bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity patterns in parasite populations capable for persistence and reinfection with a view towards thehuman cytomegalovirus
Authors: Pokalyuk Cornelia , Görzer Irene 
Published: January 2019

AbstractMany parasites like thecytomegalovirus, HIVandEscherichia coliare capable to persist in and reinfect its host. The evolutionary advantage (if so) of these complicated mechanisms have not been quantitatively analyzed so far. Here we take a first step by investigating a host-parasite model for which these mechanisms are driving the evolution of the parasite population. We consider two variants of the model. In one variant parasite reproduction is directed by balancing selection, in the other variant parasite reproduction is neutral. In the former scenario reinfection and persistence have been shown to sustain the maintenance of diversity in the parasite population in certain parameter regimes (Pokalyuk and Wakolbinger, 2018). Here we analyse the diversity patterns in the latter, neutral scenario. We evaluate the biological relevance of both model variants with respect to thehuman cytomegalovirus(HCMV), an ancient herpesvirus that is carried by a substantial fraction of mankind and manages to maintain a high diversity in its coding regions.
Visual-olfactory integration in the human disease vector mosquito,Aedes aegypti
Authors: Vinauger Clément , Breugel Floris Van , Locke Lauren T. , Tobin Kennedy K.S. , Dickinson Michael H. , Fairhall Adrienne , Akbari Omar S. , Riffell Jeffrey A. 
Published: January 2019

SummaryMosquitoes rely on the integration of multiple sensory cues, including olfactory, visual, and thermal stimuli, to detect, identify and locate their hosts [1–4]. Although we increasingly know more about the role of chemosensory behaviours in mediating mosquito-host interactions [1], the role of visual cues remains comparatively less studied [3], and how the combination of olfactory and visual information is integrated in the mosquito brain remains unknown. In the present study, we used a tethered-flight LED arena, which allowed for quantitative control over the stimuli, to show that CO2exposure affects target-tracking responses, but not responses to large-field visual stimuli. In addition, we show that CO2modulates behavioural responses to visual objects in a time-dependent manner. To gain insight into the neural basis of this olfactory and visual coupling, we conducted two-photon microscopy experiments in a new GCaMP6s-expressing mosquito line. Imaging revealed that the majority of ROIs in the lobula region of the optic lobe exhibited strong responses to small-field stimuli, but showed little response to a large-field stimulus. Approximately 20% of the neurons we imaged were modulated when an attractive odour preceded the visual stimulus; these same neurons also elicited a small response when the odour was presented alone. By contrast, imaging in the antennal lobe revealed no modulation when visual stimuli were presented before or after the olfactory stimulus. Together, our results are the first to reveal the dynamics of olfactory modulation in visually evoked behaviours of mosquitoes, and suggest that coupling between these sensory systems is asymmetrical and time-dependent.
Detecting convergent adaptive amino acid evolution
Authors: Rey Carine , Lanore Vincent , Veber Philippe , Guéguen Laurent , Lartillot Nicolas , Sémon Marie , Boussau Bastien 
Published: January 2019

AbstractIn evolutionary genomics, researchers have taken an interest in identifying in the genomes substitutions that subtend convergent phenotypic adaptations. This is a difficult question to address, because genomes contain billions of sites, many of which have substituted in the lineages where the adaptations took place, and yet are not linked to them. Those extra substitutions may be linked to other adaptations, may be neutral, or may be linked to mutational biases. Furthermore, one can think of various ways of defining substitutions of interest, and various methods that match those definitions have been used, resulting in different sets of candidate substitutions. In this manuscript we first clarify how adaptation to convergent phenotypic evolution can manifest itself in coding sequences. Second, we review methods that have been proposed to detect convergent adaptive evolution in coding sequences and expose the assumptions that underlie them. Finally, we examine their power on simulations of convergent changes, including in the presence of a confounding factor.
Time- and size-resolved bacterial aerosol dynamics in highly polluted air: new clues for haze formation mechanism
Authors: Zhang Ting , Li Xinyue , Wang Minfei , Chen Haoxuan , Yao Maosheng 
Published: January 2019

AbstractAerosol chemistry is often studied without considering microbial involvements. Here, we have applied a high-volume (1 m3/min) aerosol sampler and the Micro-Orifice Uniform Deposit Impactor (NanoMoudi) along with molecular and microscopic methods to investigate time-and size-resolved bacterial aerosol dynamics in air. Under high particulate matter (PM) polluted episodes, bacterial aerosols were detected to have a viability up to 50-70% in the 0.56-1 μm size range, at which elevated levels of SO42−, NO3− and NH4+ were concurrently observed. Engineered or acclimated for both pharmaceuticals and wastewater treatment, bacteria such as Psychrobacter spp., Massilia spp., Acinetobacter lwoffii, Exiguobacterium aurantiacum, and Bacillus megaterium were shown to have experienced massive abundance shifts in polluted air on early mornings and late afternoons, on which were previously reported to witness rapid new particle formation events. For example, Acinetobacter spp. were shown to account for > 96% abundance at a corresponding PM2.5 level of 208 ng/m3. The bacterial aerosol changes corresponded to the observed PM2.5 mass peak shift from 3.2-5.6 μm to the high viability size range of 0.56-1μm. Additionally, it is interesting that elevated levels of soluble Na, Ca, Mg, K, Al, Fe and P elements that are required for bacterial growth were observed to co-occur with those significant bacterial aerosol structure shifts in the air. For particular time-resolved PM2.5 pollution episodes, Acinetobacter and Massilia were shown to alternate in dominating the time-resolved aerosol community structures. The results from a HYSPLIT trajectory model simulation suggested that the role by air mass transport in affecting the observed bacterial aerosol dynamics could be minor. As an evidence, we found that Acinetobacter, Psychrobacter, Exiguobacterium, and Bacillus genera were emitted into the air with a level of > 3000 CFU/m3 from a pharmaceutical plant. In addition, high level of VOCs up to 15,030 ppbv, mainly Acetone (61%) and Acetaldehyde (11%), were also detected in the air inside the plant. All the data including size-resolved viability and time-resolved bacterial aerosol dynamics together with their growth conditions detected in the air suggested that airborne bacteria in the size range of 0.56- 1μm could have played important roles for haze formation in Beijing. The results about time- and size-resolved bacterial aerosol dynamics from this work provide a fresh understanding of aerosol chemistry especially in highly polluted air. It is hoped that these findings could lend a support in future cost-effective air pollution control practices.
Pancreatic tumor organoids for modeling in vivo drug response and discovering clinically-actionable biomarkers
Authors: Huang Ling , Bockorny Bruno , Paul Indranil , Akshinthala Dipikaa , Gandarilla Omar , Bose Arindam , Sanchez-Gonzalez Veronica , Rouse Emily E , Lehoux Sylvain D. , Pandell Nicole , Clohessy John G. , Grossman Joseph , Gonzalez Raul , Pino Sofia Perea Del , Daaboul George , Sawhney Mandeep S. , Freedman Steven D. , Cummings Richard D , Emili Andrew , Muthuswamy Lakshmi B , Hidalgo Manuel , Muthuswamy Senthil K 
Published: January 2019

AbstractPatient-derived models are transforming translational cancer research. It is not clear if the emergence of patient-derived organoid (PDO) models can extend the utility of the widely used patient-derived xenograft (PDX). In addition, the utility of PDO models for serum biomarker discovery is not known. Here, we demonstrate that PDO models recapitulate the genomics, cell biology, glycomics and drug responses observed in PDX models. Furthermore, we demonstrate the applicability of PDO models for identification of N-glycans that are enriched in the glycome of pancreatic ductal adenocarcinoma (PDAC). Surprisingly, among all the glycans observed in PDX and PDOs, a core set of 57 N-glycans represent 50-94% of the relative abundance of all N-glycans detected, suggesting that only a subset of glycans dominate the cell surface landscape in PDAC. In addition, we outline a tumor organoid-based pipeline to identify surface proteins in extracellular vesicles (EV) from media supernatant of PDO cultures. When combined with the affinity-based validation platform, the EV surface proteins discovered in PDOs are effective in differentiating patients with PDAC from those with benign pancreatitis in the clinic, identifying PDO as powerful discovery platform for serum biomarkers. Thus, PDOs extend the utility of the archival collections of PDX models for translational research and function as a powerful platform for identification of clinically-actionable biomarkers in patients blood.Significance statementTumor organoids extend the utility of PDX models as platforms for investigating drug response, glycosylation changes and function as new platforms for discovering blood-based biomarkers
CRISPR interference-based platform for multimodal genetic screens in human iPSC-derived neurons
Authors: Tian Ruilin , Gachechiladze Mariam A. , Ludwig Connor H. , Laurie Matthew T. , Hong Jason Y. , Nathaniel Diane , Prabhu Anika V. , Fernandopulle Michael S. , Patel Rajan , Abshari Mehrnoosh , Ward Michael E. , Kampmann Martin 
Published: January 2019

SUMMARYCRISPR/Cas9-based functional genomics have transformed our ability to elucidate mammalian cell biology. However, most previous CRISPR-based screens were conducted in cancer cell lines, rather than healthy, differentiated cells. Here, we describe a CRISPR interference (CRISPRi)-based platform for genetic screens in human neurons derived from induced pluripotent stem cells (iPSCs). We demonstrate robust and durable knockdown of endogenous genes in such neurons, and present results from three complementary genetic screens. First, a survival-based screen revealed neuron-specific essential genes and genes that improved neuronal survival upon knockdown. Second, a screen with a single-cell transcriptomic readout uncovered several examples of genes whose knockdown had strikingly cell-type specific consequences. Third, a longitudinal imaging screen detected distinct consequences of gene knockdown on neuronal morphology. Our results highlight the power of unbiased genetic screens in iPSC-derived differentiated cell types and provide a platform for systematic interrogation of normal and disease states of neurons.
A rabbit monoclonal antibody against the antiviral and cancer genomic DNA mutating enzyme APOBEC3B
Authors: Brown William L. , Law Emily K. , Carpenter Michael A. , Argyris Prokopios P. , Levin-Klein Rena , Ranum Alison N. , Molan Amy M. , Forster Colleen L. , Anderson Brett D. , Lackey Lela , Harris Reuben S. 
Published: January 2019

AbstractThe DNA cytosine deaminase APOBEC3B (A3B) is normally an antiviral factor in the innate immune response. However, A3B has been implicated in cancer mutagenesis, particularly in solid tumors of the bladder, breast, cervix, head/neck, and lung. Here, we report data on the generation and characterization of a rabbit monoclonal antibody (mAb) for human A3B through a series of immunoblot, immunofluorescence microscopy, and immunohistochemistry experiments. Positive results indicate that one mAb, 5210-87-13, will be useful for fundamental research in virology and cancer biology and that immunohistochemical quantification of A3B enzyme levels may constitute a clinical biomarker for tumor evolvability and differential treatment.
Active site plasticity and possible modes of chemical inhibition of the human DNA deaminase APOBEC3B
Authors: Shi Ke , Demir Özlem , Carpenter Michael A. , Banerjee Surajit , Harki Daniel A. , E. Amaro Rommie , Harris Reuben S. , Aihara Hideki 
Published: January 2019

AbstractThe single-stranded DNA cytosine deaminase APOBEC3B (A3B) functions in innate immunity against viruses, but is also strongly implicated in eliciting mutations in cancer genomes. Because of the critical role of A3B in promoting virus and tumor evolution, small molecule inhibitors are desirable. However, there is no reported structure for any of the APOBEC3-family enzymes in complex with a small molecule bound in the active site, which hampers the development of small molecules targeting A3B. Here we report high-resolution structures of an active A3B catalytic domain chimera with loop 7 residues exchanged with those from the corresponding region of APOBEC3G (A3G). The structures reveal novel open conformations lacking the catalytically essential zinc ion, with the highly conserved active site residues extensively rearranged. These inactive conformations are stabilized by 2-pyrimidone or an iodide ion bound in the active site. Molecular dynamics simulations corroborate the remarkable plasticity of the engineered active site and identify key interactions that stabilize the native A3B active site. These data provide insights into A3B active site dynamics and suggest possible modes of its inhibition by small molecules, which would aid in rational design of selective A3B inhibitors for constraining virus and tumor evolution.
Computing Hubs in the Hippocampus and Cortex
Authors: Clawson Wesley , Vicente Ana F. , Bernard Christophe , Battaglia Demian , Quilichini Pascale P 
Published: January 2019

AbstractNeural computation, which relies on the active storage and sharing of information, occurs within large neuron networks in the highly dynamic context of varying brain states. Whether such functions are performed by specific subsets of neurons and whether they occur in specific dynamical regimes remain poorly understood. Using high density recordings in the hippocampus, medial entorhinal and medial prefrontal cortex of the rat, we identify computing microstates, or discreet epochs, in which specific computing hub neurons perform well defined storage and sharing operations in a brain state-dependent manner. We retrieve a multiplicity of distinct computing microstates within each global brain state, such as REM and nonREM sleep. Half of recorded neurons act as computing hubs in at least one microstate, suggesting that functional roles are not firmly hardwired but dynamically reassigned at the second timescale. We identify sequences of microstates whose temporal organization is dynamic and stands between order and disorder. We propose that global brain states constrain the language of neuronal computations by regulating the syntactic complexity of these microstate sequences.
Airway epithelial integrin β4 suppresses allergic inflammation by decreasing CCL17 production
Authors: Yuan Lin , Zhang Xun , Yang Ming , Zou Yizhou , Xiang Yang , Qu Xiangping , Liu Huijun , Du Xizi , Wang Leyuan , Wu Shuangyan , Wu Mengping , Qin Ling , Qin Qingwu , Qin Xiaoqun , Liu Chi 
Published: January 2019

AbstractAirway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin β4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. Specific ITGB4 deficiency in AECs induces exaggerated Th2 responses, severe allergen-induced airway inflammation and airway hyperresponsiveness (AHR) in mouse model of allergic asthma. However, the underlying mechanisms remain unexplored. In this study, we determine the role of ITGB4 of AECs in the regulation of Th2 response and in the induction of asthma and identify the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated Th2 cells infiltration, inflammation and AHR and higher production of CCL17 in HDM treated mice. ITGB4-regulated CCL17 production in AECs was regulated by EGFR, ERK and NF-κB pathways. EFGR-antagonist treatment or the neutralization of CCL17 by antibody inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated that ITGB4 of AECs negatively regulates the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway.
CHCHD4 regulates a proliferation-EMT switch in tumour cells, through respiratory complex I mediated metabolism
Authors: Thomas Luke W. , Esposito Cinzia , Stephen Jenna M. , Costa Ana S. H. , Frezza Christian , Blacker Thomas S. , Szabadkai Gyorgy , Ashcroft Margaret 
Published: January 2019

ABSTRACTBACKGROUNDMitochondrial metabolism involves oxidative phosphorylation (OXPHOS) via the respiratory chain and is required for the maintenance of tumour cell proliferation and regulation of epithelial–mesenchymal transition (EMT)-related phenotypes through mechanisms that are not fully understood. The essential mitochondrial import protein coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) controls respiratory chain complex activity and oxygen consumption, and regulates the growth of tumours in vivo. In this study we interrogate the role of CHCHD4-regulated respiratory chain activity and metabolism in tumour cell proliferation and EMT-related phenotypes.RESULTSWe show that CHCHD4 is essential for the proliferation of tumour cells irrespective of their aetiology. In human tumours, elevated CHCHD4 expression is correlated with a mitochondrial OXPHOS gene signature and with a proliferative gene signature associated with the mTORC1 signalling pathway. Elevated CHCHD4 increases tumour cell proliferation, in a manner that is dependent on complex I (CI) activity, glutamine consumption and mTORC1 activation. CHCHD4 expression is inversely correlated with EMT gene expression both in vitro and in vivo. Finally, we show CHCHD4 regulates the intracellular distribution of the EMT marker vimentin, in a CI-mediated manner.CONCLUSIONSCHCHD4 regulates tumour cell proliferation and metastatic (EMT-related) phenotypes through its control of CI-mediated mitochondrial metabolism.
Bacterioplankton dynamics driven by inter-annual variation in phytoplankton spring bloom communities in the Baltic Sea
Authors: Camarena-Gómez María Teresa , Ruiz-González Clara , Piiparinen Jonna , Lipsewers Tobias , Sobrino Cristina , Logares Ramiro , Spilling Kristian 
Published: January 2019

AbstractIn the Baltic Sea, climate change has caused shifts in the phytoplankton spring bloom communities with co-occurrence of diatoms and dinoflagellates. Such changes likely affect the composition and function of associated bacterioplankton, key members of the carbon cycling, although the actual effects are unknown. To understand how changes in phytoplankton impact on bacterioplankton composition and function, we analysed bacterioplankton communities and their production during different phases of the spring bloom in four consecutive years across the Baltic Sea, and related them to environmental variables. Phytoplankton communities varied largely in composition, modifying the taxonomic structure and richness of the associated bacterioplankton assemblages. In presence of certain diatoms (Achnanthes taeniata, Skeletonema costatum and Chaetoceros spp.), bacterial production and diversity were high and with more relative abundance of Flavobacteriia, Gammaproteobacteria and Betaproteobacteria. This bacterial community structure correlated positively with high diatom biomass and with high bacterial production rates. In contrast, during dinoflagellate-dominated blooms or when the diatom Thalassiosira baltica was abundant, both bacterial production rates and diversity were low, with bacterial communities dominated by SAR11 and Rhodobacteraceae. Our results demonstrate that, changes in the phytoplankton spring bloom will have profound consequences on bacterial community structure and their role in carbon cycling.
Virus-host coexistence in phytoplankton through the genomic lens
Authors: Sheree Yau , Krasovec Marc , Rombauts Stephane , Groussin Mathieu , Benites L. Felipe , Vancaester Emmelien , Aury Jean-Marc , Derelle Evelyne , Desdevises Yves , Escande Marie-Line , Grimsley Nigel , Guy Julie , Moreau Hervé , Sanchez-Brosseau Sophie , van de Peer Yves , Vandepoele Klaas , Gourbiere Sebastien , Piganeau Gwenael 
Published: January 2019

AbstractPhytoplankton-virus interactions are major determinants of geochemical cycles in the oceans. Viruses are responsible for the redirection of carbon and nutrients away from larger organisms back towards microorganisms via the lysis of microalgae in a process coined the ‘viral shunt’. Virus-host interactions are generally expected to follow ‘boom and bust’ dynamics, whereby a numerically dominant strain is lysed and replaced by a virus resistant strain. Here, we isolated a microalga and its infective nucleo-cytoplasmic large DNA virus (NCLDV) concomitantly from the environment in the surface NW Mediterranean Sea,Ostreococcus mediterraneus, and show continuous growth in culture of both the microalga and the virus. Evolution experiments through single cell bottlenecks demonstrate that, in the absence of the virus, susceptible cells evolve from one ancestral resistant single cell, and vice–versa; that is that resistant cells evolve from one ancestral susceptible cell. This provides evidence that the observed sustained viral production is the consequence of a minority of virus-susceptible cells. The emergence of these cells is explained by low-level phase switching between virus-resistant and virus-susceptible phenotypes, akin to a bet hedging strategy. Whole genome sequencing and analysis of the ~14 Mb microalga and the ~200 kb virus points towards ancient speciation of the microalga within theOstreococcusspecies complex and frequent gene exchanges between prasinoviruses infectingOstreococcusspecies. Re-sequencing of one susceptible strain demonstrated that the phase switch involved a large 60 Kb deletion of one chromosome. This chromosome is an outlier chromosome compared to the streamlined, gene dense, GC-rich standard chromosomes, as it contains many repeats and few orthologous genes. While this chromosome has been described in three different genera, its size increments have been previously associated to antiviral immunity and resistance in another species from the same genus. Mathematical modelling of this mechanism predicts microalga–virus population dynamics consistent with the observation of continuous growth of both virus and microalga. Altogether, our results suggest a previously overlooked strategy in phytoplankton–virus interactions.