bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping Interactome Networks of FOSL1 and FOSL2 in Human Th17 Cells
Authors: Shetty Ankitha , Bhosale Santosh D. , Tripathi Subhash Kumar , Buchacher Tanja , Biradar Rahul , Rasool Omid , Moulder Robert , Galande Sanjeev , Lahesmaa Riitta 
Published: May 2021

ABSTRACTDysregulated function of Th17 cells has implications in immunodeficiencies and autoimmune disorders. Th17 cell-differentiation is orchestrated by a complex network of transcription factors, including several members of the activator protein (AP-1) family. Among these, FOSL1 and FOSL2 influence the effector responses of Th17 cells. However, the molecular mechanisms underlying these functions are unclear, owing to the poorly characterized protein interaction networks of these factors. Here, we establish the first interactomes of FOSL1 and FOSL2 in human Th17 cells, using affinity purification–mass spectrometry analysis. In addition to the known JUN proteins, we identified several novel binding partners of FOSL1 and FOSL2. Gene ontology analysis found a major fraction of these interactors to be associated with RNA binding activity, which suggests new mechanistic links. Intriguingly, 29 proteins were found to share interactions with FOSL1 and FOSL2, and these included key regulators of Th17-fate. We further validated the binding partners identified in this study by using parallel reaction monitoring targeted mass-spectrometry and other methods. Our study provides key insights into the interaction-based signaling mechanisms of FOSL factors that potentially govern Th17 cell-differentiation and associated pathologies.
Flexibility of a mammalian lipidome — insights from mouse lipidomics
Authors: Surma Michał A. , Gerl Mathias J. , Herzog Ronny , Helppi Jussi , Simons Kai , Klose Christian 
Published: May 2021

ABSTRACTLipidomics has become an indispensable method for the quantitative assessment of lipid metabolism in basic, clinical, and pharmaceutical research. It allows for the generation of information-dense datasets in a large variety of experimental setups and model organisms. Previous studies, mostly conducted in mice (Mus musculus), have shown a remarkable specificity of the lipid compositions of different cell types, tissues, and organs. However, a systematic analysis of the overall variation of the mouse lipidome is lacking. To fill this gap, in the present study, the effect of diet, sex, and genotype on the lipidomes of mouse tissues, organs, and bodily fluids has been investigated. Baseline quantitative lipidomes consisting of 796 individual lipid molecules belonging to 24 lipid classes are provided for 10 different sample types. Furthermore, the susceptibility of lipidomes to the tested parameters is assessed, providing insights into the organ-specific lipidomic plasticity and flexibility. This dataset provides a valuable resource for basic and pharmaceutical researchers working with murine models and complements existing proteomic and transcriptomic datasets. It will inform experimental design and facilitate interpretation of lipidomic datasets.
Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as the primary mechanism of vaccine-induced protection against HIV-1
Authors: Shangguan Shida , Ehrenberg Philip K. , Geretz Aviva , Yum Lauren , Kundu Gautam , May Kelly , Fourati Slim , Nganou-Makamdop Krystelle , Williams LaTonya D. , Sawant Sheetal , Lewitus Eric , Pitisuttithum Punnee , Nitayaphan Sorachai , Chariyalertsak Suwat , Rerks-Ngarm Supachai , Rolland Morgane , Douek Daniel , Gilbert Peter , Tomaras Georgia D. , Michael Nelson , Vasan Sandhya , Thomas Rasmi 
Published: May 2021

AbstractA gene signature previously correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus (SIV) and SHIV challenge models in non-human primates (NHP). In this report we investigated presence of this signature as a correlate of reduced risk in human clinical trials and potential mechanism for protection. The absence of this gene signature in the DNA/rAd5 human vaccine trial which did not show efficacy, strengthens our hypothesis that this signature is only enriched in studies that demonstrated protection. This gene signature was enriched in the partially effective RV144 human trial that administered the ALVAC/protein vaccine, and we find that the signature associates with both decreased risk of HIV-1 acquisition and increased vaccine efficacy. Total RNA-seq in a clinical trial that used the same vaccine regimen as the RV144 HIV vaccine implicated antibody-dependent cellular phagocytosis (ADCP) as a potential mechanism of vaccine protection. CITE-seq profiling of 53 surface markers and transcriptomes of 53,777 single cells from the same trial, showed that genes in this signature were primarily expressed in cells belonging to the myeloid lineage including monocytes, which are major effector cells for ADCP. The consistent association of this transcriptome signature with vaccine efficacy represents a tool both to identify potential mechanisms, as with ADCP here, and to screen novel approaches to accelerate development of new vaccine candidates.
Temporal dynamics of microbial transcription in wetted hyperarid desert soils
Authors: León-Sobrino Carlos , Ramond Jean-Baptiste , Coclet Clément , Kapitango Ritha-Meriam , Maggs-Kölling Gillian , Cowan Don A. 
Published: May 2021

AbstractRainfall is rare in hyperarid deserts but, when it occurs, it triggers large biological responses which are considered to be essential for the long-term maintenance of biodiversity. In such environments, microbial communities have major roles in nutrient cycling, but their functional responses to short-lived resource opportunities are poorly understood. We used whole community metatranscriptomic data to demonstrate structured and sequential functional responses in desiccated desert soils to a simulated rainfall event over a seven-day time frame. Rapid transcriptional activation of Actinobacteria, Alpha-proteobacteria and phage transcripts was followed by a marked increase in protist and myxobacterial activity, before returning to the original state. In functional terms, motility systems were activated in the early phases, whereas competition-toxicity systems increased in parallel to the activity from predators and the drying of soils. The dispersal-predation dynamic was identified as a central driver of microbial community responses to watering. Carbon fixation mechanisms that were active under dry condition were rapidly down-regulated in wetted soils, and only reactivated on a return to a near-dry state, suggesting a reciprocal balance between carbon fixation and fixed-carbon acquisition processes. Water addition induced a general reduction in the transcription of stress response genes, most prominently HSP20, indicating that this chaperone is particularly important for life in desiccated ecosystems. Based on these data, we propose a rainfall response model for desert soil microbiomes.
Transient ribosome slowdown at the decoding step triggers mRNA degradation independent of Znf598 in zebrafish
Authors: Mishima Yuichiro , Han Peixun , Kimura Seisuke , Iwasaki Shintaro 
Published: May 2021

AbstractThe control of mRNA stability plays a central role in regulating gene expression patterns. Recent studies have revealed that codon composition in the open reading frame (ORF) determines mRNA stability in multiple organisms. Based on genome-wide correlation approaches, this previously unrecognized role of the genetic code is attributable to the kinetics of the codon-decoding process by the ribosome. However, complementary experimental analysis is required to define the codon effects on mRNA stability apart from the related cotranslational mRNA decay pathways such as those triggered by aberrant ribosome stalls. In the current study, we performed a set of reporter-based analyses to define codon-mediated mRNA decay and ribosome stall-dependent mRNA decay in zebrafish embryos. Our analysis showed that the effect of codons on mRNA stability stems from the decoding process, independent of Znf598 and stall-dependent mRNA decay. We propose that codon-mediated mRNA decay is triggered by transiently slowed ribosomes engaging in a productive translation cycle in zebrafish embryos.
Passive sampling of environmental DNA in aquatic environments using 3D-printed hydroxyapatite samplers
Authors: Verdier Héloïse , Konecny Lara , Marquette Christophe , Reveron Helen , Tadier Solène , Grémillard Laurent , Barthès Amélie , Datry Thibault , Bouchez Agnès , Lefébure Tristan 
Published: May 2021

AbstractThe study of environmental DNA released by aquatic organisms in their habitat offers a fast, non-invasive and sensitive approach to monitor their presence. Common eDNA sampling methods such as filtration and precipitation are time consuming, require human intervention and are not applicable to a wide range of habitats such as turbid waters and poorly-accessible environments. To circumvent these limitations, we propose to use the binding properties of minerals to create a passive eDNA sampler.We have designed 3D-printed samplers made of hydroxyapatite (HAp samplers), a mineral known for its high binding affinity with DNA. The shape and the geometry of the samplers have been designed to facilitate their handling in laboratory and field. Here we describe and test the ability of HAp samplers to recover artificial DNA and eDNA.We show that HAp samplers efficiently recover DNA and are effective even on small amounts of eDNA (<1 ng). However, we also observed large variations in the amount of DNA recovered even under controlled conditions.By better understanding the physico-chemical interactions between DNA and the HAp sampler surface, one could improve the repeatability of the sampling process and provide an easy-to-use eDNA sampling tool for aquatic environments.
Ecdysteroids as natural doping substances in the blood of insectivorous bats
Authors: Hornok Sándor , Berkecz Róbert , Sós Endre , Sándor Attila D. , Körmöczi Tímea , Solymosi Norbert , Kontschán Jenő , Hunyadi Attila 
Published: May 2021

AbstractBats have deserved much scientific attention due to their biological-ecological properties and increasingly recognized epidemiological significance. Ecdysteroids are insect-molting hormones that (under experimental conditions) have stimulating and anabolic effects in mammals, including humans. Therefore, these biologically active compounds are currently under consideration by the World Anti-Doping Agency (WADA) to become doping-controlled substances. Previously we demonstrated that low to high concentrations of ecdysteroids appear in the blood of insectivorous passerine birds. Since passerine birds and echolocating bats share several adaptive mechanisms in connection with flying, and insectivorism is also among their common traits, we hypothesized that ecdysteroids might also be present in the blood of insectivorous bats. To test this hypothesis, blood samples of eight insectivorous bat species were collected and analyzed for the presence of ecdysteroids with highly sensitive targeted ultra-high-performance liquid chromatography coupled to high-resolution quadrupole-orbitrap mass spectrometry method (UHPLC-HRMS). The results supported our hypothesis, because nine ecdysteroids were detected in bat blood. The spectrum of these ecdysteroids was similar in those bat species which have their most preferred food items from the same insect order, supporting insects as the most likely source of these hormones. It was also shown that the spectrum of blood-borne ecdysteroids was broader in the autumn than in the summer, and higher concentrations of 20-hydroxyecdysone were measured in samples of large size bat species in comparison with small size ones. Based on the known physiologic effects of ecdysteroids, we postulate that these results might have implications on the metabolic rate and parasite burdens of insectivorous bats.
Actin isovariant ACT7 controls root meristem development in Arabidopsis through modulating auxin and ethylene responses
Authors: Numata Takahiro , Sugita Kenji , Rahman Arifa Ahamed , Rahman Abidur 
Published: May 2021

AbstractMeristem is the most functionally dynamic part in a plant body. The shaping of the meristem requires constant cell division and cell elongation, which are influenced by hormones and cell cytoskeletal component, actin. Although the roles of hormones in modulating meristem development have been extensively studied, the role of actin in this process is still elusive. Using the single and double mutants of the vegetative class actin, we demonstrate that actin isovariant ACT7 plays an important role in root meristem development. In absence of ACT7, but not ACT8 and ACT2, depolymerization of actin was observed. Consistently, act7 mutant showed reduced cell division, cell elongation, and meristem length. Intracellular distribution and trafficking of auxin transport proteins in the actin mutants revealed that ACT7 specifically functions in root meristem to facilitate the trafficking of auxin efflux carriers PIN1 and PIN2, and consequently the transport of auxin. Compared with act7, act7act8 double mutant shows slightly enhanced phenotypic response and altered intracellular trafficking. The altered distribution of auxin in act7 and act7act8 affects the response of the roots to ethylene but not to cytokinin. Collectively, our results suggest that ACT7 dependent auxin-ethylene response plays a key role in controlling Arabidopsis root meristem development.
Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection
Authors: Brügger Melanie , Démoulins Thomas , Barut G. Tuba , Zumkehr Beatrice , Oliveira Esteves Blandina I. , Mehinagic Kemal , Haas Quentin , Schögler Aline , Rameix-Welti Marie-Anne , Eléouët Jean-François , Moehrlen Ueli , Marti Thomas M. , Schmid Ralph A. , Summerfield Artur , Posthaus Horst , Ruggli Nicolas , Hall Sean R. R. , Alves Marco P. 
Published: May 2021

ABSTRACTLung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche and fundamental regulators of homeostasis and regeneration. We interrogated their function during virus-induced lung injury using the highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. We applied complementary approaches with primary pediatric LR-MSCs and a state-of-the-art model of human RSV infection in lamb. Remarkably, RSV-infection of pediatric LR-MSCs led to a robust activation, characterized by a strong antiviral and pro-inflammatory phenotype combined with mediators related to T cell function. In line with this, following in vivo infection, RSV invades and activates LR-MSCs, resulting in the expansion of the pulmonary MSC pool. Moreover, the global transcriptional response of LR-MSCs appears to follow RSV disease, switching from an early antiviral signature to repair mechanisms including differentiation, tissue remodeling, and angiogenesis. These findings demonstrate the involvement of LR-MSCs during virus-mediated acute lung injury and may have therapeutic implications.AUTHOR SUMMARYThis work identifies a novel function of lung-resident MSCs during virus-induced acute lung injury. These findings contribute to the understanding of host response and lung repair mechanisms during a highly prevalent clinical situation and may have therapeutic implications.
Mechanistic insights into dideoxygenation in gentamicin biosynthesis
Authors: Li Sicong , Bury Priscila dos Santos , Huang Fanglu , Guo Junhong , Sun Guo , Reva Anna , Huang Chuan , Jian Xinyun , Li Yuan , Zhou Jiahai , Deng Zixin , Leeper Finian J. , Leadlay Peter F. , Dias Marcio V. B. , Sun Yuhui 
Published: May 2021

AbstractGentamicin is an important aminoglycoside antibiotic used for treatment of infections caused by Gram-negative bacteria. Although most of the biosynthetic pathway of gentamicin has been elucidated, a remaining intriguing question is how the intermediates JI-20A and JI-20B undergo a dideoxygenation to form gentamicin C complex. Here we show that the dideoxygenation process starts with GenP-catalyzed phosphorylation of JI-20A and JI-20Ba. The phosphorylated products are converted to C1a and C2a by concerted actions of two PLP (pyridoxal 5’-phosphate)-dependent enzymes: elimination of water and then phosphate by GenB3 and double bond migration by GenB4. Each of these reactions liberates an imine which hydrolyses to a ketone or aldehyde and is then re-aminated by GenB3 using an amino donor. Crystal structures of GenB3 and GenB4 have guided site-directed mutagenesis to reveal crucial residues for the enzymes’ functions. We propose catalytic mechanisms for GenB3 and GenB4, which shed new light on the already unrivalled catalytic versatility of PLP-dependent enzymes.
A sex-specific evolutionary interaction betweenADCY9andCETP
Authors: Gamache Isabel , Legault Marc-André , Grenier Jean-Christophe , Sanchez Rocio , Rhéaume Eric , Asgari Samira , Barhdadi Amina , Zada Yassamin Feroz , Trochet Holly , Luo Yang , Lecca Leonid , Murray Megan , Raychaudhuri Soumya , Tardif Jean-Claude , Dubé Marie-Pierre , Hussin Julie G. 
Published: May 2021

AbstractPharmacogenomic studies have revealed associations between rs1967309 in the adenylyl cyclase type 9 (ADCY9) gene and clinical responses to the cholesteryl ester transfer protein (CETP) modulator dalcetrapib, however, the mechanism behind this interaction is still unknown. Here, we characterized selective signals at the locus associated with the pharmacogenomic response in human populations and we show that rs1967309 region exhibits signatures of positive selection in several human populations. Furthermore, we identified a variant inCETP, rs158477, which is in long-range linkage disequilibrium with rs1967309 in the Peruvian population. The signal is mainly seen in males, a sex-specific result that is replicated in the LIMAA cohort of over 3,400 Peruvians. Analyses of RNA-seq data further suggest an epistatic interaction onCETPexpression levels between the two SNPs in multiple tissues, which also differs between males and females. We also detected interaction effects of the two SNPs with sex on cardiovascular phenotypes in the UK Biobank, in line with the sex-specific genotype associations found in Peruvians at these loci. We propose thatADCY9andCETPcoevolved during recent human evolution due to sex-specific selection, which points towards a biological link between dalcetrapib’s pharmacogeneADCY9and its therapeutic targetCETP.
Do host-consumed resources increase endoparasitic but decrease ectoparasitic infections?
Authors: Shayhorn Brin , Ramsay Chloe , Medina Kristi , Sauer Erin , Rohr Jason R. 
Published: May 2021

AbstractHabitat loss and disease outbreak play a major role in the decline of biodiversity. Habitat degradation is often associated with reduced food resources, which can lead to less investment in host immunity and increased infections. However, pathogens use host resources for replication and pathogen traits, such as infecting hosts internally or short generation times, might allow pathogens to rapidly capitalize on host-consumed nutrients. Thus, it is unclear whether increased food consumption by hosts should reduce or amplify pathogen levels. We conducted experiments on Cuban treefrogs (Osteopilus septentrionalis) to test how food availability affects infection levels of Ranavirus and the fungal pathogen Batrachochytrium dendrobatidis (Bd), which are both associated with mass die-offs of amphibians. Given that Ranavirus is an endoparasite with a much shorter generation time than the ectoparasitic Bd, we postulated that Ranavirus might be able to capitalize on host-consumed resources more quickly than Bd. We hypothesized that increased food availability to hosts might reduce Bd infections more than Ranavirus infections. As predicted, augmenting food access decreased Bd infection intensity, but increased Ranavirus infection intensity. Future work should assess whether pathogen traits, such as generation time and endo- versus ectoparasitism, generally affect whether food resources more positively benefit hosts or pathogens.
Bilingual speakers’ enhanced monitoring can slow them down
Authors: Markiewicz Roksana , Mazaheri Ali , Krott Andrea 
Published: May 2021

AbstractPerformance differences between bilinguals and monolinguals on conflict tasks can be affected by the balance of various sub-processes such as conflict monitoring and allocation of attentional resources for stimulus categorisation. Here we investigated the effect of bilingualism on these sub-processes during a conflict task with medium monitoring demand. We examined the behavioural responses and evoked potentials from bilinguals and monolinguals during a flanker task with 25% incongruent trials. We analysed behavioural differences by means of averaged response times and ex-Gaussian analyses of response time distributions. For the evoked potentials we focused on N2 (reflecting conflict monitoring) and P3 responses (reflecting allocation of attentional resources for cognitive control). We found that bilinguals had significantly longer response distribution tails compared to monolinguals. Additionally, bilinguals exhibited a more pronounced N2 and smaller P3 components compared to monolinguals, independent of experimental condition, suggesting a different balance of sub-processes for the two groups. It is suggested that bilinguals engaged more strongly in monitoring processes, leading to the allocation of fewer attentional resources during stimulus categorisation. Importantly, N2 amplitudes were positively and P3 amplitudes negatively related to the length of response distribution tails. We postulate that these results reflect an overactive monitoring system in bilinguals. This enhanced monitoring led to reduced engagement of attentional resources for stimulus categorisation, but also occasionally to slow responses. These results suggest that changes of the cognitive control system due to bilingual experience can change the balance of processes during conflict tasks, potentially leading to a small behavioural disadvantage.
in silicoAssessment of Antibody Drug Resistance to Bamlanivimab of SARS-CoV-2 Variant B.1.617
Authors: Zhang Leili , Huynh Tien , Luan Binquan 
Published: May 2021

AbstractThe highly infectious SARS-CoV-2 variant B.1.617 with double mutations E484Q and L452R in the receptor binding domain (RBD) of SARS-CoV-2’s spike protein is worrisome. Demonstrated in crystal structures, the residues 452 and 484 in RBD are not in direct contact with interfacial residues in the angiotensin converting enzyme 2 (ACE2). This suggests that albeit there are some possibly nonlocal effects, the E484Q and L452R mutations might not significantly affect RBD’s binding with ACE2, which is an important step for viral entry into host cells. Thus, without the known molecular mechanism, these two successful mutations (from the point of view of SARS-CoV-2) can be hypothesized to evade human antibodies. Usingin silicoall-atom molecular dynamics (MD) simulation as well as deep learning (DL) approaches, here we show that these two mutations significantly reduce the binding affinity between RBD and the antibody LY-CoV555 (also named as Bamlanivimab) that was proven to be efficacious for neutralizing the wide-type SARS-CoV-2. With the revealed molecular mechanism on how L452R and E484K evade LY-CoV555, we expect that more specific therapeutic antibodies can be accordingly designed and/or a precision mixing of antibodies can be achieved in a cocktail treatment for patients infected with the variant B.1.617.Abstract Figure