bluuebunny/crossref_metadata_2025 huggingface dataset:
Translational profiling of mouse dopaminoceptive neurons reveals a role of PGE2 in dorsal striatum
Authors: Montalban Enrica , Giralt Albert , Taing Lieng , Nakamura Yuki , Martin Claire , de Pins Benoit , Pelosi Assunta , Goutebroze Laurence , Castell Laia , Wang Wei , Neiburga Kathrina Daila , Vestito Letizia , Nairn Angus C. , Valjent Emmanuel , Hervé Denis , Heintz Nathaniel , Le Novère Nicolas Gambardella , Greengard Paul , Roussarie Jean-Pierre , Girault Jean-Antoine
Published: September 2020

Forebrain dopaminoceptive neurons play a key role in movement, action selection, motivation, and working memory. Their activity is dysregulated in addiction, Parkinson’s disease and other conditions. To characterize the diverse dopamine target neuronal populations, we compare translating mRNAs in neurons of dorsal striatum and nucleus accumbens expressing D1 or D2 dopamine receptor and prefrontal cortex expressing D1 receptor. We identify D1/D2 and striatal dorso-ventral differences in the translational and splicing landscapes, which establish the characteristics of dopaminoceptive neurons. Expression differences and network analyses identify novel transcription factors with presumptive roles in these differences. Prostaglandin E2 appears as a candidate upstream regulator in the dorsal striatum, a hypothesis supported by converging functional evidence indicating its role in enhancing D2 dopamine receptor action. Our study provides powerful resources for characterizing dopamine target neurons, new information about striatal gene expression patterns, and reveals the unforeseen role of prostaglandin E2 in the dorsal striatum.
Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations
Authors: Rees Elliott , Creeth Hugo D. J. , Hwu Hai-Gwo , Chen Wei J. , Tsuang Ming , Glatt Stephen J. , Rey Romain , Kirov George , Walters James T. R. , Holmans Peter , Owen Michael J. , O’Donovan Michael C.
Published: September 2020

Genes enriched for rare disruptive coding variants in schizophrenia overlap those in which disruptive mutations are associated with neurodevelopmental disorders (NDDs), particularly autism spectrum disorders and intellectual disability. However, it is unclear whether this implicates the same specific variants, or even variants with the same functional effects on shared risk genes. Here, we show thatde novomutations in schizophrenia are generally of the same functional category as those that confer risk for NDDs, and that the specificde novomutations in NDDs are enriched in schizophrenia. These findings indicate that, in part, NDDs and schizophrenia have shared molecular aetiology, and therefore likely overlapping pathophysiology. We also observe pleiotropic effects for variants known to be pathogenic for several syndromic developmental disorders, suggesting that schizophrenia should be included among the phenotypes associated with these mutations. Collectively, our findings support the hypothesis that at least some forms of schizophrenia lie within a continuum of neurodevelopmental disorders.
A feedback loop between the androgen receptor and 6-phosphogluoconate dehydrogenase (6PGD) drives prostate cancer growth
Authors: Gillis Joanna L. , Hinneh Josephine A. , Ryan Natalie , Irani Swati , Moldovan Max , Shrestha Raj , Quek Lake Ee , Hoy Andrew J. , Holst Jeff , Centenera Margaret M. , Mills Ian G. , Lynn David J. , Selth Luke A. , Butler Lisa M.
Published: September 2020

Alterations to androgen receptor (AR) signalling and cellular metabolism are hallmarks of prostate cancer. This study uncovers a novel link between AR and the pentose phosphate pathway (PPP) through 6-phosphogluoconate dehydrogenase (6PGD), an androgen-regulated gene that is upregulated in prostate cancer. Knockdown of 6PGD impairs growth and elicits death of prostate cancer cells, at least in part due to oxidative stress. Targeting 6PGD using 2 specific inhibitors, physcion and S3, was efficacious in multiple models of prostate cancer, including aggressive castration-resistant models. Importantly, S3 also suppressed proliferation of clinical patient-derived explants (PDEs). Mechanistically, 6PGD decreased expression and activity of AR in cell lines and PDEs, revealing a novel positive feedback loop between these factors. The enhanced efficacy of co-targeting AR and 6PGD further supported the biological relevance of this feedback. This work provides insight into the dysregulated metabolism of prostate cancer and supports investigation of co-targeting AR and the PPP.
A connectome-based prediction model of long-term memory
Authors: Lin Qi , Yoo Kwangsun , Shen Xilin , Constable R Todd , Chun Marvin M
Published: September 2020

Although many studies have investigated the neural basis of intra-individual fluctuations in long-term memory (LTM), few have explored the differences across individuals. Here, we characterize a whole-brain functional connectivity (FC) network based on fMRI data in an n-back task that robustly predicts individual differences in LTM. Critically, although FC during the n-back task also predicted working memory (WM) performance and the two networks had some shared components, they are also largely distinct from each other: the LTM model performance remained robust when we controlled for WM and vice versa. Furthermore, regions important for LTM such as the medial temporal lobe did contribute, but only partially, to predicting LTM. These results demonstrate that individual differences in LTM are dependent on the configuration of a whole-brain functional network including but not limited to regions traditionally associated with LTM during encoding and that such a network is separable from what supports WM.
Atypical Neocortical Development in theCited2Conditional Knockout Leads to Behavioral Deficits Associated with Neurodevelopmental Disorders
Authors: Wagner Nikolaus , MacDonald Jessica L.
Published: September 2020

The mammalian neocortex develops from a single layer of neuroepithelial cells to form a six-layer heterogeneous mosaic of differentiated neurons and glial cells. This process requires a complex choreography of temporally and spatially restricted transcription factors and epigenetic regulators. Even subtle disruptions in this regulation can alter the way the neocortex forms and functions, leading to a neurodevelopmental disorder. One epigenetic regulator that is essential for the precise development of the neocortex is CITED2 (CBP/p300InteractingTransactivator withED-rich termini).Cited2is highly expressed by intermediate progenitor cells in the subventricular zone during the generation of the superficial layers of the neocortex. A forebrain-specific conditional knockout ofCited2(cKO) exhibits reduced proliferation of intermediate progenitor cells embryonically, leading to reduced thickness of the superficial layers and a specific reduction in the somatosensory neocortical length postnatally. Further, theCited2cKO displays decreased corpus callosum volume and dysregulation of precise neuronal connectivity within the somatosensory cortex. Here, we explore the behavioral consequences resulting from this aberrant neocortical development. We demonstrate thatCited2cKO mice display decreased maternal separation-induced ultrasonic vocalizations as neonates, and an increase in the repetitive behavior of rearing and lack of habituation following repeated acoustic startle as adults. They do not display alterations in anxiety-like behavior, overall locomotor activity or social interactions. Together with the morphological, molecular, and connectivity disruptions, these results identify theCited2cKO neocortex as an ideal system to study mechanisms underlying neurodevelopmental and neuroanatomical disruptions with relevance to human neurodevelopmental disorders.
Development of a copper-graphene nanocomposite based transparent coating with antiviral activity against influenza virus
Authors: Das Jana Indrani , Kumbhakar Partha , Banerjee Saptarshi , Gowda Chinmayee Chowde , Kedia Nandita , Kuila Saikat Kumar , Banerjee Sushanta , Das Narayan Chandra , Das Amit Kumar , Manna Indranil , Tiwary Chandra Sekhar , Mondal Arindam
Published: September 2020

Respiratory infections by RNA viruses are one of the major burdens upon global health and economy. Viruses like influenza or coronaviruses can be transmitted through respiratory droplets or contaminated surfaces. An effective antiviral coating can decrease the viability of the virus particles in the outside environment significantly, hence reducing their transmission rate. In this work, we have screened a series of nanoparticles and their composites for antiviral activity using Nano Luciferase based highly sensitive influenza A reporter virus. Using this screening system, we have identified copper-graphene (Cu-Gr) nanocomposite shows strong antiviral activity. Extensive material and biological characterization of the nanocomposite suggested a unique metal oxide embedded graphene sheet architecture that can inactivate the virion particles only within 30 minutes of pre-incubation and subsequently interferes with the entry of these virion particles into the host cell. This ultimately results in reduced viral gene expression, replication and production of progeny virus particles, slowing down the overall pace of progression of infection. Using PVA as a capping agent, we have been able to generate a Cu-Gr nanocomposite based highly transparent coating that retains its original antiviral activity in the solid form.
The sheep brain: an interesting translational model for functional MRI studies?
Authors: Just Nathalie , Adriaensen Hans , Chevillard Pierre-Marie , Batailler Martine , Dubois Jean-Philippe , Migaud Martine
Published: September 2020

Biomedical investigations in clinically relevant animal models is of crucial interest for faster and appropriate transfer to human. The ovine model has already demonstrated its potential compared to rodents and non-human primates (NHP) in various studies: sheep possess a gyrencephalic brain, captivity is not an issue and can undergo magnetic resonance imaging (MRI) in routine clinical scanners (1.5T, 3T) under identical conditions using similar techniques to humans. To date, the effects of anesthesia have been poorly explored and only few functional MRI (fMRI) studies were conducted in sheep. Here, Blood Oxygen Level dependent fMRI and perfusion MRI were conducted in lambs and adult ewes at 3 T. Robust but weak BOLD responses to visual stimulation were found in the lateral geniculate nucleus (LGN) up to 3% isoflurane anaesthesia. BOLD responses were weaker in adult sheep than in lambs while relative cerebral blood volumes (rCBV) and relative cerebral blood flows (rCBF) were significantly higher in lambs than in adult sheep for both gray and white matter in accordance with previous findings in the human. Assessment of functional responses in healthy individuals under adequate physiological conditions is essential for robust translational studies.
Cellular aging in vitro recapitulates multi-tissue epigenetic aging in vivo
Authors: Minteer Christopher , Morselli Marco , Meer Margarita , Cao Jian , Higgins-Chen Albert , Lang Sabine , Pellegrini Matteo , Yan Qin , Levine Morgan
Published: September 2020

ii.

Aging is known to elicit dramatic changes to DNA methylation (DNAm), although the causes and consequences of such alterations are not clear and require further exploration. Our ability to experimentally uncover mechanisms of epigenetic aging will be greatly enhanced by our ability to study and manipulate these changes usingin vitromodels. However, it remains unclear whether the changes elicited by cells in culture can serve as a model of what is observed in aging tissuesin vivo. To test this, we serially passaged mouse embryonic fibroblasts (MEFs) and assessed changes in DNAm at each time-point via RRBS. By developing a measure that tracked cellular agingin vitro, we tested whether it tracked physiological aging in various mouse tissues and whether anti-aging interventions modulate this measure. Our measure, termed DNAmCULTURE, was shown to strongly increase with age when examined in multiple tissues (liver, lung, kidney, blood, and adipose). As a control, we confirmed that the measure was not a marker of cellular senescence, suggesting that it reflects a distinct yet progressive cellular aging phenomena that can be inducedin vitro. Furthermore, we demonstrated slower epigenetic aging in animals undergoing caloric restriction and a resetting of our measure in lung and kidney fibroblasts when re-programmed to iPSCs. Enrichment and clustering analysis implicated SUZ12, EED and Polycomb group (PcG) factors as potentially important chromatin regulators in translational culture aging phenotypes. Overall, this study supports the concept that physiologically relevant aging changes can be inducedin vitroand moving forward, used to uncover mechanistic insights into epigenetic aging.
RiboTag-Seq Reveals the Activation of the Unfolded Protein Response in Striatal Microglia Induced by Ethanol Withdrawal
Authors: Dufour Brett D. , Coffey Kevin R. , Lesiak Atom J. , Garden Gwenn A. , Neumaier John F.
Published: September 2020

Repeated cycles of alcohol intoxication and withdrawal both induce profound changes in gene expression that can contribute to the physiological and behavioral consequences of ethanol. Since neuroinflammation is an important consequence of these changes, we used a novel strategy to investigate the impact of repeated cycles of chronic intermittent ethanol vapor and withdrawal on the RNAs actively undergoing translation in striatal microglia. RiboTag was selectively expressed in the microglia of transgenic mice and was used to immunopurify the RNA “translatome” from striatal microglia, yielding a snapshot of RNA translation during alcohol intoxication and after 8 hours of withdrawal. We obtained highly enriched microglial RNAs and analyzed these in individual animals by deep sequencing. We found a dramatic shift in gene expression during acute intoxication compared to air-exposed controls, with increases in genes and pathways associated with cytokine signaling, indicating increased neuroinflammation and microglial activation. After 8 hours of ethanol withdrawal, many inflammatory pathways remained upregulated but phagocytotic and proapoptotic pathways were increased. Using an unbiased bioinformatic method, weighted gene coexpression network analysis, multiple differentially expressed gene modules were identified. One in particular was differentially expressed in ethanol intoxicated vs. withdrawing animals, and there was a strong correlation between the centrality of the genes to this gene network and their individual statistical significance in differential expression. The unfolded protein response was over-represented in this network after withdrawal. The induction of this pathway in microglia is important since this cellular stress response can either lead towards restoration of normal function or apoptosis.
Leveraging complex interactions between signaling pathways involved in liver development to robustly improve the maturity and yield of pluripotent stem cell-derived hepatocytes
Authors: Raggi Claudia , M’Callum Marie-Agnès , Pham Quang Toan , Gaub Perrine , Selleri Silvia , Baratang Nissan , Mangahas Chenicka Lyn , Cagnone Gaël , Reversade Bruno , Joyal Jean-Sébastien , Paganelli Massimiliano
Published: September 2020

Pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLC) have shown great potential as an alternative to primary human hepatocytes (PHH) forin vitromodeling. Several differentiation protocols have been described to direct PSC towards the hepatic fate, although the resulting HLC have shown more a fetal than adult phenotype. Here, by leveraging recent knowledge of the signaling pathways involved in liver development, we describe a robust, scalable protocol that allows to consistently generate high-quality HLC from both ESC and iPSC. Such HLC are comparable to adult PHH in terms of key mature liver functions and proved suitable to assess drug hepatotoxicity, as a proof of concept of their potential as a physiologically representative alternative forin vitromodeling.
SUMOylation- and GAR1-dependent regulation of dyskerin nuclear and subnuclear localization
Authors: MacNeil D.E. , Lambert-Lanteigne P. , Qin J. , McManus F. , Bonneil E. , Thibault P. , Autexier C.
Published: September 2020

Dyskerin, a telomerase-associated protein and H/ACA ribonucleoprotein complex component plays an essential role in human telomerase assembly and activity. The nuclear and subnuclear compartmentalization of dyskerin and the H/ACA complex is an important though incompletely understood aspect of H/ACA ribonucleoprotein function. The posttranslational modification, SUMOylation, targets a wide variety of proteins, including numerous RNA-binding proteins, and most identified targets reported to date localize to the nucleus. Four SUMOylation sites were previously identified in the C-terminal Nuclear/Nucleolar Localization Signal (N/NoLS) of dyskerin, each located within one of two lysine-rich clusters. We found that a cytoplasmic localized C-terminal truncation variant of dyskerin lacking most of the C-terminal N/NoLS and both lysine-rich clusters represents an under-SUMOylated variant of dyskerin compared to wildtype dyskerin. We demonstrate that mimicking constitutive SUMOylation of dyskerin using a SUMO3-fusion construct can drive nuclear accumulation of this variant, and that the SUMO site K467 in this N/NoLS is particularly important for the subnuclear localization of dyskerin to the nucleolus in a mature H/ACA complex assembly- and SUMO-dependent manner. We also characterize a novel SUMO-interacting motif in the mature H/ACA complex component GAR1 that mediates the interaction between dyskerin and GAR1. Mislocalization of dyskerin, either in the cytoplasm or excluded from the nucleolus, disrupts dyskerin function and leads to reduced interaction of dyskerin with the telomerase RNA. These data indicate a role for dyskerin C-terminal N/NoLS SUMOylation in regulating the nuclear and subnuclear localization of dyskerin, which is essential for dyskerin function as both a telomerase-associated protein and as an H/ACA ribonucleoprotein involved in rRNA and snRNA biogenesis.
The Combination of Morphology and Surface Chemistry Defines the Biological Identity of Nanocarriers in Human Blood
Authors: Karabin Nicholas B. , Vincent Michael P. , Allen Sean D. , Bobbala Sharan , Frey Molly A. , Yi Sijia , Yang Yufan , Scott Evan A.
Published: September 2020

Following intravenous administration, an adsorbed corona of blood proteins immediately forms on the surfaces of nanocarriers to confer a distinct biological identity that dictates interactions with the immune system. While the nanocarrier surface chemistry has long been the focus of protein corona formation, the influence of the nanocarrier structure has remained unclear despite well-documented influences on biodistribution, clearance and inflammation. Here, we present design rules for the combined engineering of both nanocarrier structure and surface chemistry derived from a comprehensive proteomic analysis of protein corona formation in human blood. A library of nine soft PEGylated nanocarriers that differ in their combination of morphology (spheres, vesicles, and cylinders) and surface chemistry (methoxy, hydroxyl, and phosphate) were synthesized to represent properties of commonly employed drug delivery vehicles. Using label-free proteomics and high-throughput techniques, we examined the relationship between physicochemical properties and the resulting nanocarrier biological identity, including dynamic changes in protein corona composition, differential immunostimulation and uptake by relevant immune cell populations. In human blood, non-polar spherical micelles developed a similar biological identity to polar vesicles, whereas the identities of polar spheres and cylinders resembled that of non-polar vesicles. The formed protein coronas were compositionally dynamic and morphology-dependent, and these time-dependent fingerprints altered nanocarrier complement activation as well as their uptake by human monocytes, macrophages, and dendritic cells. This comprehensive analysis provides mechanistic insights into rational design choices that impact nanocarrier fate in human blood.

One Sentence Summary

We demonstrate that not only the surface chemistry, but the combined chemical and structural properties of soft drug delivery vehicles impact the composition of blood proteins that adsorb to their surfaces, and these differences specify their interactions with and modulation of human immune cells.
Genome-wide SNP detection in Darjeeling tea: unravelling genetic structure, functional impact and trait associations
Authors: Hazra Anjan , Kumar Rakesh , Sengupta Chandan , Das Sauren
Published: September 2020

Genotyping by sequencing and identification of functionally relevant nucleotide variations in crop accessions are the key steps to unravel genetic control of desirable traits. In the scope of present work, elite cultivars of Darjeeling tea were undergone SNP genotyping by double-digest restriction site associated DNA sequencing method. This study reports a set of 54,206 high-quality SNP markers discovered from ∼10.4 GB sequence data, encompassing 15 chromosomes of reference tea genome. Genetic relatedness among the accessions conforms to the analyses of Bayesian clustering, UPGMA, and PCoA methods. High percent of heterozygous loci in the majority of the cultivars reflect their ‘hybrid’ ancestry as reported earlier. Genomic positions of the discovered SNPs and their putative effect on annotated genes designated a thoughtful understanding of their functional aspects in tea system biology. A group of 95 genes was identified to be affected by high impact variants, most of them are involved in signal transduction, biosynthesis of secondary metabolite, transcriptional and translational regulation. Genome-wide association analyses of 21 agronomic and biochemical phenotypes resulted in trait-linked polymorphic loci with strong confidence (p< 0.05 and 0.001). The selection of significant marker-trait associations with the Bonferroni correction threshold retained a set of 57 SNPs distributed across 14 chromosomes to be linked with eight phenotypic traits. High impact and trait-associated nucleotide polymorphisms perceived in this study can be exploited in worldwide germplasm of contrasting origin to depict their heritability and to unlock their potentiality in marker-assisted breeding.
Evolution and regulation of microbial secondary metabolism
Authors: Santamaria Guillem , Liao Chen , Wang Zhe , Rhee Kyu , Pinto Francisco , Yan Jinyuan , Xavier Joao B.
Published: September 2020

Microbes have disproportionate impacts on the macroscopic world. This is in part due to their ability to grow to large groups and cooperatively secrete massive amounts of secondary metabolites that impact their environment. Yet, the conditions enabling secondary metabolism without compromising primary needs remain unclear. Here we investigated the biosynthesis of rhamnolipids, a secondary metabolite thatPseudomonas aeruginosamakes to decrease the surface tension of surrounding liquid. Using a combination of genomics, metabolomics, transcriptomics, and mathematical modeling we show that biosynthesis of rhamnolipids from glycerol varies inconsistently across the phylogenetic tree; instead, non-producer lineages are also those worse at reducing the oxidative stress of primary glycerol metabolism. The link to oxidative stress explains the inconsistent distribution across theP. aeruginosatree, adding a new layer to the regulation of rhamnolipids—a microbial secondary metabolite important for fitness in natural and clinical settings.

Significance

The bacteriumPseudomonas aeruginosais a major source of hospital-acquired infections. This pathogen’s knack for virulence relies on its ability to multiply and secrete massive amounts of substances that overwhelm microbial competitors and weaken host defenses. It remains unclear how the bacteria conciliate their need to grow and multiply—a need at the individual-level— with their ability to secrete products—a need of the population. Here we combined genomics, metabolomics and mathematical modeling to study the biosynthesis of rhamnolipids, a surfactant thatP. aeruginosamakes to reduce the surface tension of surrounding liquids. Our study reveals a new link between oxidative stress and rhamnolipid synthesis, which helps explain how this important bacterial product has evolved and how it persists in many lineages of pathogens.
Identification of a novel cobamide remodeling enzyme in the beneficial human gut bacteriumAkkermansia muciniphila
Authors: Mok Kenny C. , Sokolovskaya Olga M. , Nicolas Alexa M. , Hallberg Zachary F. , Deutschbauer Adam , Carlson Hans K. , Taga Michiko E.
Published: September 2020

The beneficial human gut bacteriumAkkermansia muciniphilaprovides metabolites to other members of the gut microbiota by breaking down host mucin, but most of its other metabolic functions have not been investigated.A. muciniphilais known to use cobamides, the vitamin B12family of cofactors with structural diversity in the lower ligand, though the specific cobamides it can use have not been examined. We found that growth ofA. muciniphilastrain MucTwas nearly identical with each of seven cobamides tested, in contrast to nearly all bacteria that have been studied. Unexpectedly, this promiscuity is due to cobamide remodeling – the removal and replacement of the lower ligand – despite the absence of the canonical remodeling enzyme CbiZ inA. muciniphila. We identified a novel enzyme, CbiR, that is capable of initiating the remodeling process by hydrolyzing the phosphoribosyl bond in the nucleotide loop of cobamides. CbiR does not share homology with other cobamide remodeling enzymes or B12-binding domains, and instead is a member of the AP endonuclease 2 enzyme superfamily. We speculate that CbiR enables bacteria to repurpose cobamides they otherwise cannot use in order to grow under a cobamide-requiring condition; this function was confirmed by heterologous expression ofcbiRinE. coli. Homologs of CbiR are found in over 200 microbial taxa across 22 phyla, suggesting that many bacteria may use CbiR to gain access to the diverse cobamides present in their environment.

Importance

Cobamides, the vitamin B12family of cobalt-containing cofactors, are required for metabolism in all domains of life, including most bacteria. Cobamides have structural variability in the lower ligand, and selectivity for particular cobamides has been observed in most organisms studied to date. Here, we discover that the beneficial human gut bacteriumAkkermansia muciniphilacan use a diverse range of cobamides due to its ability to change the cobamide structure via “cobamide remodeling”. We identify and characterize the novel enzyme CbiR that is necessary for initiating the cobamide remodeling process. The discovery of this enzyme has implications not only for understanding the ecological role ofA. muciniphilain the gut, but for other bacteria that carry this enzyme as well.
A balance between matrix deformation and the coordination of turning events governs directed neutrophil migration in 3-D matrices
Authors: François Joshua , Kandasamy Adithan , Yeh Yi-Ting , Ayala Cindy , Meili Ruedi , Chien Shu , Lasheras Juan C. , del Álamo Juan C.
Published: September 2020

Three-dimensional (3-D) neutrophil migration is essential for immune surveillance and inflammatory responses. During 3-D migration, especially through extravascular spaces, neutrophils rely on frontal protrusions and rear contractions to squeeze and maneuver through extracellular matrices containing narrow pores. However, the role of matrix density and the cells’ ability to probe and remodel matrix pores during 3-D chemotaxis are far from being understood. We investigated these processes by tracking the trajectories of over 20,000 neutrophils in a 3-D migration device containing collagen matrices of varying concentrations and analyzing the shape of these trajectories at multiple scales. Additionally, we quantified the transient 3-D matrix deformations caused by the migrating cells. The mean pore size of our reconstituted collagen matrices decreased when the collagen concentration ([col]) was increased. In low-[col] matrices, neutrophils exerted large transient deformations and migrated in relatively straight trajectories. In contrast, they were not able to appreciably deform high- [col] matrices and adapted to this inability by turning more often to circumvent these narrow matrix pores. While this adaptation resulted in slower migration, the cells were able to balance the more frequent turning with the long-range directional bias necessary for chemotaxis. Based on our statistical analysis of cell trajectories, we postulate that neutrophils achieve this balance by using matrix obstacles as pivoting points to steer their motion towards the chemoattractant. Inhibiting myosin-II contractility or Arp2/3-mediated pseudopod protrusions not only compromised the cells’ ability to deform the matrix, but also made them switch to increased turning in more restrictive matrices when compared to untreated control cells. Both myosin-II contractility and Arp2/3-mediated branched polymerization of actin played a role in fast migration, but Arp2/3 was also crucial for neutrophils when coordinating the orientations of successive turns to prevent veering away from the chemotactic path. These results may contribute to an improved understanding of the mechanisms employed by migrating neutrophils in confined 3-D environments, as well as the molecular and environmental regulators for maintaining persistent motion.
Optimization of negative stage bias potential for faster imaging in large-scale electron microscopy
Authors: Lane Ryan , Vos Yoram , Wolters Anouk H. G. , van Kessel Luc , Giepmans Ben N.G. , Hoogenboom Jacob P.
Published: September 2020

Large-scale electron microscopy (EM) allows analysis of both tissues and macromolecules in a semi-automated manner, but acquisition rate forms a bottleneck. We reasoned that a negative bias potential may be used to enhance signal collection, allowing shorter dwell times and thus increasing imaging speed. Negative bias potential has previously been used to tune penetration depth in block-face imaging. However, optimization of negative bias potential for application in thin section imaging will be needed prior to routine use and application in large-scale EM. Here, we present negative bias potential optimized through a combination of simulations and empirical measurements. We find that the use of a negative bias potential generally results in improvement of image quality and signal-to-noise ratio (SNR). The extent of these improvements depends on the presence and strength of a magnetic immersion field. Maintaining other imaging conditions and aiming for the same image quality and SNR, the use of a negative stage bias can allow for a 20-fold decrease in dwell time, thus reducing the time for a week long acquisition to less than 8 hours. We further show that negative bias potential can be applied in an integrated correlative light electron microscopy (CLEM) application, allowing fast acquisition of a high precision overlaid LM-EM dataset. Application of negative stage bias potential will thus help to solve the current bottleneck of image acquisition of large fields of view at high resolution in large-scale microscopy.
Massive expansion of human gut bacteriophage diversity
Authors: Camarillo-Guerrero Luis F. , Almeida Alexandre , Rangel-Pineros Guillermo , Finn Robert D. , Lawley Trevor D.
Published: September 2020

Bacteriophages drive evolutionary change in bacterial communities by creating gene flow networks that fuel ecological adaptions. However, the extent of viral diversity and prevalence in the human gut remains largely unknown. Here, we introduce the Gut Phage Database (GPD), a collection of ∼142,000 non-redundant viral genomes (>10 kb) obtained by mining a dataset of 28,060 globally distributed human gut metagenomes and 2,898 reference genomes of cultured gut bacteria. Host assignment revealed that viral diversity is highest in the Firmicutes phyla and that ∼36% of viral clusters (VCs) are not restricted to a single species, creating gene flow networks across phylogenetically distinct bacterial species. Epidemiological analysis uncovered 280 globally distributed VCs found in at least 5 continents and a highly prevalent novel phage clade with features reminiscent of p-crAssphage. This high-quality, large-scale catalogue of phage genomes will improve future virome studies and enable ecological and evolutionary analysis of human gut bacteriophages.
Testing methods of linguistic homeland detection using synthetic data
Authors: Wichmann Søren , Rama Taraka
Published: September 2020

Two families of quantitative methods have been used to infer geographical homelands of language families: Bayesian phylogeography and the ‘diversity method’. Bayesian methods model how populations may have moved using a phylogenetic tree as a backbone, while the diversity method assumes that the geographical area where linguistic diversity is highest likely corresponds to the homeland. No systematic tests of the performances of the different methods in a linguistic context have so far been published. Here we carry out performance testing by simulating language families, including branching structures and word lists, along with speaker populations moving in space. We test six different methods: two versions of BayesTraits; the relaxed random walk model of BEAST 2; our own RevBayes implementations of a fixed rates and a variable rates random walk model; and the diversity method. As a result of the tests we propose a hierarchy of performance of the different methods. Factors such as geographical idiosyncrasies, incomplete sampling, tree imbalance, and small family sizes all have a negative impact on performance, but mostly across the board, the performance hierarchy generally being impervious to such factors.
Phylogenomic relationships and historical biogeography in the South American vegetable ivory palms (Phytelepheae)
Authors: Escobar Sebastián , Helmstetter Andrew J. , Montúfar Rommel , Couvreur Thomas L. P. , Balslev Henrik
Published: September 2020

The vegetable ivory palms (Phytelepheae) form a small group of Neotropical palms whose phylogenetic relationships are not fully understood. Three genera and eight species are currently recognized; however, it has been suggested that Phytelephas macrocarpa could include the species Phytelephas seemannii and Phytelephas schottii because of supposed phylogenetic relatedness and similar morphology. We inferred their phylogenetic relationships and divergence time estimates using the 32 most clock-like loci of a custom palm bait-kit formed by 176 genes and four fossils for time calibration. We additionally explored the historical biogeography of the tribe under the recovered phylogenetic relationships. Our fossil-dated tree showed the eight species previously recognized, and that P. macrocarpa is not closely related to P. seemanii and P. schottii, which, as a consequence, should not be included in P. macrocarpa. The ancestor of the vegetable ivory palms was widely-distributed in the Chocó, the inter-Andean valley of the Magdalena River, and the Amazonia during the Miocene at 19.25 Ma. Early diversification in Phytelephas at 5.27 Ma can be attributed to trans-Andean vicariance between the Chocó/Magdalena and the Amazonia. Our results support the role of Andean uplift in the early diversification of Phytelephas under new phylogenetic relationships inferred from genomic data.
Genomic analyses of two Italian oyster mushroomPleurotus pulmonariusstrains
Authors: de Ulzurrun Guillermo Vidal-Diez , Lee Yi-Yun , Stajich Jason E. , Schwarz Erich M. , Hsueh Yen-Ping
Published: September 2020

Pleurotusmushrooms are among the most cultivated fungi in the world and are highly valuable for food, medicine and biotechnology industries. Furthermore,Pleurotusspecies are carnivorous fungi; they can rapidly paralyze and kill nematodes when nutrient-deprived. The predator-prey interactions betweenPleurotusand nematodes are still widely unexplored. Moreover, the molecular mechanisms and the genes involved in the carnivorous behavior ofPleurotusmushrooms remain a mystery. We are attempting to understand the interactions betweenPleurotusmushrooms and their nematode prey through genetic and genomic analyses. Two single spores (ss2 and ss5) isolated from a fruiting body ofPleurotus pulmonariusexhibited significant differences in growth and toxicity against nematodes. Thus, using PacBio long reads, we assembled and annotated two high-quality genomes for these two isolates ofPleurotus pulmonarius. Each of these assemblies contains 23 scaffolds, including 6 (ss2) and 8 (ss5) telomere-to-telomere scaffolds, and they are among the most complete assembled genomes of thePleurotusspecies. Comparative analyses identified the genomic differences between the twoP. pulmonariusstrains. In sum, this work provides a genomic resource that will be invaluable for better understanding the Italian oyster mushroomP. pulmonarius.
Bayesian Connective Field Modeling: a Markov Chain Monte Carlo approach
Authors: Invernizzi Azzurra , Haak Koen V. , Carvalho Joana C. , Renken Remco J. , Cornelissen Frans W.
Published: September 2020

The majority of neurons in the human brain process signals from neurons elsewhere in the brain. Connective Field (CF) modeling is a biologically-grounded method to describe this essential aspect of the brain’s circuitry. It allows characterizing the response of a population of neurons in terms of the activity in another part of the brain. CF modeling translates the concept of the receptive field (RF) into the domain of connectivity by assessing the spatial dependency between signals in distinct cortical visual field areas. Standard CF model estimation has some intrinsic limitations in that it cannot estimate the uncertainty associated with each of its parameters. Obtaining the uncertainty will allow identification of model biases, e.g. related to an over- or under-fitting or a co-dependence of parameters, thereby improving the CF prediction. To enable this, here we present a Bayesian framework for the CF model. Using a Markov Chain Monte Carlo (MCMC) approach, we estimate the underlying posterior distribution of the CF parameters and consequently, quantify the uncertainty associated with each estimate. We applied the method and its new Bayesian features to characterize the cortical circuitry of the early human visual cortex of 12 healthy participants that were assessed using 3T fMRI. In addition, we show how the MCMC approach enables the use of effect size (beta) as a data-driven parameter to retain relevant voxels for further analysis. Finally, we demonstrate how our new method can be used to compare different CF models. Our results show that single Gaussian models are favoured over differences of Gaussians (i.e. center-surround) models, suggesting that the cortico-cortical connections of the early visual system do not possess center-surround organisation. We conclude that our new Bayesian CF framework provides a comprehensive tool to improve our fundamental understanding of the human cortical circuitry in health and disease.

Highlights

□ We present and validate a Bayesian CF framework based on a MCMC approach.

□ The MCMC CF approach quantifies the model uncertainty associated with each CF parameter.

□ We show how to use effect sizebetaas a data-driven threshold to retain relevant voxels.

□ The cortical connective fields of the human early visual system are best described by a single, circular symmetric, Gaussian.
The Nubeam reference-free approach to analyze metagenomic sequencing reads
Authors: Dai Hang , Guan Yongtao
Published: September 2020

We present Nubeam (nucleotide be amatrix) as a novel reference-free approach to analyze short sequencing reads. Nubeam represents nucleotides by matrices, transforms a read into a product of matrices, and assigns numbers to reads based on the product matrix. Nubeam capitalizes on the noncommutative property of matrix multiplication, such that different reads are assigned different numbers and similar reads similar numbers. A sample, which is a collection of reads, becomes a collection of numbers that form an empirical distribution. We demonstrate that the genetic difference between samples can be quantified by the distance between empirical distributions. Nubeam includes the k-mer method as a special case, but unlike the k-mer method, it is convenient for Nubeam to account for GC bias and nucleotide quality. As a reference-free approach, Nubeam avoids reference bias and mapping bias, and can work with organisms without reference genomes. Thus, Nubeam is ideal to analyze data sets from metagenomics whole genome shotgun (WGS) sequencing, where the amount of unmapped reads is substantial. When applied to a WGS sequencing data set to quantify distances between metagenomics samples from various human body habitats, Nubeam recapitulates findings made by mapping-based methods and sheds light on contributions of unmapped reads. Nubeam is also useful in analyzing 16S rRNA sequencing data, which is a more prevalent type of data set in metagenomics studies. In our analysis, Nubeam recapitulated the findings that natural microbiota in mouse gut are resilient under challenges, and Nubeam detected differences in vaginal microbiota between cases of polycystic ovary syndrome and healthy controls.
The labor share and income inequality: some empirical evidence for the period 1990-2015
Authors: Erauskin Iñaki
Published: September 2020

Purpose

The purpose of this paper is to analyze empirically the relationship between the labor share and income inequality, as measured by the Gini coefficient and by the income shares for different quintiles, during the period 1990–2015 for 62 developed and developing countries.

Design/methodology/approach

This study uses panel data techniques to analyze empirically the relationship between the labor share and income inequality.

Findings

This paper finds that a lower labor share is associated with a higher Gini coefficient. A lower labor share is found to be strongly associated with a smaller income share for the lowest two quintiles and larger income share for the highest quintile and weakly associated with a smaller income share for the third and fourth quintiles. Moreover, this paper finds that the lower the quintile, the stronger the impact of the labor share on the income share of the quintile.

Social implications

Policymakers should take into account the evolution of the labor share. Public policies that improve labor market outcomes, such as those aimed to promote participation in the labor market and strengthen the human capital of low-income groups, seem necessary to prevent the rise in economic inequalities. Moreover, as the digital transformation of society progresses, policies to promote skill deepening may have an important role in reversing excessive inequalities.

Originality/value

How changes in the labor share are associated with changes in the Gini coefficient, and how this is driven by income shares for different quintiles, for a broad range of countries during the most recent period, has not been comprehensively studied using panel data techniques.
A contribution to the empirics of food price behavior: the case of rice price dynamics in Italy
Authors: Barboza Gustavo , Gavinelli Laura , Pede Valerien , Mazzucchelli Alice , Di Gregorio Angelo
Published: September 2020

Purpose

The purpose is to detect the nonlinearity wholesale rice price formation process in Italy in the 1995–2017 period.

Design/methodology/approach

A nonlinear smooth transition autoregressive (STAR)-type dynamics model is used.

Findings

Wholesale rice prices are significantly affected by variations in the international price of rice as well as variations in Arborio price.

Research limitations/implications

The limitations include policy recommendations for the production and commercialization of rice in Italy.

Practical implications

Understanding rice pricing dynamics and nonlinearity behavior is pivotal for the survival of the entire European and Italian rice supply chain.

Originality/value

In the extant literature, no evidence exists on non-linearity of rice prices in Italy.
The COVID-19 crisis and sustainability in the hospitality industry
Authors: Jones Peter , Comfort Daphne
Published: September 2020

Purpose

This paper offers some reflections on changes in the relationships between sustainability and the hospitality industry following the onset of the Coronavirus Disease 2019 (COVID-19) crisis. (Covid-19 is officially a pandemic, but the term “COVID-19 crisis” is used throughout this paper because the authors feel that it captures the wider impacts of the crisis, rather than just focussing on the disease itself).

Design/methodology/approach

The paper describes the COVID-19 crisis, emphasises the role of hospitality in economic and social life and reviews how the crisis has changed the relationships between sustainability and the hospitality industry.

Findings

The paper reveals the dramatic effect the crisis has had on sustainability in the hospitality industry. That said, though the crisis has offered a vision of a more sustainable future, this vision may pose a major challenge for the industry and for many of its traditional customers.

Research limitations/implications

The paper outlines some of the theoretical, operational, strategic and research implications of the crisis for the hospitality industry and for hospitality scholars.

Originality/value

This paper provides a reflective review of changes in the relationships between sustainability and the hospitality industry following the onset of COVID-19.
Students' choice of international branch campus in Malaysia: a gender comparative study
Authors: Sim Adriel K.S. , Tan Kim-Lim , Sia Joseph Kee-Ming , Hii Ivy S.H.
Published: September 2020

Purpose

In the last decade, female students' enrolment in higher education has experienced significant growth. However, male and female students still differ in criteria set of choosing higher education institutions. While several studies have been disentangled in developed countries in analyzing gender differences in pursuing higher education, a similar area of studies conducted in developing countries is scarce. The purpose of this study is to examine gender differences and the factors that influence first-year students' choice of higher education in a developing country.

Design/methodology/approach

The study involved 575 students who were either enrolled in an undergraduate or foundation program of an international branch campus. We tested the hypotheses using partial least squares multigroup analysis (PLS-MGA).

Findings

Our results revealed that graduate employability, information sources, program characteristics, institution characteristics and campus safety were influential factors affecting the students' institutional choice. The MGA results also indicated that gender differences exist in selecting higher education institutions. Male students are more strongly influenced by information sources such as family, friends, media compared with female students.

Originality/value

Very few international branch campus choice studies explore gender differences in developing countries. This study enriches the current literature of institutional choice through the lens of an Asian developing country and extends the discourse regarding the role of gender in influencing students' institutional choice, of which they are commonly overlooked in most literature. The study has significant implications for student recruitment managers in higher education institution to develop marketing strategies targeting to potential male and female students.