bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fright and Fight: Role of predation and competition on mate search tactics of wild male zebrafish
Authors: Ghoshal Aditya , Bhat Anuradha 
Published: March 2020

AbstractMate search tactics and association preferences among organisms in natural habitats can be dynamic and are determined by inherent trait preferences as well as the cost-benefit trade-offs associated with each mating decision. Two of the prime factors regulating mating decisions are the presence of competing conspecifics and predatory threats, both of which have important fitness consequences for the individual. We studied the influence of these two factors separately in mate search tactics and association preferences among zebrafish males. Male zebrafish were presented with a choice of two patches, consisting of different number of females, of which one patch was also associated with a predatory threat. We found that males made a preferential choice for the patch with more number of females only when the numerical difference between choices are starkly different, irrespective of the predatory threat associated with the patch. This points towards the role of numerical cognition in assessing cost-benefit tradeoffs in male zebrafish. We also studied the association preference of males in a multi-choice setup, consisting of four separate mixed-sex groups of zebrafish varying in densities. Our results showed that while test males preferred to visit the male-biased patches more often, they spent more time near female-biased patches or patches with equal sex ratio patches indicating the role of complex interplay of social cues in determining the associative behavior of males to a patch. This study, thus, sheds further light on the interactive roles of social cues and cognitive abilities in mate association patterns in this species.
Age dependent trans-cellular propagation of human tau aggregates inDrosophiladisease models
Authors: Aqsa  , Sarkar Surajit 
Published: March 2020

AbstractTauopathies is a class of neurodegenerative disorders which involves the transformation of physiological tau into pathogenic tau. One of the prime causes reported to drive this conversion is tau hyperphosphorylation and the subsequent propagation of pathogenic protein aggregates across the nervous system. Although past attempts have been made to deduce the details of tau propagation, yet not much is known about its mechanism. A better understanding of this aspect of disease pathology can prove to be beneficial for the development of diagnostic and therapeutic approaches. In our work, we utilize the plethora of advantages procured byDrosophilato introduce a novelin-vivotauopathy propagation model. For the first time, we demonstrate that the human tau (h-tau) possesses an intrinsic property to spread trans-cellularly in the fly nervous system irrespective of the tau allele or the neuronal tissue type. Aggregate migration restricted by targeted down-regulation of a specific kinase, elucidates the role of hyper-phosphorylation in its movement. On the contrary to the previous models, the present system enables a rapid, convenient and robustin-vivostudy of tau migration pathology. Henceforth, the developed model would not only be immensely helpful in uncovering the mechanistic in-depths of tau propagation pathology but also aid in modifier and/or drug screening for amelioration of tauopathies.
Non-retroviral endogenous viral element limits cognate virus replication inAedes aegyptiovaries
Authors: Suzuki Yasutsugu , Baidaliuk Artem , Miesen Pascal , Frangeul Lionel , Crist Anna B. , Merkling Sarah H. , Fontaine Albin , Lequime Sebastian , Moltini-Conclois Isabelle , Blanc Hervé , van Rij Ronald P. , Lambrechts Louis , Saleh Maria-Carla 
Published: March 2020

SummaryEndogenous viral elements (EVEs) are viral sequences integrated in host genomes. A large number of non-retroviral EVEs was recently detected inAedesmosquito genomes, leading to the hypothesis that mosquito EVEs may control exogenous infections by closely related viruses. Here, we experimentally investigated the role of an EVE naturally found inAedes aegyptipopulations and derived from the widespread insect-specific virus, cell-fusing agent virus (CFAV). Using CRISPR/Cas9 genome editing, we created anAe. aegyptiline lacking the CFAV EVE. Absence of the EVE resulted in increased CFAV replication in ovaries, possibly modulating vertical transmission of the virus. Viral replication was controlled by targeting of viral RNA by EVE-derived piRNAs. Our results provide evidence that antiviral piRNAs are produced in the presence of a naturally occurring EVE and its cognate virus, demonstrating a functional link between non-retroviral EVEs and antiviral immunity in a natural insect-virus interaction.
Presence of concurrent sarcoid-like granulomas indicate better survival in cancer patients
Authors: Murthi Mukunthan , Yoshioka Keiichiro , Cho Jeong Hee , Arias Sixto , Danna Elio , Holt Greg , Tatsumi Koichiro , Kawasaki Takeshi , Mirsaeidi Mehdi 
Published: March 2020

AbstractIntroductionAn increased risk of sarcoidosis and sarcoid-like reactions in subjects with a history of malignancy has been suggested. We assessed the incidence and clinical characteristics of cancer patients with biopsies containing sarcoid-like granulomas on cancer metastasis and patient survival.MethodsThis is a retrospective, multicenter, observational study involving patients who underwent Endobronchial Ultrasound (EBUS) at the University of Miami Hospital, Miami Veterans Affairs Medical Center in the USA and Chiba University in Japan. Subjects with a confirmed diagnosis of cancer and who subsequently developed granulomas in different organs were enrolled. The study was registered at Clinicaltrial.gov (NCT03844698).ResultsOne hundred and thirty-three patients met the study’s criteria. The most common primary cancer sites were the skin (22.5%), breast (20.3%), and lymph node (LN) (12.8%). Twenty-four (18%) patients developed sarcoidal granulomas within 1 year of cancer diagnosis, 54(40.6%) between 1 and 5 years and 49(36.8%) after 5 years. Imaging showed possible sarcoidal granulomas in lymph nodes in 51 cases (38.3%) and lung tissue and mediastinal lymph nodes in 73 cases (54.9%); some parenchymal reticular opacity and fibrosis were found in 5(3.7%) and significant parenchymal fibrosis in 2(1.5%) subjects. According to logistic regression analysis, the frequency of metastatic cancer was significantly lower in patients with sarcoidal granulomas than in controls. Moreover, multivariate Cox proportional hazard analysis showed a significant survival advantage in those with sarcoidal granuloma.ConclusionSarcoidal granulomas are uncommon pathology findings in cancer patients. There is a significant association between the presence of granulomas and reduced metastasis and increased survival. Further study is warranted to understand the protective mechanism involved.Take home messageOur findings suggest that patients with underlying malignancy who develop sarcoidosis and sarcoid-like reactions have a lower risk of stage 4 metastatic disease and better survival compared to patients who do not develop such granulomatous reactions.
Genetically encoded live cell sensor for tyrosinated microtubules
Authors: Kesarwani Shubham , Lama Prakash , Chandra Anchal , Reddy P. Purushotam , Jijumon AS , Bodakuntla Satish , Rao Balaji M , Janke Carsten , Das Ranabir , Sirajuddin Minhajuddin 
Published: March 2020

AbstractMicrotubule cytoskeleton exists in various biochemical forms in different cells due to tubulin post-translational modification (PTMs). These PTMs are known to affect microtubule stability, dynamics and interaction with MAPs and motors in a specific manner, widely known as tubulin code hypothesis. At present there exist no tool that can specifically mark tubulin PTMs in live cells, thus severely limiting our understanding of tubulin PTMs. Using yeast display library, we identified a binder against terminal tyrosine of alpha tubulin, a unique PTM site. Extensive characterization validates the robustness and non-perturbing nature of our binder as tyrosination sensor, a live cell tubulin nanobody specific towards tyrosinated or unmodified microtubules. Using which, in real time we followed nocodazole, colchicine and vincristine induced depolymerization events of unmodified microtubules, and found each distinctly perturb microtubule polymer. Together, our work describes the tyrosination sensor and potential applications to study microtubule and PTM processes in living cells.
Vesicular Trafficking Permits Evasion of cGAS/STING Surveillance During Initial Human Papillomavirus Infection
Authors: Uhlorn Brittany L. , Jackson Robert , Bratton Shauna M. , Li Shuaizhi , Van Doorslaer Koenraad , Campos Samuel K. 
Published: March 2020

AbstractOncogenic human papillomaviruses (HPVs) replicate in differentiating epithelium, causing 5% of cancers worldwide. Like most other DNA viruses, HPV infection initiates after trafficking viral genome (vDNA) to host cell nuclei. Cells possess innate surveillance pathways to detect microbial components or physiological stresses often associated with microbial infections. One of these pathways, cGAS/STING, induces IRF3-dependent antiviral interferon (IFN) responses upon detection of cytosolic DNA. Virion-associated vDNA can activate cGAS/STING during initial viral entry and uncoating/trafficking, and thus cGAS/STING is an obstacle to many DNA viruses. HPV has a unique vesicular trafficking pathway compared to many other DNA viruses. As the capsid uncoats within acidic endosomal compartments, minor capsid protein L2 protrudes across vesicular membranes to facilitate transport of vDNA to the Golgi. L2/vDNA resides within the Golgi lumen until G2/M, whereupon vesicular L2/vDNA traffics along spindle microtubules, tethering to chromosomes to access daughter cell nuclei. L2/vDNA-containing vesicles likely remain intact until G1, following nuclear envelope reformation. We hypothesize that this unique vesicular trafficking protects HPV from cGAS/STING surveillance. Here, we investigate cGAS/STING responses to HPV infection. DNA transfection resulted in acute cGAS/STING activation and downstream IFN responses. In contrast, HPV infection elicited minimal cGAS/STING and IFN responses. To determine the role of vesicular trafficking in cGAS/STING evasion, we forced premature viral penetration of vesicular membranes with membrane-perturbing cationic lipids. Such treatment renders a non-infectious trafficking-defective mutant HPV infectious, yet susceptible to cGAS/STING detection. Overall, HPV evades cGAS/STING by its unique subcellular trafficking, a property that may contribute to establishment of infection.ImportancePersistent infection is the main risk factor for all HPV-associated cancers. However, cellular innate immune pathways exist to detect and limit viral infections. The cGAS/STING pathway senses cytosolic DNA to initiate antiviral IFN responses. Such responses would likely be detrimental towards the establishment of persistent HPV infections. We therefore hypothesize that HPV evades cGAS/STING detection via its unique vesicular trafficking mechanism. Here, we show that indeed HPV is a stealthy virus, capable of infecting keratinocytes with minimal activation of the cGAS/STING pathway. Such evasion is dependent on HPV’s vesicular trafficking, as perturbation of vesicular integrity during infection results in sensing of virions.
Input dependent modulation of olfactory bulb activity by GABAergic basal forebrain projections
Authors: Böhm Erik , Brunert Daniela , Rothermel Markus 
Published: March 2020

AbstractBasal forebrain modulation of central circuits is associated with active sensation, attention and learning. While cholinergic modulations have been studied extensively the effect of non-cholinergic basal forebrain subpopulations on sensory processing remains largely unclear. Here, we directly compare optogenetic manipulation effects of two major basal forebrain subpopulations on principal neuron activity in an early sensory processing area, i.e. mitral/tufted cells (MTCs) in the olfactory bulb. In contrast to cholinergic projections, which consistently increased MTC firing, activation of GABAergic fibers from basal forebrain to the olfactory bulb lead to differential modulation effects: while spontaneous MTC activity is mainly inhibited, odor evoked firing is predominantly enhanced. Moreover, sniff triggered averages revealed an enhancement of maximal sniff evoked firing amplitude and an inhibition of firing rates outside the maximal sniff phase. These findings demonstrate that GABAergic neuromodulation affects MTC firing in a bimodal, sensory-input dependent way, suggesting that GABAergic basal forebrain modulation could be an important factor in attention mediated filtering of sensory information to the brain.
CytoTalk:De novoconstruction of signal transduction networks using single-cell RNA-Seq data
Authors: Hu Yuxuan , Peng Tao , Gao Lin , Tan Kai 
Published: March 2020

AbstractSingle-cell technology has opened the door for studying signal transduction in a complex tissue at unprecedented resolution. However, there is a lack of analytical methods forde novoconstruction of signal transduction pathways using single-cell omics data. Here we present CytoTalk, a computational method forde novoconstructing cell type-specific signal transduction networks using single-cell RNA-Seq data. CytoTalk first constructs intracellular and intercellular gene-gene interaction networks using an information-theoretic measure between two cell types. Candidate signal transduction pathways in the integrated network are identified using the prize-collecting Steiner forest algorithm. We applied CytoTalk to a single-cell RNA-Seq data set on mouse visual cortex and evaluated predictions using high-throughput spatial transcriptomics data generated from the same tissue. Compared to published methods, genes in our inferred signaling pathways have significantly higher spatial expression correlation only in cells that are spatially closer to each other, suggesting improved accuracy of CytoTalk. Furthermore, using single-cell RNA-Seq data with receptor gene perturbation, we found that predicted pathways are enriched for differentially expressed genes between the receptor knockout and wild type cells, further validating the accuracy of CytoTalk. In summary, CytoTalk enablesde novoconstruction of signal transduction pathways and facilitates comparative analysis of these pathways across tissues and conditions.
Dynamic inhibition of sensory responses mediated by an olfactory corticofugal system
Authors: Quintela Renata Medinaceli , Bauer Jennifer , Wallhorn Lutz , Brunert Daniela , Rothermel Markus 
Published: March 2020

AbstractProcessing of sensory information is substantially modulated by centrifugal projections from higher cortical areas, yet their behavioral relevance and underlying neural mechanisms remain unclear in most cases. The anterior olfactory nucleus (AON) is part of the olfactory cortex and its extensive connections to lower and higher brain centers put it in a prime position to modulate early sensory information in the olfactory system. Here, we show that optogenetic activation of AON neurons in awake animals was not perceived as an odorant equivalent cue. However, AON activation during odorant presentation reliably suppressed odor responses. This AON mediated effect was fast and constant across odors and concentrations. Likewise, activation of glutamatergic AON projections to the olfactory bulb (OB) transiently inhibited the excitability of mitral/tufted cells (MTCs) that relay olfactory input to cortex. Single-unit MTC recordings revealed that optogenetic activation of glutamatergic AON terminals in the OB transiently decreased sensory-evoked MTC spiking, regardless of the strength or polarity of the sensory response. These findings suggest that glutamatergic AON projections to the OB suppress early olfactory processing by inhibiting OB output neurons and that the AON can dynamically gate sensory throughput to the cortex.Significance StatementThe anterior olfactory nucleus (AON) as an olfactory information processing area sends extensive projections to lower and higher brain centers but the behavioral consequences of its activation have been scarcely investigated. Using behavioral tests in combination with optogenetic manipulation we show that in contrast to what has been suggested previously, the AON does not seem to form odor percepts but instead suppresses odor responses across odorants and concentrations. Furthermore, this study shows that glutamatergic cortical projections to the olfactory bulb suppress olfactory processing by inhibiting output neurons, pointing to a potential mechanisms by which the olfactory cortex can actively and dynamically gate sensory throughput to higher brain centers.HighlightsAON stimulation suppresses odor responses across odorants and concentrationsAON activation is not perceived as an odorant equivalent cueThe AON dynamically shapes olfactory bulb output on a fast timescaleAON input to the olfactory bulb strongly suppresses mitral/tufted cells firing
Reconstruction of microbial haplotypes by integration of statistical and physical linkage in scaffolding
Authors: Cao Chen , He Jingni , Mak Lauren , Perera Deshan , Kwok Devin , Wang Jia , Li Minghao , Mourier Tobias , Gavriliuc Stefan , Greenberg Matthew , Morrissy A. Sorana , Sycuro Laura K. , Yang Guang , Jeffares Daniel C. , Long Quan 
Published: March 2020

ABSTRACTDNA sequencing technologies provide unprecedented opportunities to analyze within-host evolution of microorganism populations. Often, within-host populations are analyzed via pooled sequencing of the population, which contains multiple individuals or ‘haplotypes’. However, current next-generation sequencing instruments, in conjunction with single-molecule barcoded linked-reads, cannot distinguish long haplotypes directly. Computational reconstruction of haplotypes from pooled sequencing has been attempted in virology, bacterial genomics, metagenomics and human genetics, using algorithms based on either cross-host genetic sharing or within-host genomic reads. Here we describe PoolHapX, a flexible computational approach that integrates information from both genetic sharing and genomic sequencing. We demonstrated that PoolHapX outperforms state-of-the-art tools tailored to specific organismal systems, and is robust to within-host evolution. Importantly, together with barcoded linked-reads, PoolHapX can infer whole-chromosome-scale haplotypes from 50 pools each containing 12 different haplotypes. By analyzing real data, we uncovered dynamic variations in the evolutionary processes of within-patient HIV populations previously unobserved in single position-based analysis.
Host-parasite tissue adhesion by a secreted type of β-1,4-glucanase in the parasitic plantPhtheirospermum japonicum
Authors: Kurotani Ken-ichi , Wakatake Takanori , Ichihashi Yasunori , Okayasu Koji , Sawai Yu , Ogawa Satoshi , Suzuki Takamasa , Shirasu Ken , Notaguchi Michitaka 
Published: March 2020

AbstractTissue adhesion between plant species occurs both naturally and artificially. Parasitic plants establish symbiotic relationship with host plants by adhering tissues at roots or stems. Plant grafting, on the other hand, is a widely used technique in agriculture to adhere tissues of two stems. While compatibility of tissue adhesion in plant grafting is often limited within close relatives, parasitic plants exhibit much wider compatibilities. For example, the Orobanchaceae parasitic plantStriga hermonthicais able to infect Poaceae crop plants, causing a serious agricultural loss. Here we found that the model Orobanchaceae parasite plantPhtheirospermum japonicumcan be grafted on to interfamily species, such asArabidopsis, a Brassicaceae plant. To understand molecular basis of tissue adhesion between distant plant species, we conducted comparative transcriptome analyses on both infection and grafting byP. japonicumonArabidopsis. Through gene clustering, we identified genes upregulated during these tissue adhesion processes, which include cell proliferation- and cell wall modification-related genes. By comparing with a transcriptome dataset of interfamily grafting betweenNicotianaandArabidopsis, we identified 9 genes commonly induced in tissue adhesion between distant species. Among them, we showed a gene encoding secreted type of β-1,4-glucanase plays an important role for plant parasitism. Our data provide insights into the molecular commonality between parasitism and grafting in plants.Significance StatementComprehensive sequential RNA-Seq datasets for parasitic infection of the root and grafting of the stem betweenP. japonicumandArabidopsisrevealed that molecular events of parasitism and grafting are substantially different and only share a part of events such as cell proliferation and cell wall modification. This study demonstrated that a secreted type of β-1,4-glucanase gene expressed in cells located at the parasite–host interface as an important factor for parasitism in the Orobanchaceae.
ELP-dependent expression of MCL1 promotes resistance to EGFR inhibition in triple-negative breast cancer cells
Authors: Cruz-Gordillo Peter , Honeywell Megan E. , Leete Thomas , Lee Michael J. 
Published: March 2020

ABSTRACTTargeted therapies for the treatment of cancer are generally thought to exploit oncogene addiction, a phenomenon in which a single oncogene controls both the growth and survival of the tumor cell. Many well-validated examples of oncogene addiction exist; however, the utility of oncogene targeted therapies varies substantially by cancer context, even among cancers in which the targeted oncogene is similarly dysregulated. For instance, epidermal growth factor receptor (EGFR) signaling can be effectively targeted in EGFR-mutant non-small cell lung cancer (NSCLC), but not in triple-negative breast cancer (TNBC), where EGFR is activated to a similar degree. We find that EGFR controls a similar signaling/transcriptional network in TNBC and EGFR-mutant NSCLC cells, but only NSCLC cells respond to EGFR inhibition by activating cell death. To address this paradox and identify mechanisms that contribute to insensitivity to EGFR inhibition in TNBC, we performed a genome-wide CRISPR-Cas9 genetic knockout screen. Our screen identifies the Elongator (ELP) complex as a mediator of insensitivity to EGFR inhibition in TNBC. Depleting ELP proteins caused high levels of apoptotic cell death, in an EGFR inhibition-dependent manner. We find that the tRNA-modifying function of the ELP complex promotes drug insensitivity, by facilitating expression of the anti-apoptotic protein MCL1. Furthermore, pharmacological inhibition of MCL1 synergizes with EGFR inhibition across a panel of genetically diverse TNBC cells. Taken together, we find that TNBC “addiction” to EGFR signaling is masked by the ELP complex, and our study provides an actionable therapeutic strategy to overcome this resistance mechanism by co-targeting EGFR and MCL1.One sentence summaryThe Elongator Protein (ELP) Complex masks TNBC oncogene “addiction” to EGFR signaling, by promoting expression of the anti-apoptotic protein MCL1.