bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host Induced Gene Silencing of theSclerotinia sclerotiorum ABHYDROLASE-3gene reduces disease severity inBrassica napus
Authors: Wytinck Nick , Ziegler Dylan J. , Walker Philip L. , Sullivan Daniel S. , Biggar Kirsten T. , Khan Deirdre , Sakariyahu Solihu K. , Wilkins Olivia , Whyard Steve , Belmonte Mark F. 
Published: November 2021

AbstractSclerotinia sclerotiorumis a pathogenic fungus that infects hundreds of crop species, causing extensive yield loss every year. Chemical fungicides are used to control this phytopathogen, but with concerns about increasing resistance and impacts on non-target species, there is a need to develop alternative control measures. In the present study, we engineeredBrassica napusto constitutively express a hairpin (hp)RNA molecule to silenceABHYRDOLASE-3inS. sclerotiorum. We demonstrate the potential for Host Induced Gene Silencing (HIGS) to protectB. napusfromS. sclerotiorumusing leaf, stem and whole plant infection assays. The interaction between the transgenic host plant and invading pathogen was further characterized at the molecular level using dual-RNA sequencing and at the anatomical level through microscopy to understand the processes and possible mechanisms leading to increased tolerance to this damaging necrotroph. We observed significant shifts in the expression of genes relating to plant defense as well as cellular differences in the form of structural barriers around the site of infection in the HIGS-protected plants. Our results provide proof-of-concept that HIGS is an effective means of limiting damage caused byS. sclerotiorumto the plant and demonstrates the utility of this biotechnology in the development of resistance against fungal pathogens.
Fitness costs associated with spinetoram resistance inSpodoptera frugiperdais driven by host plants
Authors: Kanno Rubens H. , Guidolin Aline S. , Padovez Fernando E. O. , Rodrigues Juliana G. , Omoto Celso 
Published: November 2021

AbstractInsecticide resistance is usually associated with fitness costs. The magnitude of fitness costs is affected by environmental and ecological factors. Here, we explored how host plants could affect fitness costs associated with insecticide resistance. Initially, spinetoram-resistant (RR) and susceptible (SS) strains ofSpodoptera frugiperdawere selected using F2screen from a population collected in São Desidério, Bahia State, Brazil in 2018. Besides de RR and SS strains, fitness costs were also assessed for a heterozygous strain (RS). Life-history traits were evaluated to estimate population growth parameters of neonate larvae of each strain fed on corn, soybean and cotton plants. Compared to the SS strain, the relative fitness of the RR strain, based on intrinsic rate of population increase, was 1.06, 0.84 and 0.67 on plants of corn, soybean and cotton respectively. The relative fitness of the RS strain was similar to the SS strain regardless the host plant, suggesting a recessive fitness cost. No differences were found between the strains fed on corn plants. The larval development time was greater for RR strain fed on soybean and cotton plants compared to RS and SS strain. Low survival rate and fecundity of the RR strain were found when larvae fed on plants of soybean and cotton. The results of this study demonstrated that fitness costs of spinetoram resistance inS. frugiperdadepend strongly on the host plants thatS. frugiperdalarvae fed on. Such information can be used to design resistance management strategies considering the host plants of the agricultural landscape.Key messagesThe presence of fitness costs associated with resistance can be exploited in resistance management strategies.Host plant influences the fitness costs associated with spinetoram resistance inS. frugiperda.Information considering the host plants in an agricultural landscape is essential to design effective resistance management programs.
Staphylococcus aureus β-toxin exerts anti-angiogenic effects by inhibiting re-endothelialization and neovessel formation
Authors: Tran Phuong M. , Tang Sharon S. , Salgado-Pabón Wilmara 
Published: November 2021

SUMMARYStaphylococcus aureus is the causative agent of numerous severe human infections associated with significant morbidity and mortality worldwide. S. aureus often targets the vascular endothelium to interfere with proper host responses during invasive infections. In this study, we provide evidence that S. aureus β-toxin inhibits wound repair mechanisms in human endothelial cells by preventing cell proliferation and migration. These findings were confirmed in a rabbit aortic explant model where β-toxin impedes sprout formation. Decreased cell proliferation was accompanied by decreased production of the angiogenic proteins endothelin-1, IGFBP-3, thrombospondin-1, TIMP-1, and TIMP-4. Meanwhile, inhibited wound repair was marked by increased HGF secretion from endothelial cells, likely a marker of endothelial cell damage. Together, these findings establish a mechanistic role for β-toxin where it inhibits proper tissue repair processes that likely promote S. aureus infective niche.
Noise in a metabolic pathway leads to persister formation in Mycobacterium tuberculosis
Authors: Quigley Jeffrey , Lewis Kim 
Published: November 2021

AbstractTuberculosis is difficult to treat due to dormant cells in hypoxic granulomas, and stochastically-formed persisters tolerant of antibiotics. Bactericidal antibiotics kill by corrupting their energy-dependent targets. We reasoned that noise in the expression of an energy-generating component will produce rare persister cells. In sorted low ATP M. tuberculosis grown on acetate there is considerable cell-to-cell variation in the level of mRNA coding for AckA, the acetate kinase. Quenching the noise by overexpressing ackA sharply decreases persisters, showing that it acts as the main persister gene under these conditions. This demonstrates that a low energy mechanism is responsible for the formation of M. tuberculosis persisters and suggests that the mechanism of their antibiotic tolerance is similar to that of dormant cells in a granuloma. Entrance into a low energy state driven by stochastic variation in expression of energy-producing enzymes is likely a general mechanism by which bacteria produce persisters.
Inhibitory co-transmission from midbrain dopamine neurons relies on presynaptic GABA uptake
Authors: Melani Riccardo , Tritsch Nicolas X. 
Published: November 2021

ABSTRACTDopamine (DA)-releasing neurons in the substantia nigra pars compacta (SNcDA) inhibit target cells in the striatum through postsynaptic activation of γ-aminobutyric acid (GABA) receptors. However, the molecular mechanisms responsible for GABAergic signaling remain unclear, as SNcDA neurons lack enzymes typically required to produce GABA or package it into synaptic vesicles. Here we show that aldehyde dehydrogenase 1a1 (Aldh1a1), an enzyme proposed to function as a GABA synthetic enzyme in SNcDA neurons does not produce GABA for synaptic transmission. Instead, we demonstrate that SNcDA axons obtain GABA exclusively through presynaptic uptake using the membrane GABA transporter Gat1 (encoded by Slc6a1). GABA is then packaged for vesicular release using the vesicular monoamine transporter Vmat2. Our data therefore show that presynaptic transmitter recycling can substitute for de novo GABA synthesis and that Vmat2 contributes to vesicular GABA transport, expanding the range of molecular mechanisms available to neurons to support inhibitory synaptic communication.
HiCArch: A Deep Learning-based Hi-C Data Predictor
Authors: Zheng Xiao , Wang Jinghua , Wang Chaochen 
Published: November 2021

AbstractHi-C sequencing analysis is one of the most popular methods to study three-dimensional (3D) genome structures, which affect the gene expression and other cellular activities by allowing distal regulations in spatial proximity. Hi-C sequencing analysis enhances understanding of chromatin functionality. However, due to the high cost of Hi-C sequencing, the publicly available Hi-C data of high resolutions (such as 10kb) are limited in only a few cell types. In this paper we present HiCArch, a light-weight deep neural network that predicts Hi-C contact matrices from 11 common 1D epigenomic features. HiCArch identifies topological associated domains (TADs) of 10kb resolution within the distance of 10Mb. HiCArch obtains train Pearson correlation score at 0.9123 and test Pearson correlation score at 0.9195 when trained on K562 cell line. which are significantly higher than previous approaches, such as HiC-Reg[1], Akita[2], DeepC[3], and Epiphany[4].
Intralocus sexual conflict can maintain alternative reproductive tactics
Authors: Gamble Madilyn Marisa , Calsbeek Ryan G 
Published: November 2021

AbstractAlternative reproductive tactics (ARTs) are ubiquitous throughout the animal kingdom. Multiple mechanisms have been proposed to explain the maintenance of ARTs over time, including disruptive and negative frequency-dependent selection and female choice. However, these mechanisms focus exclusively on selection in the sex exhibiting the polymorphism, potentially limiting our understanding of the evolutionary causes and consequences of ARTs. Here we explore the role that intralocus sexual conflict may play in the maintenance of sex-specific ARTs. We use a genetically explicit individual-based model in which female fecundity and male tactic share a genetic architecture. By modeling ART maintenance under varying selection regimes and levels of sex-specific gene expression, we explore the conditions under which intralocus sexual conflict can maintain a hypothetical ART defined by two color morphs that depend on an underlying liability trait. Our models consistently revealed that sexual conflict can result in the persistence of a sex-specific polymorphism over hundreds of generations, even in the absence of negative frequency-dependent selection. ARTs were maintained through correlated selection when one male ART has lower fitness but produces daughters with higher fitness. Importantly, the maintenance of ARTs through sexual conflict resulted in a significant reduction in population growth rate, indicating that the evolutionary mechanism of ART maintenance can have broad ecological consequences. These results highlight the importance of understanding selection on both sexes when attempting to explain the maintenance of ARTs. Our results are consistent with a growing literature documenting genetic correlations between male ARTs and female fitness, suggesting that the maintenance of sex-specific ARTs through intralocus sexual conflict may be common and widespread in nature.
Synaptic Activity-Dependent Changes in the Hippocampal Palmitoylome
Authors: Nasseri Glory , Matin Nusrat , Tosefsky Kira , Stacey Greg , Flibotte Stephane , Hollman Rocio , Wild Angela R. , Foster Leonard J. , Bamji Shernaz X. 
Published: November 2021

ABSTRACTDynamic protein S-palmitoylation is critical for neuronal function, development, and synaptic plasticity. Activity-dependent changes in palmitoylation have been observed for several neuronal substrates, however a full characterization of the activity-regulated palmitoylome is lacking. Here, we use an unbiased approach to identify differentially palmitoylated proteins in the mouse hippocampus following context-dependent fear conditioning. Of the 121 differentially palmitoylated proteins identified 63 were synaptic proteins, while others were associated with metabolic functions, cytoskeletal organization, and signal transduction. The vast majority of synaptic proteins exhibited increased palmitoylation following fear conditioning, whereas proteins that exhibited decreased palmitoylation were predominantly associated with metabolic processes. We show a link between dynamic palmitoylation and synapse plasticity by demonstrating that the palmitoylation of one of our identified proteins, PRG-1/LPPR4, is essential for activity-induced insertion of AMPA receptors into the postsynaptic membrane. Together, this study identifies networks of synaptic proteins whose dynamic palmitoylation may play a central role in learning and memory.SUMMARYThis study identifies networks of proteins that undergo dynamic post-translational palmitoylation in response to fear conditioning and demonstrates that palmitoylation of one of these proteins is essential for synapse plasticity. Together, this illustrates the importance of palmitoylation in learning/memory and synapse plasticity.
Identifying Microbial Interaction Networks Based on Irregularly Spaced Longitudinal 16S rRNA sequence data
Authors: Zhou Jie , Gui Jiang , Viles Weston D. , Chen Haobin , Madan Juliette C. , Coker Modupe O. , Hoen Anne G. 
Published: November 2021

AbstractThe microbial interactions within the human microbiome are complex and temporally dynamic, but few methods are available to model this system within a longitudinal network framework. Based on general longitudinal 16S rRNA sequence data, we propose a stationary Gaussian graphical model (SGGM) for microbial interaction networks (MIN) which can accommodate the possible correlations between the high-dimensional observations. For SGGM, an EM-type algorithm is devised to compute theL1-penalized maximum likelihood estimate of MIN which employs the classic graphical LASSO algorithm as the building block and can therefore be implemented easily. Simulation studies show that the proposed algorithms can significantly outperform the conventional algorithms when the correlations between measurements grow large. The algorithms are then applied to a real 16S rRNA gene sequence data set for gut microbiome. With the estimated MIN in hand, module-preserving permutation test is proposed to test the independence of the MIN and the corresponding phylogenetic tree. The results demonstrate strong evidence of an association between the MIN and the phylogenetic tree which indicates that the genetically related taxa tend to have more/stronger interactions. The proposed algorithms are implemented in R packagelglassoathttps://CRAN.R-project.org/package=lglasso.
Phenotype-Centric Modeling for Rational Metabolic Engineering
Authors: Valderrama-Gómez Miguel Á. , Savageau Michael A. 
Published: November 2021

AbstractPhenotype-centric modeling enables a paradigm shift in the analysis of kinetic models. It brings the focus to a network’s biochemical phenotypes and their relationship with measurable traits (e.g., product yields, system dynamics, signal amplification factors, etc.) and away from computationally intensive parameter sampling and numerical simulation. Here, we explore applications of this new modeling strategy in the field of Rational Metabolic Engineering using the amorphadiene biosynthetic network as a case study. Our phenotype-centric approach not only identifies known beneficial intervention strategies for this network, but it also provides an understanding of mechanistic context for the validity of these predictions. Additionally, we propose a set of hypothetical strains with the potential to outperform reported production strains and enhance the mechanistic understanding of the amorphadiene biosynthetic network. We believe that phenotype-centric modeling can advance the field of Rational Metabolic Engineering by enabling the development of next generation kinetics-based algorithms and methods that do not rely ona prioriknowledge of kinetic parameters but allow a structured, global analysis of the design space of parameter values.
Life Strategies in Placozoa
Authors: Romanova Daria Y. , Nikitin Mikhail A. , Shchenkov Sergey V. , Moroz Leonid L. 
Published: November 2021

AbstractPlacozoans are essential reference species for understanding the origins and evolution of the animal organization. However, little is known about their life strategies in natural habitats. Here, by establishing long-term culturing for four species ofTrichoplaxandHoilungia, we extend our knowledge about feeding and reproductive adaptations relevant to their ecology and immune mechanisms. Three modes of population growth depended upon feeding sources, including induction of social behaviors and different reproductive strategies. In addition to fission, representatives of all haplotypes produced ‘swarmers,’ which could be formed from the lower epithelium (with greater cell- type diversity) as a separate asexual reproduction stage. In aging culture, we reported the formation of specialized structures (‘spheres’) from the upper cell layer as a part of the innate immune defense response with the involvement of fiber cells. Finally, we showed that regeneration could be a part of the adaptive reproductive strategies in placozoans and a unique model for regenerative biology in general.
A middle ground where executive control meets semantics: The neural substrates of semantic-control are topographically sandwiched between the multiple-demand and default-mode systems
Authors: Chiou Rocco , Jefferies Elizabeth , Duncan John , Humphreys Gina F. , Lambon Ralph Matthew A. 
Published: November 2021

AbstractSemantic control is the capability to operate on meaningful representations, selectively focusing on certain aspects of meaning while purposefully ignoring other aspects based on one’s behavioural aim. This ability is especially vital for comprehending figurative/ambiguous language. It remains unclear, at the topographical level, why/how regions involved in semantic control seem reliably juxtaposed alongside other functionally specialised regions in the association cortex. We investigated this issue by characterising how semantic control regions topographically relate to the default-mode network (associated with memory and abstract cognition) and multiple-demand network (associated with executive control). Topographically, we confirmed that semantic control areas were sandwiched by the default-mode and multi-demand networks, forming an orderly arrangement observed both at the individual- and group-level. Functionally, semantic control regions exhibited ‘hybrid’ responses, fusing a preference for cognitively demanding processing (multiple-demand) and a preference for meaningful representations (default-mode) into a domain-specific preference for difficult operations on meaningful representations. When projected onto the principal gradient of human connectome, the neural activity of semantic control showed a robustly dissociable trajectory from visuospatial control, implying different roles in the functional transition from sensation to cognition. We discuss why the hybrid functional profile of semantic control regions might result from their intermediate topographical positions.
Experimental analysis and biaxial biomechanical behaviour of ex-vivo sheep trachea
Authors: Nemavhola Fulufhelo , Ngwangwa Harry , Pandelani Thanyani 
Published: November 2021

AbstractPurposeThe purpose of this study is to investigate the mechanical behaviour of the tracheal tissue under biaxial tensile loading. Furthermore, the study examines the material properties of the tissue through a study of the model parameters for six constitutive models.Materials and methodsThe fourteen (n = 13) trachea sheep (Vleis Merino) pieces of tissues measured to be ~ 30 × 20 mm where only the effective area subjected to engineering strain was ~ 25 × 16 mm. In this study, we assume that the tracheal tissue is anisotropic and incompressible, therefore we apply and study the material parameters from six models namely the Fung, Choi-Vito, Holzapfel (2000), Holzapfel (2005), Polynomial (Anisotropic) and Four-Fiber Family models.ResultsThe results show that the trachea tissue is twice as stiff along the circumferential direction as it is along the longitudinal direction. It is also observed that the material properties are different (non-homogeneous) along the trachea.ConclusionsThe findings of this study will benefit computational models for the study of tracheal diseases or injuries. Furthermore, these findings will assist in the development of regenerative medicine for different tracheal pathologies and in the bioengineering of replacement tissue in cases of damage.
A chemical-genetic map of the pathways controlling drug potency in Mycobacterium tuberculosis
Authors: Li Shuqi , Poulton Nicholas C. , Chang Jesseon S. , Azadian Zachary A. , DeJesus Michael A. , Ruecker Nadine , Zimmerman Matthew D. , Eckartt Kathryn , Bosch Barbara , Engelhart Curtis , Sullivan Daniel , Gengenbacher Martin , Dartois Véronique A. , Schnappinger Dirk , Rock Jeremy M. 
Published: November 2021

ABSTRACTMycobacterium tuberculosis (Mtb) infection is notoriously difficult to treat. Treatment efficacy is limited by Mtb’s intrinsic drug resistance, as well as its ability to evolve acquired resistance to all antituberculars in clinical use. A deeper understanding of the bacterial pathways that govern drug efficacy could facilitate the development of more effective therapies to overcome resistance, identify new mechanisms of acquired resistance, and reveal overlooked therapeutic opportunities. To define these pathways, we developed a CRISPR interference chemical-genetics platform to titrate the expression of Mtb genes and quantify bacterial fitness in the presence of different drugs. Mining this dataset, we discovered diverse and novel mechanisms of intrinsic drug resistance, unveiling hundreds of potential targets for synergistic drug combinations. Combining chemical-genetics with comparative genomics of Mtb clinical isolates, we further identified numerous new potential mechanisms of acquired drug resistance, one of which is associated with the emergence of a multidrug-resistant tuberculosis (TB) outbreak in South America. Lastly, we make the unexpected discovery of an “acquired drug sensitivity.” We found that the intrinsic resistance factor whiB7 was inactivated in an entire Mtb sublineage endemic to Southeast Asia, presenting an opportunity to potentially repurpose the macrolide antibiotic clarithromycin to treat TB. This chemical-genetic map provides a rich resource to understand drug efficacy in Mtb and guide future TB drug development and treatment.
α-Helix stabilization by co-operative side chain charge-reinforced interactions to phosphoserine in a basic kinase-substrate motif
Authors: Batchelor Matthew , Dawber Robert S. , Wilson Andrew J. , Bayliss Richard 
Published: November 2021

AbstractHow cellular functions are regulated through protein phosphorylation events that promote or inhibit protein–protein interactions (PPIs) is key to understanding regulatory molecular mechanisms. Whilst phosphorylation can orthosterically or allosterically influence protein recognition, phospho-driven changes in the conformation of recognition motifs are less well explored. We recently discovered that clathrin heavy chain recognises phosphorylated TACC3 through a helical motif that, in the unphosphorylated protein, is disordered. However, it was unclear whether and how phosphorylation could stabilize a helix in a broader context. In the current manuscript, we address this challenge using poly-Ala based model peptides and a suite of circular dichroism and nuclear magnetic resonance spectroscopies. We show that phosphorylation of a Ser residue stabilizes the α-helix in the context of an Arg(i – 3)pSeri Lys(i + 4) triad through charge-reinforced side chain interactions with positive co-operativity, whilst phosphorylation of Thr induces an opposing response. This is significant as it may represent a general method for control of PPIs by phosphorylation; basic kinase-substrate motifs are common with 55 human protein kinases recognising an Arg at a position –3 from the phosphorylated Ser, whilst the Arg(i – 3)pSeri Lys(i + 4) is a motif found in over 2000 human proteins.