bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of the Bacillus thuringiensis vip3A insecticidal toxin gene is activated at the onset of stationary phase by VipR, an autoregulated transcription factor
Authors: Chen Haibo , Verplaetse Emilie , Slamti Leyla , Lereclus Didier 
Published: May 2022

AbstractThe Vegetative insecticidal protein Vip3A is produced by some Bacillus thuringiensis strains from the mid-log growth phase to sporulation. Although Vip3A is important for the entomopathogenicity of B. thuringiensis, the vip3A gene regulation is unknown. In the B. thuringiensis kurstaki HD1 strain, vip3A is carried by the pBMB299 plasmid, which is absent in the closely related strain B. thuringiensis kurstaki HD73. Using a transcriptional fusion between the vip3A promoter and lacZ, we observed that the HD73 strain is unable to express vip3A. This result suggests that a specific regulator is required for vip3A expression. Assuming that the regulator gene is located on the same plasmid as vip3A, we transferred the pBMB299 from the HD1 strain to the HD73 strain. We found that Vip3A was produced in the HD73 strain containing pBMB299, suggesting that the regulator gene is located on this plasmid. Using this heterologous host and promoter-lacZ transcription fusions, we confirmed that VipR is essential to activate vip3A expression at the onset of stationary phase. We demonstrated that vipR transcription is positively autoregulated and the determination of the vipR and vip3A promoters pinpointed a putative VipR target upstream from the Sigma A-specific −10 region of these two promoters. Surprisingly, this conserved sequence was also found upstream of cry1I and cry2 genes. Finally, we showed that vip3A and vipR expression is drastically increased in a Δspo0A mutant unable to initiate sporulation. In conclusion, we have characterized a novel regulator involved in the entomopathogenic potency of B. thuringiensis through a sporulation-independent pathway.ImportanceThe insecticidal properties of Bacillus thuringiensis are mainly due to Cry toxins which form a crystalline inclusion during sporulation. However, other proteins participate in the pathogenicity of the bacterium, notably the Vip3A toxins that are produced from vegetative growth to sporulation. The VipR regulator that activates vip3A gene expression at the onset of stationary phase is positively autoregulated and analysis of the promoter region of the vip3A and vipR genes reveals the presence of a highly conserved DNA sequence. This possible VipR target sequence is also found upstream of the cry2A and cry1I genes, suggesting that Cry toxins can be produced before the bacteria enter sporulation. Such a result could allow us to better understand the role of Cry and Vip3A toxins during the B. thuringiensis infectious cycle in insects, in addition to the primary role of the Cry toxins in the toxemia caused by ingestion of crystals.
Cryo-tomography reveals rigid-body motion and organization of apicomplexan invasion machinery
Authors: Gui Long , O’Shaughnessy William J. , Cai Kai , Reetz Evan , Reese Michael L. , Nicastro Daniela 
Published: May 2022

AbstractThe apical complex is a specialized collection of cytoskeletal and secretory machinery in apicomplexan parasites, which include the pathogens that cause malaria and toxoplasmosis. Its structure and mechanism of motion are poorly understood. We used cryo-FIB-milling and cryo-electron tomography to visualize the 3D-structure of the apical complex in its protruded and retracted states. Averages of conoid-fibers revealed their polarity and unusual nine-protofilament arrangement with associated proteins connecting and likely stabilizing the fibers. Neither the structure of the conoidfibers nor the architecture of the spiral-shaped conoid complex change during protrusion or retraction. Thus, the conoid moves as a rigid body, and is not spring-like and compressible, as previously suggested. Instead, the apical-polar-rings (APR), previously considered rigid, dilate during conoid protrusion. We identified actin-like filaments connecting the conoid and APR during protrusion, suggesting a role during conoid movements. Furthermore, our data capture the parasites in the act of secretion during conoid protrusion.
A comparison of ImageJ and machine learning based image analysis methods to measure cassava bacterial blight disease severity
Authors: Elliott Kiona , Berry Jeffrey C. , Kim Hobin , Bart Rebecca S. 
Published: May 2022

AbstractBackgroundMethods to accurately quantify disease severity are fundamental to plant pathogen interaction studies. Commonly used methods include visual scoring of disease symptoms, tracking pathogen growth in planta over time, and various assays that detect plant defense responses. Several image-based methods for phenotyping of plant disease symptoms have also been developed. Each of these methods has different advantages and limitations which should be carefully considered when choosing an approach and interpreting the results.ResultsIn this paper, we developed two image analysis methods and tested their ability to quantify different aspects of disease lesions in the cassava-Xanthomonas pathosystem. The first method uses ImageJ, an open-source platform widely used in the biological sciences. The second method is a few-shot support vector machine learning tool that uses a classifier file trained with five representative infected leaf images for lesion recognition. Cassava leaves were syringe infiltrated with wildtype Xanthomonas, a Xanthomonas mutant with decreased virulence, and mock treatments. Digital images of infected leaves were captured overtime using a Raspberry Pi camera. The image analysis methods were analyzed and compared for the ability to segment the lesion from the background and accurately capture and measure differences between the treatment types.ConclusionsBoth image analysis methods presented in this paper allow for accurate segmentation of disease lesions from the non-infected plant. Specifically, at 4-, 6-, and 9-days post inoculation (DPI), both methods provided quantitative differences in disease symptoms between different treatment types. Thus, either method could be applied to extract information about disease severity. Strengths and weaknesses of each approach are discussed.
FebRNA: an automated fragment-ensemble-based model for building RNA 3D structures
Authors: Zhou Li , Wang Xunxun , Yu Shixiong , Tan Ya-Lan , Tan Zhi-Jie 
Published: May 2022

AbstractKnowledge of RNA 3-dimensional (3D) structures is critical to understanding the important biological functions of RNAs. Although various structure prediction models have been developed, high accuracy of predicted RNA 3D structures is still limited to the RNAs with short length or with simple topology. In this work, we proposed a new model, namely FebRNA, for building RNA 3D structures through fragment assembly based on coarse-grained (CG) fragment ensembles. Specifically, FebRNA is composed of four processes: establishing the library of different types of CG fragment ensembles, building CG 3D structure ensemble through fragment assembly, identifying top-1 CG structure through a CG scoring function, and rebuilding the all-atom structure from the top-1 CG one. Extensive examination on different types of RNA structures indicates that FebRNA gives consistently reliable predictions on RNA 3D structures including pseudoknots, 3-way junction, 4-way and 5-way junctions, and RNAs in the RNA-Puzzles. FebRNA is available at website: https://github.com/Tan-group/FebRNA.
Transcranial Direct Current Stimulation Alters the Waveform Shape of Cortical Gamma Oscillations
Authors: Marshall Tom R. , Quinn Andrew J. , Jensen Ole , Bergmann Til Ole 
Published: May 2022

AbstractNeuronal oscillations in different frequency bands have been linked to a wide variety of cognitive functions, and may even be a fundamental mechanism of inter-regional communication. For this reason, manipulation of oscillatory activity via brain stimulation is a central goal in neuroscience research. However, the vast majority of studies characterise oscillatory activity solely in terms of amplitude and frequency. Oscillations can also be characterised by their waveform shape; the degree to which they resemble or deviate from sinusoids. Here we exploit Empirical Mode Decomposition (EMD), a novel method that allows quantification of oscillatory waveform shape. We show for the first time that transcranial direct current stimulation (tDCS) alters the waveform shape of gamma oscillatory activity in the visual cortex. Notably, changes in waveform shape were limited to one half of the phase cycle; anodal stimulation led to a relatively slower, and cathodal to a relatively faster, descending half-wave. tDCS is generally believed to affect cortical excitability via alteration of resting membrane potential. Interestingly, simulations of altered cortical excitability in a gamma-generating neuronal population indicated the waveform shape changes observed experimentally likely stem from stimulation of pyramidal neurons. These findings have implications for understanding the neural consequences of tDCS at the level of neuronal population phenomena such as cortical oscillations and underscore the importance of waveform shape as an important feature of neuronal oscillations.
Human Cytomegalovirus induces neuronal enolase to support virally-mediated metabolic remodeling
Authors: Moreno Isreal , Rodríguez-Sánchez Irene , Schafer Xenia , Munger Joshua 
Published: May 2022

AbstractViruses depend on cellular metabolic resources to supply the energy and biomolecular building blocks necessary for their replication. Human Cytomegalovirus (HCMV), a leading cause of birth defects and morbidity in immunosuppressed individuals, induces numerous metabolic activities that are important for productive infection. However, many of the mechanisms through which these metabolic activities are induced and how they contribute to infection are unclear. We find that HCMV infection of fibroblasts induces a neuronal gene signature, as well as the expression of several metabolic enzyme isoforms that are typically expressed in other tissue types. Of these, the most substantially induced gene was the neuron-specific isoform of enolase (ENO2). Induction of ENO2 expression is important for HCMV-mediated glycolytic activation, as well as for the virally-induced remodeling of pyrimidine-sugar metabolism, which provides the glycosyl subunits necessary for protein glycosylation. Inhibition of ENO2 expression or activity reduced UDP-sugar pools, attenuated the accumulation of viral glycoproteins, and induced the accumulation of non-infectious viral particles. In addition, our data indicate that the induction of ENO2 expression depends on the HCMV UL38 protein. Collectively, our data indicate that HCMV infection induces a tissue atypical neuronal glycolytic enzyme to activate glycolysis and UDP-sugar metabolism to provide the glycosyl building blocks necessary for viral protein glycosylation and the production of infectious virions.Significance StatementViruses are obligate parasites that obtain energy and mass from their host cell. Control over the metabolic resources of the cell has emerged as an important host-pathogen interaction that can determine infectious outcomes. We find that the Human Cytomegalovirus (HCMV), a major cause of birth defects and morbidity in immunosuppressed patient populations, induces a neuronal gene signature in fibroblasts including the expression of neuronal-specific enolase (ENO2). Our data indicate that ENO2 is important for HCMV-mediated metabolic remodeling including glycolytic activation and the production of pyrimidine sugars, as well as for viral infectivity. These findings indicate that viruses are capable of tapping into alternative tissue-specific metabolic programs to support infection, highlighting an important viral mechanism of metabolic modulation.
Analysis of Aedes aegypti microRNAs in response to Wolbachia wAlbB infection and their potential role in mosquito longevity
Authors: Bishop Cameron , Hussain Mazhar , Hugo Leon E. , Asgari Sassan 
Published: May 2022

AbstractThe mosquito Aedes aegypti is the primary vector of a range of medically important viruses including dengue, Zika, West Nile, yellow fever, and chikungunya viruses. The endosymbiotic bacterium Wolbachia pipientis wAlbB strain is a promising biocontrol agent for blocking viral transmission by Ae. aegypti. To predict the long-term efficacy of field applications, a thorough understanding of the interactions between symbiont, host, and pathogen is required. Wolbachia influence host physiology in a variety of ways including reproduction, immunity, metabolism, and longevity. MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that regulate gene expression in eukaryotes and viruses. A number of miRNAs are known to regulate biological processes in Drosophila and mosquitoes, including facilitating Wolbachia maintenance. We generated the first chromosomal map of Ae. aegypti miRNAs, and compared miRNA expression profiles between a wAlbB-transinfected Ae. aegypti mosquito line and a tetracycline cleared derivative, using deep small RNA-sequencing. We found limited modulation of miRNAs in response to wAlbB infection. Several miRNAs were modulated in response to age, some of which showed greater upregulation in wAlbB-infected mosquitos than in tetracycline cleared ones. By selectively inhibiting some differentially expressed miRNAs, we identified miR-2946-3p and miR-317-3p as effecting mosquito longevity.ImportanceWolbachia is an endosymbiotic bacterium found in about 65% of insect species. It is mostly known for reproductive manipulations of the host, and also blocking replication of positive sense RNA viruses. Transinfection of Wolbachia into Aedes aegypti mosquitoes, which transmit a variety of arboviruses, including dengue virus, has provided a novel biological approach in reducing transmission of arboviruses. To gain a better understanding of Wolbachia-mosquito interactions, we investigated the impact of Wolbachia on the microRNA profile of Ae. aegypti mosquitoes. We produced the first chromosome-level map of Ae. Aegypti miRNAs. We found modulation of microRNAs in mosquitoes due to age, with two miRNAs, 317-3p and 2946-3p, showing significant increase with age. Inhibition of 317-3p and 2946-3p led to reduced mosquito life span in wAlbB-infected mosquitoes. The outcomes provide insights into underlying molecular mechanisms involved in Wolbachia-host interactions.
Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s Disease
Authors: Shah Disha , Gsell Willy , Wahis Jérôme , Luckett Emma S. , Jamoulle Tarik , Vermaercke Ben , Preman Pranav , Moechars Daan , Hendrickx Véronique , Jaspers Tom , Craessaerts Katleen , Horré Katrien , Wolfs Leen , Fiers Mark , Holt Matthew , Thal Dietmar Rudolf , Callaerts-Vegh Zsuzsanna , D’Hooge Rudi , Vandenberghe Rik , Himmelreich Uwe , Bonin Vincent , De Strooper Bart 
Published: May 2022

AbstractDysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate neuronal activity in the healthy brain, but their involvement in early network hyperactivity in AD is unknown. We show increased FC in the human cingulate cortex, several years before amyloid deposition. We found the same early cingulate FC disruption and neuronal hyperactivity inAppNL-Fmice. Crucially, these network disruptions are accompanied by decreased astrocyte calcium signaling. Recovery of astroglial calcium activity normalizes neuronal hyperactivity and FC, as well as seizure susceptibility and day/night behavioral hyperactivity. In conclusion, we show for the first time that astrocytes mediate initial features of AD and drive clinically relevant phenotypes.
Regulation of human trophoblast gene expression by endogenous retroviruses
Authors: Frost Jennifer M. , Amante Samuele M. , Okae Hiroaki , Jones Eleri M. , Ashley Brogan , Lewis Rohan M. , Cleal Jane K. , Caley Matthew P. , Arima Takahiro , Maffucci Tania , Branco Miguel R. 
Published: May 2022

AbstractThe placenta is a fast-evolving organ with large morphological and histological differences across eutherians, but the genetic changes driving placental evolution have not been fully elucidated. Transposable elements, through their capacity to quickly generate genetic variation and affect host gene regulation, may have helped to define species-specific trophoblast gene expression programmes. Here, we assessed the contribution of transposable elements to human trophoblast gene expression as enhancers or promoters. Using epigenomic data from primary human trophoblast and trophoblast stem cell lines, we identified multiple endogenous retrovirus families with regulatory potential that lie close to genes with preferential expression in trophoblast. These largely primate-specific elements are associated with inter-species gene expression differences, and are bound by transcription factors with key roles in placental development. Using genetic editing we demonstrated that several elements act as transcriptional enhancers of important placental genes, such asCSF1RandPSG5. We also identified an LTR10A element that regulatesENGexpression, affecting secretion of soluble ENG, with potential implications for preeclampsia. Our data show that transposons have made important contributions to human trophoblast gene regulation, and suggest that their activity may affect pregnancy outcomes.
Fixational eye movements as active sensation for high visual acuity
Authors: Nghiem Trang-Anh E. , Dufour Oscar , Reiniger Jenny L. , Harmening Wolf M. , da Silveira Rava Azeredo 
Published: May 2022

Perception and action are inherently entangled: our world view is shaped by how we explore and navigate our environment through complex and variable self-motion. Even when fixating on a stable stimulus, our eyes undergo small, involuntary movements. Fixational eye movements (FEM) render a stable world jittery on our retinae, which contributes noise to neural coding. Yet, empirical evidence suggests that FEM help rather than harm human perception of fine detail. Here, we elucidate this paradox by uncovering under which conditions FEM improve or impair retinal coding and human acuity. We combine theory and experiment: model accuracy is directly compared to that of healthy human subjects in a visual acuity task. Acuity is modeled by applying an ideal Bayesian classifier to simulations of retinal spiking activity in the presence of FEM. In addition, empirical FEM are monitored using high-resolution eye-tracking by an adaptive optics scanning laser ophthalmoscope. While FEM introduce noise, they also effectively pre-process visual inputs to facilitate retinal information encoding. Based on an interplay of these mechanisms, our model predicts a relation between visual acuity, FEM amplitude, and single-trial stimulus size that quantitatively accounts for experimental observations and captures the beneficial effect of FEM. Moreover, we observe that human subjects’ FEM statistics vary with stimulus size, and our model suggests that changing eye motion amplitude, as the subjects indeed do, enhances acuity as compared to maintaining eye motion size constant. Overall, our findings indicate that perception benefits from action even at the fine and noise-dominated spatio-temporal scale of FEM.Significance StatementPerception is inherently active: we need to move our eyes to see the world around us. Yet our eyes also undergo tiny, unconscious movements that can blur out fine visual details. Paradoxically, previous work suggested that these small movements aid fine detail perception. Here, we investigate this paradox to uncover in which contexts small eye movements help or harm visual acuity. Comparing a model of retinal responses with recordings of human visual acuity, we elucidate the mechanisms by which and conditions in which small eye movements support fine detail discrimination. Our results also suggest that varying eye movement amplitude according to stimulus size enhances retinal coding, highlighting that perception is active even at the level of very fine eye movements.
Extensive diversity of RNA viruses in ticks revealed by metagenomics in northeastern China
Authors: Liu Ziyan , Li Liang , Xu Wenbo , Yuan Yongxu , Liang Xiaojie , Zhang Li , Wei Zhengkai , Sui Liyan , Zhao Yinghua , Cui Yanyan , Yin Qing , Li Dajun , Li Qianxue , Wei Feng , Hou Zhijun , Liu Quan , Wang Zedong 
Published: May 2022

ABSTRACTRecently, several emerging tick-borne viruses have been identified to be associated with human diseases in northeastern China. Here, we used metagenomics to investigate the virome diversity in Haemaphysalis japonica, H. conicinna, Dermacentor silvarum, and Ixodes persulcatus ticks in northeastern China. A total of 22 RNA viruses were identified and belonged to more eight viral families, including four each in Nairoviridae and Phenuiviridae, three each in Flaviviridae, Rhabdoviridae, and Solemoviridae, two in Chuviridae, and one each in Partitiviridae, Tombusviridae, and unclassified. Of them, eight viruses were novel species, belonging to Nairoviridae (Ji’an nairovirus and Yichun nairovirus), Phenuiviridae (Mudanjiang phlebovirus), Rhabdoviridae (Tahe rhabdovirus 1-3), Chuviridae (Yichun mivirus), and Tombusviridae (Yichun tombus-like virus), and five members were established human pathogens, including Alongshan virus, tick-borne encephalitis virus, Songling virus, Beiji nairovirus, and Nuomin virus. I. persulcatus ticks had significant higher viral species than those in H. japonica, H. concinna, and D. silvarum ticks. Significant differences in tick viromes were observed among Daxingan, Xiaoxingan and Changbai mountains. These findings showed an extensive diversity of RNA viruses in ticks in northeastern China, revealed potential public health threats from the emerging tick-borne viruses. Further studies are needed to explain the natural circulation and pathogenicity of these viruses.