bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput tuning of ovarian cancer spheroids for on-chip invasion assays
Authors: Chen Changchong , He Yong , Lopez Elliot , Carreiras Franck , Yamada Ayako , Schanne-Klein Marie-Claire , Lambert Ambroise , Chen Yong , Aimé Carole 
Published: November 2021

AbstractWe developed an invasion assay by using microfabricated culture devices. First, ovarian tumor spheroids were generated with a culture patch device consisting of an agarose membrane formed with a honeycomb microframe – thepatch– and gelatin nanofiber backbone. By changing the dimensions of the honeycomb compartments we were able to control the number of cells and size of the spheroids. When the spheroids were placed on a patch coated with a thin membrane of fibrillary type I collagen, spheroid disruption was observed due to substrate induced cell migration. This process is straightforward and should be applicable to other cancer types, as well as assays under microfluidic conditions, thereby holding the potential for use in tumor modeling and anti-cancer drug development.
A scale-invariant perturbative approach to study information communication in dynamic brain networks
Authors: Mohan Varun Madan , Banerjee Arpan 
Published: November 2021

AbstractHow communication among neuronal ensembles shapes functional brain dynamics at the large scale is a question of fundamental importance to Neuroscience. To date, researchers have primarily relied on two alternative ways to address this issue 1) in-silico neurodynamical modelling of functional brain dynamics by choosing biophysically inspired non-linear systems, interacting via a connection topology driven by empirical data; and 2) identifying topological measures to quantify network structure and studying them in tandem with functional metrics of interest, e.g. co-variation of time series in brain regions from fast (EEG/ MEG) and slow (fMRI) timescales. While the modelling approaches are limited in scope to only scales of the nervous system for which dynamical models are well defined, the latter approach does not take into account how the network architecture and intrinsic regional node dynamics contribute together to inter-regional communication in the brain. Thus, developing a generalized scale-invariant measure of interaction between network topology and constituent regional dynamics can potentially resolve how transmission of perturbations in brain networks alter function e.g. by neuropathologies, or the intervention strategies designed to mitigate them. In this work, we introduce a recently developed theoretical perturbative framework in network science into a neuroscientific framework, to conceptualize the interaction of regional dynamics and network architecture in a quantifiable manner. This framework further provides insights into the information communication contributions of putative regions and sub-networks in the brain, irrespective of the observational scale of the phenomenon (firing rates to BOLD fMRI time series). The proposed approach can directly quantify network-dynamical interactions without reliance on a specific class of models or response characteristics: linear/nonlinear. By simply gauging the asymmetries in responses to perturbations, we obtain insights into the significance of regions in communication and their influence over the rest of the network. Moreover, coupling perturbations with functional lesions can also answer which regions contribute the most to information spread: a quantity termed Flow. The simplicity of the proposed technique allows translation to an experimental setting where the response asymmetries and flow can inversely act as a window into the dynamics of regions. For proof-of-concept, we apply the perturbative approach on in-silico data generated for human resting state network dynamics, using different established dynamical models that mimic empirical observations. We also apply the perturbation approach at the level of large scale Resting State Networks (RSNs) to gauge the range of network-dynamical interactions in mediating information flow across brain regions.
Synchrony and idiosyncrasy in the gut microbiome of wild baboons
Authors: Björk Johannes R. , Dasari Mauna R. , Roche Kim , Grieneisen Laura , Gould Trevor J. , Grenier Jean-Christophe , Yotova Vania , Gottel Neil , Jansen David , Gesquiere Laurence R. , Gordon Jacob B. , Learn Niki H. , Wango Tim L. , Mututua Raphael S. , Warutere J. Kinyua , Siodi Long’ida , Mukherjee Sayan , Barreiro Luis B. , Alberts Susan C. , Gilbert Jack A. , Tung Jenny , Blekhman Ran , Archie Elizabeth A. 
Published: November 2021

AbstractHuman gut microbial dynamics are highly individualized, making it challenging to link microbiota to health and to design universal microbiome therapies. This individuality is typically attributed to variation in host genetics, diets, environments, and medications, but it could also emerge from fundamental ecological forces that shape microbiota more generally. Here we leverage extensive gut microbial time series from wild baboons—hosts who experience little interindividual dietary and environmental heterogeneity—to test whether gut microbial dynamics are synchronized across hosts or largely idiosyncratic. Despite their shared lifestyles, baboon microbiome dynamics were only weakly synchronized. The strongest synchrony occurred among baboons living in the same social group, likely because group members range over the same habitat and simultaneously encounter the same sources of food and water. However, this synchrony was modest compared to each host’s personalized dynamics. Indeed, host-specific factors, especially host identity, explained 10 times the deviance in longitudinal microbial dynamics, compared to factors shared across hosts. These results contribute to mounting evidence that highly idiosyncratic gut microbiomes are not an artifact of modern human environments, and that synchronizing forces in the gut microbiome (e.g., shared environments, diets, and microbial dispersal) are often not strong enough to overwhelm drivers of microbiome personalization, including host genetics, priority effects, horizontal gene transfer, and functional redundancy.
Social preference in rats not impacted by posterior parietal activity despite overall changes in familiarity-based social behavior
Authors: Wise Taylor B. , Burwell Rebecca D. , Templer Victoria L. 
Published: November 2021

AbstractRecent literature points to a potential link between the evolution of complex social behavior and the posterior parietal cortex (PPC) in primates including humans (Parkinson & Wheatley, 2013). Thus far, this theory has been overlooked in other highly social animals that may have also evolved due to social selective pressures. In rodents, there is limited knowledge on the involvement of the PPC on sociality, and most studies of such behavior are limited to understanding social preference. We investigated the role of the PPC through two experiments using the 3-Chamber Sociability and Social Novelty test in rats (Crawley, 2004). In Experiment 1, we used a standard 3-Chamber paradigm, which included two novel demonstrators. In Experiment 2, this paradigm was altered to increase the difference in familiarity between demonstrators such that one demonstrator was highly familiar to the subject and the other was entirely novel. Rats with pre-testing permanent neurotoxic lesions were compared to sham surgery control rats, and the same rats were used for both experiments. Experiments 1 and 2 showed that both groups of rats preferred general social interaction, suggesting no deficit in sociability following PPC damage, regardless of demonstrator identity. Further, experimental and control rats showed similar levels of novelty preference following PPC damage, with novelty preferences increasing in Experiment 2. We argue that heightened novelty preference in Experiment 2 may reflect the increased difference in familiarity between demonstrators. Within the confines of the 3-Chamber task, our results suggest that PPC function was not required for general sociability or social novelty recognition. Because the PPC is implicated in abstract cognition, we argue that existing social tests in rodents may not adequately measure the complex cognitive capacities thought to be supported by the PPC. Future studies should investigate the role of the PPC in social cognition by employing behavioral tasks that require higher cognitive demand rather than testing inherent preference for social partners. Outside of our investigation of the PPC, these results show that social novelty preference can be manipulated through changes in familiarity of demonstrators, and that rats can discriminate others’ social identities.
Genome of the bi-annual Rio Pearlfish (Nematolebias whitei), a killifish model species for Eco-Evo-Devo
Authors: Thompson Andrew W. , Wojtas Harrison , Davoll Myles , Braasch Ingo 
Published: November 2021

AbstractThe Rio Pearlfish Nematolebias whitei is a bi-annual killifish species inhabiting seasonal pools of the Rio de Janeiro region that dry twice per year. Embryos enter dormant diapause stages in the soil, waiting for the inundation of the habitat which triggers hatching and commencement of a new life cycle. This species represents a convergent, independent origin of annualism from other emerging killifish model species. While some transcriptomic datasets are available for Rio Pearlfish, thus far a sequenced genome has been unavailable. Here we present a high quality, 1.2Gb chromosome-level genome assembly, genome annotations and a comparative genomic investigation of the Rio Pearlfish as representative of a vertebrate clade that evolved environmentally-cued hatching. We show conservation of 3-D genome structure across teleost fish evolution, developmental stages, tissues and cell types. Our analysis of mobile DNA shows that Rio Pearlfish, like other annual killifishes, possesses an expanded transposable element profile with implications for rapid aging and adaptation to harsh conditions. We use the Rio Pearlfish genome to identify its hatching enzyme gene repertoire and the location of the hatching gland, a key first step in understanding the developmental genetic control of hatching. The Rio Pearlfish genome expands the comparative genomic toolkit available to study convergent origins of seasonal life histories, diapause, and rapid aging phenotypes. We present the first set of genomic resources for this emerging model organism, critical for future functional genetic and multi-omic explorations of “Eco-Evo-Devo” phenotypes in resilience and adaptation to extreme environments.Significance:Seasonal or annual killifishes are emerging models for aging, life history adaptions to extreme environments, and ecological evolutionary developmental biology (Eco-Evo-Devo). Most studies have thus far focused on the African turquoise killifish Nothobranchius furzeri and the South American Austrofundulus limneaus. We sequenced and analyzed the genome of the Rio Pearlfish Nematolebias whitei from the Rio de Janeiro region, a seasonal species representing a convergent origin of seasonality from other sequenced killifish species, strengthening the comparative potential of Aplocheiloid killifishes as a model clade for the comparative and functional genomics of animal resilience to environmental change.
Measurements and simulations of microtubule growth imply strong longitudinal interactions and reveal a role for GDP on the elongating end
Authors: Cleary Joseph M. , Kim Tae , Cook Annan S. I. , Hancock William O. , Rice Luke M. 
Published: November 2021

AbstractMicrotubule polymerization dynamics result from the biochemical interactions of αβ-tubulin with the polymer end, but a quantitative understanding has been challenging to establish. We used interference reflection microscopy to make improved measurements of microtubule growth rates and growth fluctuations in the presence and absence of GTP hydrolysis. In the absence of GTP hydrolysis, microtubules grew steadily with very low fluctuations. These data were best described by a computational model implementing slow assembly kinetics, such that the rate of microtubule elongation is primarily limited by the rate of αβ-tubulin associations. With GTPase present, microtubules displayed substantially larger growth fluctuations than expected based on the no GTPase measurements. Our modeling showed that these larger fluctuations occurred because exposure of GDP-tubulin on the microtubule end transiently ‘poisoned’ growth, yielding a wider range of growth rate compared to GTP only conditions. Our experiments and modeling point to slow association kinetics (strong longitudinal interactions), such that drugs and regulatory proteins that alter microtubule dynamics could do so by modulating either the association or dissociation rate of tubulin from the microtubule tip. By causing slower growth, exposure of GDP tubulin at the growing microtubule end may be an important early event determining catastrophe.
A new early-branching armoured dinosaur from the Lower Jurassic of southwestern China
Authors: Yao Xi , Barrett Paul M , Yang Lei , Xu Xing , Bi Shundong 
Published: November 2021

AbstractThe early evolutionary history of the armoured dinosaurs (Thyreophora) is obscured by its patchily distributed fossil record and by conflicting views on the relationships of its Early Jurassic representatives. Here, we describe an early-diverging thyreophoran from the Lower Jurassic Fengjiahe Formation of Yunnan Province, China, on the basis of an associated partial skeleton that includes skull, axial, limb and armour elements. It can be diagnosed as a new taxon based on numerous cranial and postcranial autapomorphies and is further distinguished from all other thyreophorans by a unique combination of character states. Although the robust postcranium is similar to that of more deeply nested ankylosaurs and stegosaurs, phylogenetic analysis recovers it as either the sister taxon of Emausaurus or of the clade Scelidosaurus+Eurypoda. This new taxon, XXXX XXXX, represents the first valid thyreophoran dinosaur to be described from the Early Jurassic of Asia and confirms the rapid geographic spread and diversification of the clade after its first appearance in the Hettangian. Its heavy build and distinctive armour also hint at previously unrealised morphological diversity early in the clade’s history.
Identifying cell-to-cell variability in internalisation using flow cytometry
Authors: Browning Alexander P , Ansari Niloufar , Drovandi Christopher , Johnston Angus P R , Simpson Matthew J , Jenner Adrianne L 
Published: November 2021

SummaryBiological heterogeneity is a primary contributor to the variation observed in experiments that probe dynamical processes, such as internalisation. Given that internalisation is a critical process by which many therapeutics and viruses reach their intracellular site of action, quantifying cell-to-cell variability in internalisation is of high biological interest. Yet, it is common for studies of internalisation to neglect cell-to-cell variability. We develop a simple mathematical model of internalisation that captures the dynamical behaviour, cell-to-cell variation, and extrinsic noise introduced by flow cytometry. We calibrate our model through a novel distribution-matching approximate Bayesian computation algorithm to flow cytometry data of internalisation of anti-transferrin receptor antibody in a human B-cell lymphoblastoid cell line. Our model reproduces experimental observations, identifies cell-to-cell variability in the internalisation and recycling rates, and, importantly, provides information relating to inferential uncertainty. Given that our approach is agnostic to sample size and signal-to-noise ratio, our modelling framework is broadly applicable to identify biological variability in single-cell data from internalisation assays and similar experiments that probe cellular dynamical processes.
A Hybrid Communication Pattern in Human Brain Structural Network Revealed by Evolutionary Computation
Authors: Liang Quanmin , Ma Junji , Chen Xitian , Dai Zhengjia , Lin Ying 
Published: November 2021

AbstractThe human brain functional connectivity network (FCN) is constrained and shaped by the communication processes in the structural connectivity network (SCN). The underlying communication mechanism thus becomes a critical issue for understanding the formation and organization of the FCN. A number of communication models supported by different routing strategies have been proposed, with shortest path (SP), random diffusion (DIF), and spatial navigation (NAV) as the most typical, respectively requiring network global knowledge, local knowledge, and both for path seeking. Yet these models all assumed every brain region to use one routing strategy uniformly, ignoring convergent evidence that supports the regional heterogeneity in both terms of biological substrates and functional roles. In this regard, the current study developed a hybrid communication model that allowed each brain region to choose a routing strategy from SP, DIF, and NAV independently. A genetic algorithm was designed to uncover the underlying region-wise hybrid routing strategy (namely HYB). The HYB was found to outperform the three typical routing strategies in predicting FCN and facilitating robust communication. Analyses on HYB further revealed that brain regions in lower-order functional modules inclined to route signals using global knowledge, while those in higher-order functional modules preferred DIF that requires only local knowledge. Compared to regions that used global knowledge for routing, regions using DIF had denser structural connections, participated in more functional modules, but played a less dominant role within modules. Together, our findings further evidenced that hybrid routing underpins efficient SCN communication and locally heterogeneous structure-function coupling.
Tetraspanin Cd9b plays a role in fertility in zebrafish
Authors: Greaves S , Marsay KS , Monk PN , Roehl H , Partridge LJ 
Published: November 2021

AbstractIn mice, CD9 expression on the egg is required for efficient sperm-egg fusion and no effects on ovulation or male fertility are observed in CD9 null animals. Here we show thatcd9bKO zebrafish also appear to have fertility defects. In contrast to mice, fewer eggs were laid bycd9bKO zebrafish pairs and, of the eggs laid, a lower percentage were fertilised.In vitrofertilization (IVF) was used to demonstrate that factors such as courting behaviour, adult size and mate choice were not causing the unexpected decrease in clutch size. The decrease in egg numbers could be rescued by exchanging eithercd9bKO partner, male or female, for a wildtype (WT) partner. However, the fertilisation defect could only be rescued by crossing acd9bKO female with a WT male. Our results indicate that Cd9b has several roles in fish fertility, affecting both clutch size and egg fertilisation.Highlightscd9bmutant pairs lay fewer eggs and of the eggs laid, fewer are fertilised.Mutation incd9bdoes not affect primordial germ cell number or migration.Reduction in number of eggs and fertility is not due to courting behaviour, fish size or mate choice.cd9bmutation in either gender affects the number of eggs laid.Mutation ofcd9bin the males affects fertilisation efficiency but mutation ofcd9bin the females does not.
Survival of Campylobacter jejuni in Amoebae enhances subsequent invasion of mammalian cells
Authors: Nasher Fauzy , Wren Brendan W. 
Published: November 2021

AbstractThe ubiquitous unicellular eukaryote, Acanthamoeba, is known to play a role in the survival and dissemination of Campylobacter jejuni. C. jejuni is the leading cause of bacterial foodborne gastroenteritis world-wide and is a major public health problem. The ability of C. jejuni to interact and potentially invade epithelial cells is thought to be key for disease development in humans. We examined C. jejuni grown under standard laboratory conditions,11168HCBA with that harvested from within Acanthamoeba castellanii (11168HAC/CBA) or Acanthamoeba polyphaga (11168HAP/CBA), and compared their ability to invade different cell lines. C. jejuni harvested from within amoebae had a ∼3.7-fold increase in invasiveness into T84 human epithelial cells and a striking ∼11-fold increase for re-entry into A. castellanii cells. We also investigated the invasiveness and survivability of six diverse representative C. jejuni strains within Acanthamoeba spp., our results confirm that invasion and survivability is likely host cell dependent. Our survival assay data led us to conclude that Acanthamoeba spp. are a transient host for C. jejuni and that survival within amoebae pre-adapts C. jejuni and enhances subsequent cell invasion. This study provides new insight into C. jejuni interactions with amoebae and its increased invasiveness potential in mammalian hosts.
Gene conversion explains elevated diversity in the immunity modulating APL1 gene of the malaria vector Anopheles funestus
Authors: Hearn Jack , Riveron Jacob M. , Irving Helen , Weedall Gareth D. , Wondji Charles S. 
Published: November 2021

AbstractThe leucine rich repeat gene APL1 is a key component of immunity to Plasmodium and other microbial pathogens in Anopheles mosquitoes. In the malaria vector Anopheles funestus the APL1 gene has four paralogues which occur along the same chromosome arm. We show that APL1 has exceptional levels of non-synonymous polymorphism across the range of An. funestus with an average πn of 0.027 versus a genome-wide average of 0.002, and πn (and πs) is consistently high in populations across Africa. The pattern of APL1 diversity was consistent between independent pooled-template and target-enrichment datasets, however no link between APL1 diversity and insecticide-resistance was observed with the phenotyped target-enrichment dataset. Two further innate immunity genes of the gambicin anti-microbial peptide family had πn/πs ratios greater than one, possibly driven by either positive or balancing selection. Cecropin antimicrobial peptides were expressed much more highly than other anti-microbial peptide genes, an observation discordant with current models of anti-microbial peptide activity. The observed APL1 diversity likely results from gene conversion between paralogs, as evidenced by shared polymorphisms, overlapping read mappings, and recombination events among paralogues. Gene conversion at APL1 versus alternative explanations is concordant with similarly elevated diversity in APL1 and TEP1 loci in An. gambiae. In contrast, the more closely related An. stephensi which also encodes a single-copy of APL1 does not show this elevated diversity. We hypothesise that a more open chromatin formation at the APL1 locus due to higher gene expression than its paralogues enhances gene conversion, and therefore increased polymorphism, at APL1.