bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraspecific variation in immune gene expression and heritable symbiont density
Authors: Nichols Holly L. , Goldstein Elliott B. , Ziabari Omid Saleh , Parker Benjamin J. 
Published: December 2020

AbstractHost genetic variation plays an important role in the structure and function of heritable microbial communities. Recent studies have demonstrated that insects use immune mechanisms to regulate heritable symbionts. Here we test the hypothesis that variation in symbiont density within hosts is linked to intraspecific differences in the immune response to harboring symbionts. We show that pea aphids (Acyrthosiphon pisum) harboring the bacterial endosymbiontRegiella insecticola(but not all other species of symbionts) suppress expression of key immune genes. We then functionally link immune suppression with symbiont density using RNAi. The pea aphid species complex is comprised of multiple reproductively-isolated host plant-adapted populations. These ‘biotypes’ have distinct patterns of heritable symbiont infections: for example, aphids from theTrifoliumbiotype are strongly associated withRegiella. Using RNAseq, we compare patterns of gene expression in response toRegiellain aphid genotypes from multiple biotypes, and we show thatTrifoliumaphids experience no immune gene suppression fromRegiellaand host symbionts at lower densities. We then generated F1 hybrids between two biotypes and found that symbiont density and immune suppression are both intermediate in hybrids. We suggest that in this system,Regiellasymbionts are suppressing aphid immune mechanisms to increase their density, but that some hosts have adapted to prevent immune suppression in order to control symbiont numbers. The specific immune mechanisms suppressed byRegiellahave been previously demonstrated to combat pathogens in aphids, and thus this work highlights the immune system’s complex dual role in interacting with both beneficial and harmful microbes.AuthorSummaryHeritable microbes are found in most insects including agriculturally and medically relevant pests. Explaining the variation in the distribution and abundance of symbionts in natural populations is critical to understanding these interactions. This work contributes to our mechanistic understanding of an important model of host-microbe symbiosis and suggests more broadly that variation in insect immune responses plays a role in intraspecific variation in host-symbiont interactions. Our work also suggests that antagonistic coevolution can play a role in host-microbe interactions even when microbes are transmitted vertically and provide a clear benefit to their hosts.
Mesophotic gorgonian corals evolve multiple times and faster than deep and shallow lineages
Authors: Sánchez Juan A. , González-Zapata Fanny L. , Prada Carlos , Dueñas Luisa F. 
Published: December 2020

1.SummaryMesophotic Coral Ecosystems (MCEs) develop on a unique environment, where abrupt environmental changes take place. Using a time-calibrated molecular phylogeny (mtDNA: mtMutS), we examined the lineage membership of mesophotic gorgonian corals (Octocorallia: Cnidaria) in comparison to shallow and deep-sea lineages of the wider Caribbean-Gulf of Mexico and the Tropical Eastern Pacific. Our results show mesophotic gorgonians originating multiple times from old deep-sea octocoral lineages, whereas shallow-water species comprise younger lineages. The mesophotic gorgonian fauna in the studied areas are related to their zooxanthellate shallow-water counterparts in only two clades (Gorgoniidae and Plexauridae), where the shallow-deep gradient could serve as a driver of diversification. Interestingly, mesophotic clades have diversified faster than either shallow or deep clades. One of this groups with fast diversification is the family Ellisellidae, a major component of the mesophotic gorgonian coral assemblage worldwide.
Mutually inclusive mechanisms of drought-induced tree mortality
Authors: Hajek Peter , Link Roman M. , Nock Charles , Bauhus Jürgen , Gebauer Tobias , Gessler Arthur , Kovach Kyle , Messier Christian , Paquette Alain , Saurer Matthias , Scherer-Lorenzen Michael , Rose Laura , Schuldt Bernhard 
Published: December 2020

AbstractAn extreme summer drought caused unprecedented tree dieback across Central Europe in 2018, highlighting the need for a better mechanistic understanding of drought-induced tree mortality. While numerous physiological risk factors have been identified, the principal mechanisms, hydraulic failure and carbon starvation, are still debated. We studied 9,435 trees from 12 temperate species planted in a diversity experiment in 2013 to assess how hydraulic traits, carbon dynamics, pest infestation, tree height and neighbourhood competition influence individual mortality risk. We observed a reduced mortality risk for trees with wider hydraulic safety margins, while a rising sugar fraction of the non-structural carbohydrate pool and bark beetle infestation were associated with higher risk. Taller trees had a lower mortality risk. The sign and magnitude of neighbourhood effects on mortality risk depended on the species-identity of the involved trees, with most species having beneficial and some having deleterious effects on their neighbours. While severe tissue dehydration causing hydraulic failure precedes drought-induced tree mortality, we show that the probability of this event depends on a series of mutually inclusive processes including pest infestation and starch depletion for osmotic adjustment, and is modulated by the size and species identity of a tree and its neighbours.
Broad transcriptomic dysregulation across the cerebral cortex in ASD
Authors: Haney Jillian R. , Wamsley Brie , Chen George T. , Parhami Sepideh , Emani Prashant S. , Chang Nathan , Hoftman Gil D. , de Alba Diego , Kale Gaurav , Ramaswami Gokul , Hartl Christopher L. , Jin Ting , Wang Daifeng , Ou Jing , Wu Ye Emily , Parikshak Neelroop N. , Swarup Vivek , Belgard T. Grant , Gerstein Mark , Pasaniuc Bogdan , Gandal Michael J. , Geschwind Daniel H. 
Published: December 2020

AbstractClassically, psychiatric disorders have been considered to lack defining pathology, but recent work has demonstrated consistent disruption at the molecular level, characterized by transcriptomic and epigenetic alterations.1–3In ASD, upregulation of microglial, astrocyte, and immune signaling genes, downregulation of specific synaptic genes, and attenuation of regional gene expression differences are observed.1,2,4–6However, whether these changes are limited to the cortical association areas profiled is unknown. Here, we perform RNA-sequencing (RNA-seq) on 725 brain samples spanning 11 distinct cortical areas in 112 ASD cases and neurotypical controls. We identify substantially more genes and isoforms that differentiate ASD from controls than previously observed. These alterations are pervasive and cortex-wide, but vary in magnitude across regions, roughly showing an anterior to posterior gradient, with the strongest signal in visual cortex, followed by parietal cortex and the temporal lobe. We find a notable enrichment of ASD genetic risk variants among cortex-wide downregulated synaptic plasticity genes and upregulated protein folding gene isoforms. Finally, using snRNA-seq, we determine that regional variation in the magnitude of transcriptomic dysregulation reflects changes in cellular proportion and cell-type-specific gene expression, particularly impacting L3/4 excitatory neurons. These results highlight widespread, genetically-driven neuronal dysfunction as a major component of ASD pathology in the cerebral cortex, extending beyond association cortices to involve primary sensory regions.
A COMPARATIVE STUDY OF ANAESTHETIC AGENTS ON HIGH VOLTAGE ACTIVATED CALCIUM CHANNEL CURRENTS IN IDENTIFIED MOLLUSCAN NEURONS
Authors: Morris Terrence J. , Hopkins Philip M. , Winlow William 
Published: December 2020

SUMMARYUsing the two electrode voltage clamp configuration, a high voltage activated whole-cell Ca2+channel current (IBa) was recorded from a cluster of neurosecretory ‘Light Yellow’ Cells (LYC) in the right parietal ganglion of the pond snailLymnaea stagnalis.Recordings of IBafrom LYCs show a reversible concentration-dependent depression of current amplitude in the presence of the volatile anaesthetics halothane, isoflurane and sevoflurane, or the non-volatile anaesthetic pentobarbitone at clinical concentrations.In the presence of the anaesthetics investigated, IBameasured at the end of the depolarizing test pulse showed proportionally greater depression than that at measured peak amplitude, as well as significant decrease in the rate of activation or increase in inactivation or both.Within the range of concentrations used, the concentration-response plots for all the anaesthetics investigated correlate strongly to straight line functions, with linear regression R2values > 0.99 in all instances.For volatile anaesthetics, the dose-response regression slopes for IBaincrease in magnitude, in order of gradient: sevoflurane, isoflurane and halothane, a sequence which reflects their order of clinical potency in terms of MAC value.
Preventive training interferes with mRNA-encoding myosin 7 and collagen I expression during pulmonary arterial hypertension
Authors: Mariano Thaoan Bruno , de Souza Castilho Anthony César , Sabela Ana Karenina Dias de Almeida , de Oliveira André Casanova , Cury Sarah Santiloni , Aguiar Andreo Fernando , Dias Raisa de Jesus Dutra , Cicogna Antonio Carlos , Okoshi Katashi , Justulin Junior Luis Antonio , Carvalho Robson Francisco , Pacagnelli Francis Lopes 
Published: December 2020

AbstractTo gain insight on the impact of preventive exercise during pulmonary arterial hypertension (PAH), we evaluated the gene expression of myosins and gene-encoding proteins associated with the extracellular matrix remodeling of right hypertrophied ventricles. We used 32 male Wistar rats, separated in four groups: Sedentary Control (S; n=8); Control with Training (T; n=8); Sedentary with Pulmonary Arterial Hypertension (SPAH; n=8); and Pulmonary Arterial Hypertension with Training (TPAH; n=8). The rats trained for thirteen weeks on a treadmill. They had two weeks of adaptation training. The PAH was induced by application of monocrotaline 60 mg/kg. Consequential right ventricular dysfunction was observed after the 10th week of training. Rats in the control group received saline application. At the end of the 13th week, echocardiography analysis confirmed cardiac dysfunction. Collagen content and organization was assessed through picrosirius red staining and fractal dimension (FD) analysis, respectively. Transcript abundance was estimated through reverse transcription-quantitative PCR (RT-qPCR). Cardiac dysfunction was confirmed by the reduction in maximum pulmonary artery velocity and pulmonary artery acceleration time. Through histomorphometric assessment, we found no differences in the interstitial collagen FD between groups. Regarding gene expression,myh7gene expression was upregulated in the TPAH group. However, this did not occur with the S group. PAH also increased the mRNA abundance ofcol1a1in the SPAH and TPAH groups. Moreover, the TPAH group showed a higher abundance of this gene when compared to the S group. With these findings, we concluded that preventive exercise had a positive impact on compensated hypertrophy during pulmonary hypertension. This can be explained in part by the modulation of the extracellular matrix and myosin gene expression in trained rats.
Identification of Celastrol as a novel HIV-1 Latency Reversal Agent by an Image-Based Screen
Authors: Liu Hongbing , Hu Pei-Wen , Dubrulle Julien , Stossi Fabio , Nikolai Bryan C. , Mancini Michael A. , Rice Andrew P. 
Published: December 2020

AbstractAlthough current antiretroviral therapies (ART) are successful in controlling HIV-1 infection, a stable viral reservoir reactivates when ART is discontinued. Consequently, there is a major research effort to develop approaches to disrupt the latent viral reservoir and enhance the immune system’s ability to clear HIV-1. A number of small molecules, termed latency reversal agents (LRAs), have been identified which can reactivate latent HIV-1 in cell lines and patients’ cellsex vivo. However, clinical trials have suggested that combinations of LRAs will be required to efficiently reactivate HIV-1in vivo, especially LRAs that act synergistically by functioning through distinct pathways. To identify novel LRAs, we used an image-based assay to screen a natural compound library for the ability to induce a low level of aggregation of resting primary CD4+T cells from healthy donors. We identified celastrol as a novel LRA. Celastrol functions synergistically with other classes of LRA to reactivate latent HIV-1 in a Jurkat cell line, suggesting a novel mechanism in its LRA activity. Additionally, celastrol does not appear to activate resting CD4+T cells at levels at which it can reactivate latent HIV-1. Celastrol appears to represent a novel class of LRAs and it therefore can serve as a lead compound for LRA development.
Understanding Thioamitide Biosynthesis Using Pathway Engineering and Untargeted Metabolomics
Authors: Eyles Tom H. , Vior Natalia M. , Lacret Rodney , Truman Andrew W. 
Published: December 2020

ABSTRACTThiostreptamide S4 is a thioamitide, a family of promising antitumour ribosomally synthesised and post-translationally modified peptides (RiPPs). The thioamitides are one of the most structurally complex RiPP families, yet very few thioamitide biosynthetic steps have been elucidated, even though the gene clusters of multiple thioamitides have been identified. We hypothesised that engineering the thiostreptamide S4 gene cluster in a heterologous host could provide insights into its biosynthesis when coupled with untargeted metabolomics and targeted mutations of the precursor peptide. Modified gene clusters were constructed, and in-depth metabolomics enabled a detailed understanding of the biosynthetic pathway, including the identification of an effector-like protein critical for amino acid dehydration. We use this biosynthetic understanding to bioinformatically identify new widespread families of RiPP biosynthetic gene clusters, paving the way for future RiPP discovery and engineering.
Retrograde And Anterograde Transport Of LAT-Vesicles During The Immunological Synapse Formation: Defining The Finely-Tuned Mechanism
Authors: Saez Juan José , Dogniaux Stéphanie , Shafaq-Zadah Massiullah , Johannes Ludger , Hivroz Claire , Zucchetti Andrés Ernesto 
Published: December 2020

ABSTRACTLAT is an important player of the signaling cascade induced by TCR activation. This adapter molecule is present at the plasma membrane of T lymphocytes and more abundantly in intracellular compartments. Upon T-cell activation the intracellular pool of LAT is recruited to the immune synapse (IS). We previously described two pathways controlling LAT trafficking: retrograde transport from endosomes to the TGN, and anterograde traffic from the Golgi to the IS. We address the specific role of 4 proteins, the GTPase Rab6, the t-SNARE syntaxin-16, the v-SNARE VAMP7 and the golgin GMAP210, in each pathway. Using different methods (endocytosis and Golgi trap assays, confocal and TIRF microscopy, TCR-signalosome pull down) we show that syntaxin-16 is regulating the retrograde transport of LAT whereas VAMP7 is regulating the anterograde transport. Moreover, GMAP210 and Rab6, known to contribute in both pathways, are in our cellular context specifically and respectively involved in anterograde and retrograde transport of LAT. Altogether, our data describe how retrograde and anterograde pathways coordinate LAT enrichment at the IS and point the Golgi as a central hub for the polarized recruitment of LAT to the IS. The role that this finely-tuned transport of signaling molecules plays in T-cell activation is discussed.
Development and validation of a combined species SNP array for the European seabass (Dicentrarchus labrax) and gilthead seabream (Sparus aurata)
Authors: Peñaloza C. , Manousaki T. , Franch R. , Tsakogiannis A. , Sonesson A. , Aslam M. L. , Allal F. , Bargelloni L. , Houston R. D. , Tsigenopoulos C. S. 
Published: December 2020

AbstractSNP arrays are powerful tools for high-resolution studies of the genetic basis of complex traits, facilitating both population genomic and selective breeding research. The European seabass (Dicentrarchus labrax) and the gilthead seabream (Sparus aurata) are the two most important fish species for Mediterranean aquaculture. While selective breeding programmes increasingly underpin stocky supply for this industry, genomic selection is not yet widespread. Genomic selection has major potential to expedite genetic gain, in particular for traits practically impossible to measure on selection candidates, such as disease resistance and fillet yield. The aim of our study was to design a combined-species 60K SNP array for both European seabass and gilthead seabream, and to validate its performance on farmed and wild populations from numerous locations throughout the species range. To achieve this, high coverage Illumina whole genome sequencing of pooled samples was performed for 24 populations of European seabass and 27 populations of gilthead seabream. This resulted in a database of ~20 million SNPs per species, which were then filtered to identify high-quality variants and create the final set for the development of the ‘MedFish’ SNP array. The array was then tested by genotyping a subset of the discovery populations and demonstrated a high conversion rate to functioning polymorphic assays on the array (92% in seabass: 89% in seabream) and repeatability (99.4 - 99.7%). The platform interrogates ~30K markers in each fish species, includes features such as SNPs previously shown to be associated with performance traits, and is enriched for SNPs predicted to alter protein function. The array was demonstrated to be effective at detecting population structure across a wide range of fish populations from diverse geographical origins, and to examine the extent of haplotype sharing among Mediterranean fish farms. Therefore, the MedFish array enables efficient and accurate high-throughput genotyping for genome-wide distributed SNPs on each fish species, and will facilitate stock management, population genomics approaches, and acceleration of selective breeding through genomic selection.
The evolution of social parasitism inFormicaants revealed by a global phylogeny
Authors: Borowiec Marek L. , Cover Stefan P. , Rabeling Christian 
Published: December 2020

AbstractStudying the behavioral and life history transitions from a cooperative, eusocial life history to exploitative social parasitism allows for deciphering the conditions under which changes in behavior and social organization lead to diversification. The Holarctic ant genusFormicais ideally suited for studying the evolution of social parasitism because half of its 176 species are confirmed or suspected social parasites, which includes all three major classes of social parasitism known in ants. However, the life-history transitions associated with the evolution of social parasitism in this genus are largely unexplored. To test competing hypotheses regarding the origins and evolution of social parasitism, we reconstructed the first global phylogeny ofFormicaants and representative formicine outgroups. The genusFormicaoriginated in the Old World during the Oligocene (∼30 Ma ago) and dispersed multiple times to the New World. WithinFormica, the capacity for dependent colony foundation and temporary social parasitism arose once from a facultatively polygynous, independently colony founding ancestor. Within this parasitic clade, dulotic social parasitism evolved once from a facultatively temporary parasitic ancestor that likely practiced colony budding frequently. Permanent social parasitism evolved twice from temporary social parasitic ancestors that rarely practiced colony budding, demonstrating that obligate social parasitism can originate from different facultative parasitic backgrounds in socially polymorphic organisms. In contrast to inquiline ant species in other genera, the high social parasite diversity inFormicalikely originated via allopatric speciation, highlighting the diversity of convergent evolutionary trajectories resulting in nearly identical parasitic life history syndromes.
Quantifying a Frequency Modulation Response Biomarker in Responsive Neurostimulation
Authors: Venkatesh Praveen , Sneider Daniel , Danish Mohammed , Sisterson Nathaniel D. , Zaher Naoir , Urban Alexandra , Grover Pulkit , Richardson R. Mark , Kokkinos Vasileios 
Published: December 2020

AbstractObjectiveResponsive Neurostimulation (RNS) is an effective treatment for controlling seizures in patients with drug-resistant focal epilepsy who are not suitable candidates for resection surgery. A lack of tools for detecting and characterizing potential response biomarkers, however, contributes to a limited understanding of mechanisms by which RNS improves seizure control. We developed a method to quantify ictal frequency modulation, previously identified as a biomarker of clinical responsiveness to RNS.ApproachFrequency modulation is characterized by shifts in power across spectral bands during ictal events, over several months of neurostimulation. This effect was quantified by partitioning each seizure pattern into segments with distinct spectral content and measuring the extent change from the baseline distribution of spectral content using the squared Earthmover’s distance.Main resultsWe analyzed intracranial electroencephalography data from 13 patients who received RNS therapy, six of whom exhibited frequency modulation on expert evaluation. Subjects in the frequency modulation group had, on average, significantly larger and more sustained changes in their Earthmover’s distances (mean = 13.97×10-3± 1.197×10-3). In contrast, those subjects without expert-identified frequency modulation exhibited statistically insignificant or negligible distances (mean = 4.994×10-3± 0.732×10-3).SignificanceThis method is the first step towards a quantitative, feedback-driven system for systematically optimizing RNS stimulation parameters, with an ultimate goal of truly personalized closed-loop therapy for epilepsy.