analysis clarifies the nature of the recently discovered invasion plasticity of breast cancer cells in heterogeneous environments. A Python package which implements various interaction rules and visualisations of BIO-LGCA model simulations we have developed is available athttps://github.com/sisyga/BIO-LGCA.

2

Author summary

Pattern formation during embryonic development and pathological tissue dynamics, such as cancer invasion, emerge from individual inter-cellular interactions. In order to study the impact of single cell dynamics and cell-cell interactions on tissue behaviour, one needs to develop space-time-dependent on- or off-lattice agent-based models (ABMs), which consider the behaviour of individual cells. However, classical on-lattice agent-based models also known as cellular automata fail to replicate key aspects of collective migration, which is a central instance of collective behaviour in multicellular systems. Here, we present the rule- and lattice-based BIO-LGCA modelling class which allows for (i) rigorous derivation of rules from biophysical laws and/or experimental data, (ii) mathematical analysis of collective migration, and (iii) computationally efficient simulations.
Prednisolone rescues Duchenne Muscular Dystrophy phenotypes in human pluripotent stem cells-derived skeletal musclein vitro
Authors: Tanoury Ziad Al , Zimmermann John F. , Rao Jyoti , Sieiro Daniel , McNamara Harry , Cherrier Thomas , Hick Aurore , Bousson Fanny , Fugier Charlotte , Marchiano Fabio , Habermann Bianca , Chal Jérome , Nesmith Alexander P. , Gapon Svetlana , Wagner Erica , Bassel-Duby Rhonda , Olson Eric , Cohen Adam E. , Parker Kevin Kit , Pourquié Olivier
Published: October 2020

Duchenne Muscular Dystrophy (DMD) is a devastating genetic disease leading to degeneration of skeletal muscles and premature death. How dystrophin absence leads to muscle wasting remains unclear. Here, we describe an optimized protocol to differentiate human induced Pluripotent Stem Cells (iPSC) to a late myogenic stage. This allows to recapitulate classical DMD phenotypes (mislocalization of proteins of the Dystrophin-glycoprotein associated complex (DGC), increased fusion, myofiber branching, force contraction defects and calcium hyperactivation) in isogenic DMD-mutant iPSC linesin vitro. Treatment of the myogenic cultures with prednisolone (the standard of care for DMD) can dramatically rescue force contraction, fusion and branching defects in DMD iPSC lines. This argues that prednisolone acts directly on myofibers, challenging the largely prevalent view that its beneficial effects are due to anti-inflammatory properties. Our work introduces a new humanin vitromodel to study the onset of DMD pathology and test novel therapeutic approaches.
Rules of nature’sFormula Run: Muscle mechanics during late stance is the key to explaining maximum running speed
Authors: Günther Michael , Rockenfeller Robert , Weihmann Tom , Haeufle Daniel F. B. , Götz Thomas , Schmitt Syn
Published: October 2020

The maximum running speed of legged animals is one evident factor for evolutionary selection—for predators and prey. Therefore, it has been studied across the entire size range of animals, from the smallest mites to the largest elephants, and even beyond to extinct dinosaurs. A recent analysis of the relation between animal mass (size) and maximum running speed showed that there seems to be an optimal range of body masses in which the highest terrestrial running speeds occur. However, the conclusion drawn from that analysis—namely, that maximum speed is limited by the fatigue of white muscle fibres in the acceleration of the body mass to some theoretically possible maximum speed—was based on coarse reasoning on metabolic grounds, which neglected important biomechanical factors and basic muscle-metabolic parameters. Here, we propose a generic biomechanical model to investigate the allometry of the maximum speed of legged running. The model incorporates biomechanically important concepts: the ground reaction force being counteracted by air drag, the leg with its gearing of both a muscle into a leg length change and the muscle into the ground reaction force, as well as the maximum muscle contraction velocity, which includes muscle-tendon dynamics, and the muscle inertia—with all of them scaling with body mass. Put together, these concepts’ characteristics and their interactions provide a mechanistic explanation for the allometry of maximum legged running speed. This accompanies the offering of an explanation for the empirically found, overall maximum in speed: In animals bigger than a cheetah or pronghorn, the time that any leg-extending muscle needs to settle, starting from being isometric at about midstance, at the concentric contraction speed required for running at highest speeds becomes too long to be attainable within the time period of a leg moving from midstance to lift-off. Based on our biomechanical model we, thus, suggest considering the overall speed maximum to indicate muscle inertia being functionally significant in animal locomotion. Furthermore, the model renders possible insights into biological design principles such as differences in the leg concept between cats and spiders, and the relevance of multi-leg (mammals: four, insects: six, spiders: eight) body designs and emerging gaits. Moreover, we expose a completely new consideration regarding the muscles’ metabolic energy consumption, both during acceleration to maximum speed and in steady-state locomotion.
Is the radial growth of irrigated urban trees more strongly correlated to light and temperature than water?
Authors: Griffin Kevin L. , Harris Thomas G. , Bruner Sarah , McKenzie Patrick , Hise Jeremy
Published: October 2020

Background

Real-time monitoring of tree growth can provide novel information about trees in urban/suburban areas and the myriad ecosystem services they provide. By monitoring irrigated specimen trees we test the hypothesis that in trees with sufficient water, growth is governed by environmental factors regulating energy gain rather than by factors related to water use.

Methods

Internet enabled, high-resolution dendrometers were installed on three trees in Southampton, NY. The instruments, along with a weather station, streamed data to a project web page that was updated once an hour. (https://ecosensornetwork.com). Growing periods were determined using a Hidden Markov Model based on Zweifel et al.’s (2016) zero-growth model. Linear models and conditional inference trees correlated environmental variables to growth magnitude and rate of growth.

Results

Growth was governed by the interacting environmental variables of air temperature, soil moisture, VPD and took place primarily at night. Radial growth of spruce began April 14 after the accumulation of 69.7 °C growing degrees days and ended September 7th. Cedar growth began later (April 26th), after the accumulation of 160.6 °C and ended later (November 3rd). During the observation period, these three modest suburban trees sequestered 108.3 kg of CO2.

Conclusions

Though irrigated, residential tree growth in our experiment was affected by environmental factors relating to both water use and energy gain through photosynthesis. Linking tree growth to fluctuations in environmental conditions facilitates the development of a predictive understanding useful for ecosystem management and growth forecasting across future altering climates.
Altering CLC stoichiometry by reducing non-polar side-chains at the dimerization interface
Authors: Mersch Kacey , Ozturk Tugba N. , Park Kunwoong , Lim Hyun-Ho , Robertson Janice L.
Published: October 2020

CLC-ec1 is a Cl-/H+antiporter that forms stable homodimers in lipid bilayers, with a free energy of −10.9 kcal/mole relative to the 1 subunit/lipid standard state in 2:1 POPE/POPG lipid bilayers. The dimerization interface is formed by four transmembrane helices: H, I, P and Q, that are lined by non-polar side-chains that come in close contact, yet it is unclear as to whether their interactions drive dimerization. To investigate whether non-polar side-chains are required for dimer assembly, we designed a series of constructs where side-chain packing in the dimer state is significantly reduced by making 4-5 alanine substitutions along each helix (H-ala, I-ala, P-ala, Q-ala). All constructs are functional and three purify as stable dimers in detergent micelles despite the removal of significant side-chain interactions. On the other hand, H-ala shows the unique behavior of purifying as a mixture of monomers and dimers, followed by a rapid and complete conversion to monomers. In lipid bilayers, all four constructs are monomeric as examined by single-molecule photobleaching analysis. Further study of the H-helix shows that the single mutation L194A is sufficient to yield monomeric CLC-ec1 in detergent micelles and lipid bilayers. X-ray crystal structures of L194A reveal the protein re-assembles to form dimers, with a structure that is identical to wild-type. Altogether, these results demonstrate that non-polar membrane embedded side-chains play an important role in defining dimer stability, but the stoichiometry is highly contextual to the solvent environment. Furthermore, we discovered that L194 is a molecular hot-spot for defining dimerization of CLC-ec1.
Non-canonical Activation of Human Group 2 Innate Lymphoid Cells by TLR4 Signaling
Authors: She Li , Alanazi Hamad H. , Wang Jingwei , Chupp Daniel P. , Xu Yijiang , Zan Hong , Xu Zhenming , Sun Yilun , Xiong Na , Zhang Nu , Zhang Xin , Liu Yong , Li Xiao-Dong
Published: October 2020

Group 2 innate lymphoid cells (ILC2) are emerging as a critical player in type 2 immunity at barrier sites in response to microbial infections and allergen exposures. Although their classical activators are known to be host epithelial-derived alarmin cytokines IL-33, IL-25 or TSLP, it remains elusive whether ILC2 cells can be activated by directly sensing microbial ligands via pattern-recognition receptors such as toll-like receptors (TLRs). Here we report that toll-like receptor 4 (TLR4) is a potent activating receptor of human ILC2. We found that among many microbial ligands examined, lipopolysaccharides (LPS) from multiple species of Gram-negative bacteria, was found to potently stimulate human, but not murine ILC2, to proliferate and produce massive amounts of type 2 effector cytokines IL-4, IL-5, and IL-13. LPS-activated ILC2 also had greatly enhanced the CD40 ligand (CD154) expression and were able to promote the proliferation and antibody production of human B cells in culture. In a humanized mouse model, LPS activated the adoptively transferred human ILC2 in mouse lungs. Both NF-kB and JAK pathways, but not the IL-33-ST2 pathway, were required for LPS to activate human ILC2. RNA-seq data further revealed that LPS induced a large set of genes overlapped significantly with those induced by IL-33. Collectively, these findings support a non-classical mode of activating human ILC2 cells via the LPS-TLR4 signaling axis. Thus, targeting TLR4 signaling pathway might be developed as a new approach by modulating ILC2 activation in treating various type 2 immunity-associated diseases.
A prospective longitudinal study shows putamen volume is associated with moderate amphetamine use and resultant cognitive impairments
Authors: Kendrick Keith M , Daumann Joerg , Wagner Daniel , Koester Philip , Tittgemeyer Marc , Luo Qiang , Gouzoulis-Mayfrank Euphrosyne , Becker Benjamin
Published: October 2020

Background

Amphetamine-type stimulants (ATS) have become a critical public health issue. Animal models have indicated a clear neurotoxic potential of ATSs. In humans, chronic use has been associated with cognitive deficits and structural brain abnormalities. However, cross-sectional retrospective designs in chronic users cannot truly determine the causal direction of the effects.

Methods

In a prospective-longitudinal study design cognitive functioning and brain structure were assessed at baseline and at 12-months follow-up in occasional ATS users (cumulative lifetime use <10 units at baseline).

Results

Examination of change-scores between the initial examination and follow-up revealed declined verbal memory performance and putamen volume in users with high relative to low interim ATS exposure. In the entire sample interim ATS use, memory decline and putamen volume reductions were strongly associated.

Conclusions

The present findings support the hypothesis that ATS use is associated with deficient dorsal striatal morphology which might reflect alterations in dopaminergic pathways. More importantly, these findings strongly suggest that even occasional, low-dose ATS use disrupts striatal integrity and cognitive functioning.
Supervised Application of Internal Validation Measures to Benchmark Dimensionality Reduction Methods in scRNA-seq Data
Authors: Koch Forrest C , Sutton Gavin J , Voineagu Irina , Vafaee Fatemeh
Published: October 2020

A typical single-cell RNA sequencing (scRNA-seq) experiment will measure on the order of 20,000 transcripts and thousands, if not millions, of cells. The high dimensionality of such data presents serious complications for traditional data analysis methods and, as such, methods to reduce dimensionality play an integral role in many analysis pipelines. However, few studies benchmark the performance of these methods on scRNA-seq data, with existing comparisons assessing performance via downstream analysis accuracy measures which may confound the interpretation of their results. Here, we present the most comprehensive benchmark of dimensionality reduction methods in scRNA-seq data to date, utilizing over 300,000 compute hours to assess the performance of over 25,000 low dimension embeddings across 33 dimensionality reduction methods and 55 scRNA-seq datasets (ranging from 66-27,500 cells). We employ a simple-yet-novel approach which does not rely on the results of downstream analyses. Internal validation measures (IVMs), traditionally used as an unsupervised method to assess clustering performance, are repurposed to measure how well-formed biological clusters are after dimensionality reduction. Performance was further evaluated using nearly 200,000,000 iterations of DBSCAN, a density-based clustering algorithm, showing that hyperparameter optimization using IVMs as the objective function leads to near-optimal clustering. Methods were also assessed on the extent to which they preserve the global structure of the data, and on their computational memory and time requirements across a large range of sample sizes. Our comprehensive benchmarking analysis provides a valuable resource for researchers and aims to guide best practice for dimensionality reduction in scRNA-seq analyses, and we highlight LDA (Latent Dirichlet Allocation) and PHATE (Potential of Heat-diffusion for Affinity-based Transition Embedding) as high-performing algorithms.
Comparative transcriptomic analysis reveals conserved transcriptional programs underpinning organogenesis and reproduction in land plants
Authors: Julca Irene , Ferrari Camilla , Flores-Tornero María , Proost Sebastian , Lindner Ann-Cathrin , Hackenberg Dieter , Steinbachová Lenka , Michaelidis Christos , Pereira Sónia Gomes , Misra Chandra Shekhar , Kawashima Tomokazu , Borg Michael , Berger Frédéric , Goldberg Jacob , Johnson Mark , Honys David , Twell David , Sprunck Stefanie , Dresselhaus Thomas , Becker Jörg D. , Mutwil Marek
Published: October 2020

The evolution of plant organs, including leaves, stems, roots, and flowers, mediated the explosive radiation of land plants, which shaped the biosphere and allowed the establishment of terrestrial animal life. Furthermore, the fertilization products of angiosperms, seeds serve as the basis for most of our food. The evolution of organs and immobile gametes required the coordinated acquisition of novel gene functions, the co-option of existing genes, and the development of novel regulatory programs. However, our knowledge of these events is limited, as no large-scale analyses of genomic and transcriptomic data have been performed for land plants. To remedy this, we have generated gene expression atlases for various organs and gametes of 10 plant species comprising bryophytes, vascular plants, gymnosperms, and flowering plants. Comparative analysis of the atlases identified hundreds of organ- and gamete-specific gene families and revealed that most of the specific transcriptomes are significantly conserved. Interestingly, the appearance of organ-specific gene families does not coincide with the corresponding organ’s appearance, suggesting that co-option of existing genes is the main mechanism for evolving new organs. In contrast to female gametes, male gametes showed a high number and conservation of specific genes, suggesting that male reproduction is highly specialized. The expression atlas capturing pollen development revealed numerous transcription factors and kinases essential for pollen biogenesis and function. To provide easy access to the expression atlases and these comparative analyses, we provide an online database,www.evorepro.plant.tools, that allows the exploration of expression profiles, organ-specific genes, phylogenetic trees, co-expression networks, and others.
Elevated temperatures drive the evolution of armor loss in the threespine sticklebackGasterosteus aculeatus
Authors: Smith Carl , Zięba Grzegorz , Przybylski Mirosław
Published: October 2020

While there is evidence of genetic and phenotypic responses to climate change, few studies have demonstrated change in functional traits with a known genetic basis. Here we present evidence for an evolutionary adaptive response to elevated temperatures in freshwater populations of the threespine stickleback (Gasterosteus aculeatus). Using a unique set of historical data and museum specimens, in combination with contemporary samples, we fitted a Bayesian spatial model to identify a population-level decline in the number of lateral bony plates, comprising anti-predator armor, in multiple populations of sticklebacks over the last 90 years in Poland. Armor loss was predicted by elevated temperatures and is proposed to be a correlated response to selection for reduced body size. This study demonstrates a change in a functional trait of known genetic basis in response to elevated temperature, and illustrates the utility of the threespine stickleback as a model for measuring the evolutionary and ecological impacts of environmental change across the northern hemisphere.
Stromal Oncostatin M axis promotes breast cancer progression
Authors: Araujo Angela M. , Abaurrea Andrea , Azcoaga Peio , López-Velazco Joanna I. , Rezola Ricardo , Osorio-Querejeta Iñaki , Valdés-Mora Fátima , Flores Juana M. , Jenkins Liam , Fernández-Nogueira Patricia , Ferrari Nicola , Martín-Martín Natalia , Tzankov Alexandar , Eppenberger-Castori Serenella , Alvarez-Lopez Isabel , Urruticoechea Ander , Bragado Paloma , Coleman Nicholas , Carracedo Arkaitz , Gallego-Ortega David , Calvo Fernando , Isacke Clare M. , Caffarel Maria M. , Lawrie Charles H.
Published: October 2020

Cancer cells are constantly communicating with the surrounding tumour microenvironment (TME) and they hijack physiological cell interactions to overcome immune system surveillance and promote cancer progression1,2. However, the contribution of stromal cells to the reprogramming of the TME is not well understood. In this study we provide unprecedented evidence of the role of the cytokine Oncostatin M (OSM) as central node for multicellular interactions between immune and non-immune stroma and the epithelial compartment. We show that stromal expression of the OSM:Oncostatin M Receptor (OSMR) axis plays a key role in breast cancer progression. OSMR deletion in a multistage breast cancer model delays tumour onset, tumour growth and reduces metastatic burden. We ascribed causality to the stromal function of OSM axis by demonstrating reduced tumour burden of syngeneic tumours implanted in mice. Single-cell and bioinformatic analysis of murine and human breast tumours revealed that the expression of OSM signalling components is compartmentalized in the tumour stroma. OSM expression is restricted to myeloid cells, whereas OSMR expression is detected predominantly in fibroblasts and, to a lower extent, cancer cells. Myeloid-derived OSM reprograms fibroblasts to a more contractile and pro-tumorigenic phenotype, elicits the secretion of VEGF and pro-inflammatory chemokines (e.g. CXCL1 and CXCL16), leading to increased neutrophil and macrophage recruitment. In summary, our work sheds light on the mechanism of immune regulation by the tumour microenvironment, and supports that targeting OSM:OSMR interactions is a potential therapeutic strategy to inhibit tumour-promoting inflammation and breast cancer progression.
Metabarcoding faecal samples to investigate spatiotemporal variation in the diet of the endangered Westland petrel (Procellaria westlandica)
Authors: Querejeta Marina , Lefort Marie-Caroline , Bretagnolle Vincent , Boyer Stéphane
Published: October 2020

As top predators, seabirds can be indirectly impacted by climate variability and commercial fishing activities through changes in marine communities. However, high mobility and foraging behaviour enables seabirds to exploit prey distributed patchily in time and space. This capacity to adapt to environmental change can be described through the study of their diet. Traditionally, the diet of seabirds is assessed through the morphological identification of prey remains in regurgitates. This sampling method is invasive for the bird and limited in terms of taxonomic resolution. However, the recent progress in DNA-based approaches is now providing a non-invasive means to more comprehensively and accurately characterize animal diets. Here, we used a non-invasive metabarcoding approach to characterize the diet of the Westland petrel (Procellaria westlandica), which is an endangered burrowing species, endemic to the South Island of New Zealand. We collected 99 fresh faecal samples at two different seasons and in two different sub-colonies. Our aims were to describe the diet of the Westland petrel, investigate seasonal and spatial variation in the petrels’ diet, and assess potential impacts of the New Zealand fishery industry. We found that amphipods were the most common prey, followed by cephalopods and fish. Our results could be the result of natural foraging behaviour, but also suggest a close link between the composition of prey items and New Zealand’s commercial fishing activities. In particular, the high abundance of amphipods could be the result of Westland petrels feeding on discarded fisheries waste (fish guts). Our results also showed significant differences in diet between seasons (before hatching vs chick-rearing season) and between sampling sites (two sub-colonies 1.5 km apart), indicating plasticity in the foraging strategy of the Westland petrel. Due to its non-invasive nature, metabarcoding of faecal samples can be applied to large numbers of samples to help describe dietary variation in seabirds and indicate their ecological requirements. In our example, dietary DNA (dDNA) provided valuable information regarding the dietary preferences of an iconic species in New Zealand’s unique biodiversity. dDNA can thus inform the conservation of endangered or at-risk species that have elusive foraging behaviours.
Determinants of different facets of beta diversity in Mediterranean marine amphipods
Authors: Bellisario Bruno , Camisa Federica , Abbattista Chiara , Cimmaruta Roberta
Published: October 2020

Relying on a purely taxonomic view of diversity may ignore the fact that ecological communities can be constituted of species having both distinct evolutionary histories and functional characteristics. Thus, considering how the multiple facets of diversity vary along environmental and geographic gradients may provide insights into the role of historic processes and current environmental conditions in determining the distribution of species, lineages and functions across space. By using distributional, taxonomic-distance and traits information, we explore the role of spatial/environmental gradients and of biogeographic subdivision of Mediterranean Sea on the different facets of beta diversity components in seagrass amphipods. Beta diversity partitioning and correlation analyses showed a nearly equal contribution of the replacement and richness components on total beta diversity for all facets, although the influence of environmental and geographic distance differs among components. While the replacement was mainly related to a pure spatial gradient, both the environmental and geographic distance were correlated with the richness component of beta diversities. Our results are in line with the complex paleobiogeographic history of the Mediterranean Sea, with the replacement component likely to be related to the progressive substitution of species of Atlantic origin with Mediterranean endemics along the west-east geographic gradient, and the richness component to the marked environmental difference between different basins. Moreover, the influence of biogeographic partition on the richness components suggests the role of spatially structured gradients at biogeographic level in determining the net loss/gain of species, lineages and functions, possibly influencing the assembly processes of passive dispersal organisms.
Assessment of transparency indicators across the biomedical literature: how open is open?
Authors: Serghiou Stylianos , Contopoulos-Ioannidis Despina G. , Boyack Kevin W. , Riedel Nico , Wallach Joshua D. , Ioannidis John P. A.
Published: October 2020

Recent concerns about the reproducibility of science have led to several calls for more open and transparent research practices and for the monitoring of potential improvements over time. However, with tens of thousands of new biomedical articles published per week, manually mapping and monitoring changes in transparency is unrealistic. We present an open-source, automated approach to identify five indicators of transparency (data sharing, code sharing, conflicts of interest disclosures, funding disclosures and protocol registration) and apply it across the entire open access biomedical literature of 2.75 million articles on PubMed Central. Our results indicate remarkable improvements in some (e.g. conflict of interest disclosures, funding disclosures), but not other (e.g. protocol registration, code sharing) areas of transparency over time, and map transparency across fields of science, countries, journals and publishers. This work has enabled the creation of a large, integrated, and openly available database to expedite further efforts to monitor, understand and promote transparency and reproducibility in science.
Transcriptome analysis in the maize-Ustilago maydisinteraction identifies maize-line-specific activity of fungal effectors
Authors: Schurack S , Depotter JRL , Gupta D , Thines M , Doehlemann G
Published: October 2020

The biotrophic pathogenUstilago maydiscauses smut disease on maize (Zea mays) and induces the formation of tumours on all aerial parts of the plant. Unlike in other biotrophic interactions, no gene-for-gene interactions have been identified in the maize-U. maydispathosystem. Thus, maize resistance toU. maydisis considered a polygenic, quantitative trait. Here, we study the molecular mechanisms of quantitative disease resistance (QDR) in maize, and howU. maydisinterferes with its components. Based on quantitative scoring of disease symptoms in 26 maize lines, we performed an RNA-Seq analysis of sixU. maydis-infected maize lines of highly distinct resistance levels. In accordance with the complex nature of QDR, the different maize lines showed specific responses of diverse cellular processes toU. maydisinfection. On the pathogen side, our analysis identified 406U. maydisgenes being differentially expressed between maize lines, of which 102 encode predicted effector proteins. Based on this analysis, we generatedU. maydisCRISPR/Cas9 knockout mutants for selected candidate effector sets. Infections of different maize lines with the fungal mutants and subsequent RNA-sequencing identified effectors with quantitative, maize-line-specific virulence functions, and revealed auxin-related processes as a possible target for one of them. Thus, we show that both transcriptional activity and virulence function of fungal effector genes are modified according to the infected maize line, providing new insights into the molecular mechanisms underlying QDR in the maize-U. maydisinteraction.
Impact of explicit area scaling on kinetic models involving multiple compartments
Authors: Holzheu Pascal , Großeholz Ruth , Kummer Ursula
Published: October 2020

Background

Computational modelling of cell biological processes is a frequently used technique to analyse the underlying mechanisms and to generally understand the behaviour of these processes in the context of a pathway, network or even the whole cell. The most common technique in this context is the usage of ordinary differential equations (ODEs) that describe the kinetics of the relevant processes in mechanistic detail. Here, it is usually assumed that the content of the cell is well-stirred and thus homogeneous - which is of course an over-simplification, but often worked in the past. However, many processes happen at membranes and thus not in 3D, but in 2D. The scaling of the rates of these processes poses a special problem, if volumes of compartments are changed. They will typically scale with an area, but not with the volume of the involved compartment. However, commonly, this is neglected when setting up models and/or volume scaling also sometimes automatically happens when using modelling software in the field.

Results

Here, we investigate generic as well as specific, realistic cases to find out, how strong the impact of the wrong scaling is for the outcome of simulations. We show that the importance of correct area scaling depends on the architecture of the reaction site and its changes upon volume alterations and it is hard to foresee, if it has a significant impact or not just by looking at the original model set-up. Moreover, scaled rates might exhibit more or less control over the behaviour of the system and therefore, accordingly, incorrect scaling will have more or less influence.

Conclusions

Working with multi-compartment reactions requires a careful consideration of the correct scaling of the rates when changing the volumes of the involved compartments. The error following incorrect scaling - often done by scaling with the volume of the respective compartments can lead to significant aberrations of model behaviour.
Increasing Grain Yield in Bread Wheat (Triticum aestivumL.) by Selection for High Spike Fertility Index
Authors: Pontaroli Ana Clara , Alonso María Pía , Mirabella Nadia Estefania , Panelo Juan Sebastián , Franco María Fiorella , Sebastián Vanzetti Leonardo , Lorenzo Máximo
Published: October 2020

Spike fertility index (SF) has been proposed as a promising selection criterion for increasing grain yield (GY) in bread wheat. Here, changes in GY and related traits after simulated selection (10% intensity) for high SF or high GYper sewere assessed in two RIL populations: (I) Avalon/Glupro and (II) Baguette 10/Klein Chajá, and in (III) advanced lines from a breeding program. Grain yield, SF, grain number per unit area (GN), grain weight (GW), test weight (TW) and grain protein content (GPC) were determined. Regardless of the environmental conditions, simulated selection for high SF always resulted in GN increases (between 1.6 and 27.4%). Average GY increase observed after selection for high SF (11.5%; N=10; SEM=5.8) did not differ (p=0.92) from the average GY increase observed after selection for GYper se(11.8%; N=10; SEM=4.9). Grain weight, GPC and TW tended to decrease with selection for high SF; however, these trade-offs might be avoided by concurrent selection. Our findings validate the use of SF as a selection criterion for increasing grain yield in bread wheat.
Correlative all-optical quantification of mass density and mechanics of sub-cellular compartments with fluorescence specificity
Authors: Schlüßler Raimund , Kim Kyoohyun , Nötzel Martin , Taubenberger Anna , Abuhattum Shada , Beck Timon , Müller Paul , Maharana Shovamayee , Cojoc Gheorghe , Girardo Salvatore , Hermann Andreas , Alberti Simon , Guck Jochen
Published: October 2020

Quantitative measurements of physical parameters become increasingly important for understanding biological processes. Brillouin microscopy (BM) has recently emerged as one technique providing the 3D distribution of viscoelastic properties inside biological samples — so far relying on the implicit assumption that refractive index (RI) and density can be neglected. Here, we present a novel method (FOB microscopy) combining BM with optical diffraction tomography and epi-fluorescence imaging for explicitly measuring the Brillouin shift, RI and absolute density with specificity to fuorescently labeled structures. We show that neglecting the RI and density might lead to erroneous conclusions. Investigating the nucleoplasm of wild-type HeLa cells, we find that it has lower density but higher longitudinal modulus than the cytoplasm. Thus, the longitudinal modulus is not merely sensitive to the water content of the sample — a postulate vividly discussed in the field. We demonstrate the further utility of FOB on various biological systems including adipocytes and intracellular membraneless compartments. FOB microscopy can provide unexpected scientific discoveries and shed quantitative light on processes such as phase separation and transition inside living cells.
Genome-Wide Architecture of Adaptation in Experimentally EvolvedDrosophila
Authors: Barter Thomas T. , Greenspan Zachary S. , Phillips Mark A. , Ranz José M. , Rose Michael R. , Mueller Laurence D.
Published: October 2020

The molecular basis of adaptation remains elusive even with the current ease of sequencing the genome and transcriptome. We used experimentally evolved populations ofDrosophilain conjunction with statistical learning tools to explore interactions between the genome, the transcriptome, and phenotypes. Our results indicate that transcriptomic measures from adult samples can predict phenotypic characters at many adult ages. Importantly, when comparing the genome and transcriptome in predicting phenotypic characters, we find that the two types of data are comparably useful. When using genome sites as predictors for the expression of the transcriptome, we find that gene expression is influenced by genomic regions across all large chromosome arms. Conversely, we found many genomic regions influencing the expression of numerous genes, which is consistent with widespread pleiotropy. Our results also highlight the power of the combination of experimental evolution, next-generation sequencing, and statistical learning tools in exploring the molecular basis of adaptation.
Macrophages orchestrate the expansion of a pro-angiogenic perivascular niche during cancer progression
Authors: Opzoomer James W. , Anstee Joanne E. , Dean Isaac , Hill Emily J. , Bouybayoune Ihssane , Caron Jonathan , Muliaditan Tamara , Gordon Peter , Sosnowska Dominika , Nuamah Rosamond , Pinder Sarah E. , Ng Tony , Dazzi Francesco , Kordasti Shahram , Withers David R. , Lawrence Toby , Arnold James N.
Published: October 2020

Tumor associated macrophages (TAMs) are a highly plastic stromal cell type which support cancer progression. Using single-cell RNA-sequencing of TAMs from a spontaneous murine model of mammary adenocarcinoma (MMTV-PyMT) we characterize a subset of these cells expressing lymphatic vessel endothelial hyaluronic acid receptor 1 (Lyve-1) which spatially reside proximal to blood vasculature. We demonstrate that Lyve-1+TAMs support tumor growth and identify a pivotal role for these cells in maintaining a population of perivascular mesenchymal cells which express alpha-smooth muscle actin and phenotypically resemble pericytes. Using photolabeling techniques show that mesenchymal cells maintain their prevalence in the growing tumor through proliferation and uncover a role for Lyve-1+TAMs in orchestrating a selective platelet-derived growth factor-CC-dependent expansion of the perivascular mesenchymal population, creating a pro-angiogenic niche. This study highlights the inter-reliance of the immune and non-immune stromal network which support cancer progression and provides therapeutic opportunities for tackling the disease.
Hydrogen-bonding patterns in 2,2-bis(4-methylphenyl)hexafluoropropane pyridinium and ethylenediammonium salt crystals. Corrigendum
Authors: Sugiyama Haruki
Published: October 2020

In the paper by Sugiyama [Acta Cryst. (2020), E76, 742–746], there is an error in the chemical names of the title compounds.
Fifteen 4-(2-methoxyphenyl)piperazin-1-ium salts containing organic anions: supramolecular assembly in zero, one, two and three dimensions
Authors: Harish Chinthal Chayanna , Kavitha Channappa N. , Yathirajan Hemmige S. , Foro Sabine , Rathore Ravindranath S. , Glidewell Christopher
Published: October 2020

Fifteen 4-(2-methoxyphenyl)piperazin-1-ium salts containing organic anions have been prepared and structurally characterized. In the isostructural 4-chlorobenzoate and 4-bromobenzoate salts, C11H17N2O+·C7H4ClO2
− (I) and C11H17N2O+·C7H4BrO2
− (II), and the 4-iodobenzoate salt C11H17N2O+·C7H4IO2
− (III), the ions are linked by N—H...O hydrogen bonds, forming centrosymmetric R
4
4(12) four-ion aggregates; a similar aggregate is formed in the 2-chlorobenzoate salt (V), isomeric with (I). In the 2-fluorobenzoate salt C11H17N2O+·C7H4FO2
− (IV), and the isomorphous pair of salts, the 2-bromobenzoate (VI), isomeric with (II) and 2-iodobenzoate (VII), isomeric with (III), N—H...O and C—H...π(arene) interactions link the components into three-dimensional arrays. Four-ion R
4
4(12) aggregates are also found in the 2-methylbenzoate, 4-aminobenzoate and 4-nitrobenzoate salts, C11H17N2O+·C8H7O2
− (VIII), C11H17N2O+·C7H6NO2
− (IX) and C11H17N2O+·C7H4NO4
− (X), but those in (IX) are linked into complex sheets by an additional N—H...O hydrogen bond. In the 3,5-dinitrobenzoate salt, C11H17N2O+·C7H3N2O6
−·2H2O (XI), N—H...O and O—H...O hydrogen bonds link the components into a complex ribbon structure. In the picrate salt, C11H17N2O+·C6H2N3O7
− (XII), the four-ion aggregates are linked into chains of rings by C—H...O hydrogen bonds. In the hydrogen maleate salt, C11H17N2O+·C4H3O4
− (XIII), two- and three-centre hydrogen bonds link the ions into a ribbon structure while both anions contain very short but asymmetric O—H...O hydrogen bonds, having O...O distances of 2.4447 (16) and 2.4707 (17) Å. O—H...O Hydrogen bonds link the anions in the hydrogen fumarate salt (XIV), isomeric with (XIII), into chains that are linked into sheets via N—H...O hydrogen bonds. In the hydrogen (2R,3R)-tartrate salt, C11H17N2O+·C4H5O6
−·1.698H2O (XV), the anions are linked into sheets by O—H...O hydrogen bonds. Comparisons are made with the structures of some related compounds.