bluuebunny/crossref_metadata_2025_split huggingface dataset:
The interaction between a parasite and sub-optimal temperatures contributes to honey bee decline
Authors: Frizzera Davide , Andreuzza Laura , Boaro Giulia , D’Agaro Mauro , Del Fabbro Simone , Zanni Virginia , Annoscia Desiderato , Nazzi Francesco 
Published: July 2021

AbstractGlobal insect decline and, in particular, honey bee colony losses are related to multiple stress factors, including landscape deterioration, pollution, parasites and climate change. However, the implications of the interaction among different stress factors for insect health are still poorly understood; in particular, little is known on how challenging environmental conditions can influence the impact of parasites. Here we exploited the honey bee as a model system to approach this problem and carried out extensive lab and field work aiming at assessing how suboptimal temperatures and parasitic challenges can alter the homeostatic balance of individual bees and the whole colony, leading to individual death and colony collapse.We found that mite infestation further than increasing the mortality of bees, induces an anorexia that in turn reduces the capacity of bees to thermoregulate, thus exposing them to the detrimental effect of lower temperatures. This, in turn, has important implications for the colony as a whole. The results highlight the role that abiotic factors can have in shaping the effect of parasitic challenges on honey bees. Furthermore, the multilevel and holistic approach adopted here can represent a useful template for similar studies on other insect species, which are particularly urgent in view of climate change and the continuous pressure of natural and exotic parasites on insect populations.
Context dependency of nucleotide probabilities and variants in human DNA
Authors: Liang Yuhu , Grønbæk Christian , Fariselli Piero , Krogh Anders 
Published: July 2021

AbstractBackgroundGenomic DNA has been shaped by mutational processes through evolution. The cellular machinery for error correction and repair has left its marks in the nucleotide composition along with structural and functional constraints. Therefore, the probability of observing a base in a certain position in the human genome is highly context-dependent.ResultsHere we develop context-dependent nucleotide models. We first investigate models of nucleotides conditioned on sequence context. We develop a bidirectional Markov model that use an average of the probability from a Markov model applied to both strands of the sequence and thus depends on up to 14 bases to each side of the nucleotide. We show how the genome predictability varies across different types of genomic regions. Surprisingly, this model can predict a base from its context with an average of more than 50% accuracy. For somatic variants we show a tendency towards higher probability for the variant base than for the reference base. Inspired by DNA substitution models, we develop a model of mutability that estimates a mutation matrix (called the alpha matrix) on top of the nucleotide distribution. The alpha matrix can be estimated from a much smaller context than the nucleotide model, but the final model will still depend on the full context of the nucleotide model. With the bidirectional Markov model of order 14 and an alpha matrix dependent on just one base to each side, we obtain a model that compares well with a model of mutability that estimates mutation probabilities directly conditioned on three nucleotides to each side. For somatic variants in particular, our model fits better than the simpler model. Interestingly, the model is not very sensitive to the size of the context for the alpha matrix.ConclusionsOur study found strong context dependencies of nucleotides in the human genome. The best model uses a context of 14 nucleotides to each side. Based on these models, a substitution model was constructed that separates into the context model and a matrix dependent on a small context. The model fit somatic variants particularly well.
Groping in the fog: soaring migrants exhibit wider scatter in flight directions and respond differently to wind under low visibility conditions
Authors: Becciu Paolo , Panuccio Michele , Dell’Omo Giacomo , Sapir Nir 
Published: July 2021

AbstractAtmospheric conditions are known to affect flight propensity, behaviour during flight, and migration route in birds. Yet, the effects of fog have only rarely been studied although they could disrupt orientation and hamper flight. Fog could limit the visibility of migrating birds such that they might not be able to detect landmarks that guide them during their journey. Soaring migrants modulate their flight speed and direction in relation to the wind vector to optimize the cost of transport. Consequently, landmark-based orientation, as well as adjustments of flight speed and direction in relation to wind conditions, could be jeopardized when flying in fog. Using a radar system operated in a migration bottleneck (Strait of Messina, Italy), we studied the behaviour of soaring birds under variable wind and fog conditions over two consecutive springs (2016 and 2017), discovering that migrating birds exhibited a wider scatter of flight directions and responded differently to wind under fog conditions. Birds flying through fog deviated more from the mean migration direction and increased their speed with increasing crosswinds. In addition, airspeed and groundspeed increased in the direction of the crosswind, causing the individuals to drift laterally. Our findings represent the first quantitative empirical evidence of flight behaviour changes when birds migrate through fog and explain why low visibility conditions could risk their migration journey.
A transmissible γδ intraepithelial lymphocyte hyperproliferative phenotype is associated with the intestinal microbiota and confers protection against acute infection
Authors: Jia Luo , Wu Guojun , Alonso Sara , Zhao Cuiping , Lemenze Alexander , Lam Yan Y. , Zhao Liping , Edelblum Karen L. 
Published: July 2021

AbstractIntraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) serve as a first line of defense against luminal microbes. Although the presence of an intact microbiota is dispensable for γδ IEL development, several microbial factors contribute to the maintenance of this sentinel population. However, whether specific commensals influence population of the γδ IEL compartment under homeostatic conditions has yet to be determined. We identified a novel γδ IEL hyperproliferative phenotype that arises early in life and is characterized by expansion of multiple Vγ subsets. Horizontal transfer of this hyperproliferative phenotype to mice harboring a phenotypically normal γδ IEL compartment was prevented following antibiotic treatment, thus demonstrating that the microbiota is both necessary and sufficient for the observed increase in γδ IELs. Further, we identified a group of unique gut bacteria represented by 5 amplicon sequence variants (ASV) which are strongly associated with γδ IEL expansion. Using intravital microscopy, we find that hyperproliferative γδ IELs also exhibit increased migratory behavior leading to enhanced protection against bacterial infection. These findings reveal that transfer of a specific group of commensals can regulate γδ IEL homeostasis and immune surveillance, which may provide a novel means to reinforce the epithelial barrier.
A workflow for rapid unbiased quantification of fibrillar feature alignment in biological images
Authors: Marcotti Stefania , Freitas Deandra Belo de , Troughton Lee D , Kenny Fiona N , Shaw Tanya , Stramer Brian M , Oakes Patrick W 
Published: July 2021

ABSTRACTMeasuring the organisation of the cellular cytoskeleton and the surrounding extracellular matrix (ECM) is currently of wide interest as changes in both local and global alignment can highlight alterations in cellular functions and material properties of the extracellular environment. Different approaches have been developed to quantify these structures, typically based on fibre segmentation or on matrix representation and transformation of the image, each with its own advantages and disadvantages.Here we presentAFT - Alignment by Fourier Transform, a workflow to quantify the alignment of fibrillar features in microscopy images exploiting 2D Fast Fourier Transforms (FFT). Using pre-existing datasets of cell and ECM images, we demonstrate our approach and compare and contrast this workflow with two other well-known ImageJ algorithms to quantify image feature alignment. These comparisons reveal thatAFThas a number of advantages due to its grid-based FFT approach. 1) Flexibility in defining the window and neighbourhood sizes allows for performing a parameter search to determine an optimal length scale to carry out alignment metrics. This approach can thus easily accommodate different image resolutions and biological systems. 2) The length scale of decay in alignment can be extracted by comparing neighbourhood sizes, revealing the overall distance that features remain anisotropic. 3) The approach is ambivalent to the signal source, thus making it applicable for a wide range of imaging modalities and is dependent on fewer input parameters than segmentation methods. 4) Finally, compared to segmentation methods, this algorithm is computationally inexpensive, as high-resolution images can be evaluated in less than a second on a standard desktop computer. This makes it feasible to screen numerous experimental perturbations or examine large images over long length scales.Implementation is made available in both MATLAB and Python for wider accessibility, with example datasets for single images and batch processing. Additionally, we include an approach to automatically search parameters for optimum window and neighbourhood sizes, as well as to measure the decay in alignment over progressively increasing length scales.
Cross immunity protection and antibody dependent enhancement: A distributed delay dynamic model
Authors: Steindorf Vanessa , Oliva Sergio , Wu Jianhong 
Published: July 2021

AbstractDengue fever is endemic in tropical and sub-tropical countries, and some of the important features of Dengue fever spread continues to pose challenges for mathematical modelling. Here, we propose a system of integro-differential equations (IDE) to study the disease transmission dynamics that involves multiserotypes and cross immunity. Our main objective is to incorporate and analyze the effect of a general time delay term describing acquired cross immunity protection and the effect of antibody dependent enhancement (ADE), both characteristics of Dengue fever. We perform qualitative analysis of the model and obtain results to show the stability of the epidemiologically important steady solutions that is completely determined by the basic reproduction number and the invasion reproduction number. We establish the global dynamics, by constructing suitable Lyapunov functions. We also conduct some numerical experiments to illustrate bifurcation structures, indicating the occurrence of periodic oscillations for specific range of values of a key parameter representing the ADE.
OPUS-Rota4: A Gradient-Based Protein Side-Chain Modeling Framework Assisted by Deep Learning-Based Predictors
Authors: Xu Gang , Wang Qinghua , Ma Jianpeng 
Published: July 2021

AbstractAccurate protein side-chain modeling is crucial for protein folding and protein design. In the past decades, many successful methods have been proposed to address this issue. However, most of them depend on the discrete samples from the rotamer library, which may have limitations on their accuracies and usages. In this study, we report an open-source toolkit for protein side-chain modeling, named OPUS-Rota4. It consists of three modules: OPUS-RotaNN2, which predicts protein side-chain dihedral angles; OPUS-RotaCM, which measures the distance and orientation information between the side chain of different residue pairs; and OPUS-Fold2, which applies the constraints derived from the first two modules to guide side-chain modeling. In summary, OPUS-Rota4 adopts the dihedral angles predicted by OPUS-RotaNN2 as its initial states, and uses OPUS-Fold2 to refine the side-chain conformation with the constraints derived from OPUS-RotaCM. In this case, we convert the protein side-chain modeling problem into a side-chain contact map prediction problem. OPUS-Fold2 is written in Python and TensorFlow2.4, which is user-friendly to include other differentiable energy terms into its side-chain modeling procedure. In other words, OPUS-Rota4 provides a platform in which the protein side-chain conformation can be dynamically adjusted under the influence of other processes, such as protein-protein interaction. We apply OPUS-Rota4 on 15 FM predictions submitted by Alphafold2 on CASP14, the results show that the side chains modeled by OPUS-Rota4 are closer to their native counterparts than the side chains predicted by Alphafold2.
Neural and computational processes of accelerated perceptual awareness and decisions: A 7T fMRI Study
Authors: Kalhan Shivam , McFadyen Jessica , Tsuchiya Naotsugu , Garrido Marta I. 
Published: July 2021

AbstractRapidly detecting salient information in our environments is critical for survival. Visual processing in subcortical areas like the pulvinar and amygdala have been shown to facilitate unconscious processing of salient stimuli. It is unknown, however, if and how these areas might interact with cortical networks to facilitate faster conscious perception of salient stimuli. Here we investigated these neural processes using 7T functional Magnetic Resonance Imaging (fMRI) in concert with computational modelling while participants (n = 32) engaged in a breaking continuous flash suppression paradigm (bCFS) in which fearful and neutral faces are initially suppressed from conscious perception but then eventually “breakthrough” into awareness. We found that participants reported faster breakthrough times for fearful faces compared to neutral faces. Drift-diffusion modelling suggested that perceptual evidence was accumulated at a faster rate for fearful faces compared to neutral faces. For both neutral and fearful faces, faster response times coincided with greater activity in the amygdala (specifically within its subregions, including superficial, basolateral and amygdalo-striatal transition area) and the insula. Faster rates of evidence accumulation coincided with greater activity in frontoparietal regions and the occipital lobe, as well as the amygdala. Overall, our findings suggest that hastened perceptual awareness of salient stimuli recruits the amygdala and, more specifically, is driven by accelerated evidence accumulation in fronto-parietal and visual areas. In sum, we have uncovered and mapped distinct neural computations that accelerate perceptual awareness of visually suppressed faces.
Transcriptional Landscape of Ectomycorrhizal Fungi and Their Host Provide Insight into N Uptake from Forest Soil
Authors: Rivera Pérez Carmen Alicia , Janz Dennis , Schneider Dominik , Daniel Rolf , Polle Andrea 
Published: July 2021

ABSTRACTMineral nitrogen (N) is a major nutrient showing strong fluctuations in the environment due to anthropogenic activities. Acquisition and translocation of N to forest trees is achieved by highly diverse ectomycorrhizal fungi (EMF) living in symbioses with their host roots. Here, we examined colonized root tips to characterize the entire root-associated fungal community by DNA metabarcoding-Illumina sequencing of the fungal ITS2 molecular marker and used RNA sequencing to target metabolically active fungi and the plant transcriptome after N application. The study was conducted with beech (Fagus sylvaticaL), a dominant tree species in central Europe, grown in native forest soil. We demonstrate strong enrichment of15N from nitrate or ammonium in the ectomycorrhizal roots by stable isotope labeling. The relative abundance of the EMF members in the fungal community was correlated with their transcriptional abundances. The fungal metatranscriptome covered KEGG and KOG categories similar to model fungi and did not reveal significant changes related to N metabolization but species-specific transcription patterns, supporting trait stability. In contrast to the resistance of the fungal metatranscriptome, the transcriptome of the host exhibited dedicated nitrate- or ammonium-responsive changes with upregulation of transporters and enzymes required for nitrate reduction and drastic enhancement of glutamine synthetase transcript levels, indicating channeling of ammonium into the pathway for plant protein biosynthesis. Our results support that self-composed fungal communities associated with tree roots buffer nutritional signals in their own metabolism but do not shield plants from high environmental N.IMPORTANCEAlthough EMF are well known for their role in supporting tree N nutrition, the molecular mechanisms underlying N flux from the soil solution into the host through the ectomycorrhizal pathway remain widely unknown. Furthermore, ammonium and nitrate availability in the soil solution is subject to constant oscillations that create a dynamic environment for the tree roots and associated microbes during N acquisition. Therefore, it is important to understand how root-associated mycobiomes and the tree roots handle these fluctuations. We studied the response of the symbiotic partners by screening their transcriptomes after a sudden environmental flux of nitrate or ammonium. We show that the fungi and the host respond asynchronously, with the fungi displaying resistance to increased nitrate or ammonium, and the host dynamically metabolizing the supplied N sources. This study provides insights into the molecular mechanisms of the symbiotic partners operating under N enrichment in a multidimensional symbiotic system.
Coordinated activation of both TGFβ and BMP canonical pathways regulates autophagy and tissue regeneration in acetaminophen induced liver injury
Authors: Stavropoulos Athanasios , Divolis Georgios , Manioudaki Maria , Gavriil Ariana , Kloukina Ismini , Perrea Despina N. , Sountoulidis Alexandros , Ford Ethan , Doulou Athanasia , Apostolidou Anastasia , Katsantoni Elena , Ritvos Olli , Germanidis Georgios , Xilouri Maria , Sideras Paschalis 
Published: July 2021

AbstractTransforming Growth Factor-βs (TGFβs)/Activins and Bone Morphogenetic Proteins (BMPs) have been implicated in numerous aspects of hepatic pathophysiology. However, the way by which hepatocytes integrate and decode the interplay between the TGFβ/Activin and BMP branches in health and disease is still not fully understood. To address this, TGFβ/BMP Smad- responsive double transgenic reporter mice were generated and utilized to map patterns of TGFβ- and/or BMP-pathway activation during acetaminophen- induced liver injury. TGFβ signaling was blocked either pharmacologically or by Smad7 over-expression and the transcriptomes of canonical TGFβ- and/or BMP4-treated hepatospheres and Smad7-treated livers were analyzed to highlight TGFβ-superfamily-regulated pathways and processes. Acetaminophen administration led to dynamically evolving, stage- and context-specific, patterns of hepatic TGFβ/Activin and BMP-reporter expression. TGFβ-superfamily signaling was activated in an autophagy prone zone at the borders between healthy and injured tissue. Inhibition of TGFβ-superfamily signaling attenuated autophagy, exacerbated liver histopathology, and finally led to accelerated tissue-recovery. Hallmarks of this process were the paraptosis-like cell death and the attenuation of immune and reparatory cell responses. Transcriptomic analysis highlighted autophagy as a prominent TGFβ1- and BMP4-regulated process and recognizedTrp53inp2as the top TGFβ-superfamily-regulated autophagy-related gene. Collectively, these findings implicate the coordinated activation of both canonical TGFβ-superfamily signalling branches in balancing autophagic response and tissue-reparatory and -regenerative processes upon acetaminophen-induced hepatotoxicity, highlighting opportunities and putative risks associated with their targeting for treatment of hepatic diseases.
EZH2 inhibition enhances TRAIL responses in multiple myeloma but not in quiescent cells
Authors: Arhoma Amal , Southan Jenny , Chantry Andrew D , Haywood-Small Sarah L , Cross Neil A 
Published: July 2021

AbstractMultiple Myeloma is a plasma cell malignancy for which there is currently no cure, despite many novel therapies. TRAIL (Tumour necrosis factor-related apoptosis inducing ligand) is a promising anti-tumour agent although TRAIL-insensitive cells readily emerge when used as a single agent and its effects are limited due to many TRAIL-resistant cells which emerge soon after treatment. EZH2 is a H3K27 histone methyltransferase found to be overexpressed in many cancers including Multiple Myeloma. We tested the hypothesis that epigenetic reprogramming using the EZH2 inhibitor GSK343 would enhance TRAIL sensitivity, overcome TRAIL resistance, and target TRAIL-resistant quiescent cell populations. We show that GSK343 is a potent TRAIL sensitiser in TRAIL-sensitive RPMI 8226, NCI-H 929 and U266, and in TRAIL-resistant OPM-2 and JJN3, the latter showing very potent synergistic induction of apoptosis, primarily via caspase-8 activation but also via caspase-9. GSK343-enhancement of TRAIL responses was further enhanced in a 3D cell culture model of Multiple Myeloma in NCI-H 929 and U266. We show that in TRAIL-resistant sub-populations of Multiple Myeloma cells, GSK343 responses were completely attenuated in RPMI 8226 although synergistic enhancement of apoptosis was observed in NCI-H 929. Furthermore, following isolation of PKH26Hi quiescent cell populations, TRAIL responses and enhancement of TRAIL responses by GSK343 were completely attenuated. These studies show that EZH2 inhibition enhances TRAIL responses both in TRAIL-sensitive and TRAIL-resistant MM cell lines suspension culture and also in 3D cell culture to model the semi-solid Multiple Myeloma lesions in bone. Pre-existing TRAIL resistance was also enhanced by EZH2, and although synergistic enhancement of TRAIL responses by GSK343 was seen in NCI-H 929, responses were completely lost in TRAIL-resistant RPMI 8226 and also in quiescent cells. These studies highlight that although EZH2 inhibitors enhance TRAIL responses, acquired TRAIL resistance, and the presence of quiescent cells may mediate TRAIL-insensitivity in response to GSK343.