bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mental imagery can generate and regulate acquired differential fear conditioned reactivity
Authors: Greening Steven G. , Lee Tae-Ho , Burleigh Lauryn , Grégoire Laurent , Robinson Tyler , Jiang Xinrui , Mather Mara , Kaplan Jonas 
Published: February 2021

ABSTRACTMental imagery is an important tool in the cognitive control of emotion. The present study tests the prediction that visual imagery can generate and regulate differential fear conditioning via the activation and prioritization of stimulus representations in early visual cortices. We combined differential fear conditioning with manipulations of viewing and imagining basic visual stimuli in humans. We discovered that mental imagery of a fear-conditioned stimulus compared to imagery of a safe conditioned stimulus generated a significantly greater conditioned response as measured by self-reported fear, the skin conductance response, and right anterior insula activity (experiment 1). Moreover, mental imagery effectively down- and up-regulated the fear conditioned responses (experiment 2). Multivariate classification using the functional magnetic resonance imaging data from retinotopically defined early visual regions revealed significant decoding of the imagined stimuli in V2 and V3 (experiment 1) but significantly reduced decoding in these regions during imagery-based regulation (experiment 2). Together, the present findings indicate that mental imagery can generate and regulate a differential fear conditioned response via mechanisms of the depictive theory of imagery and the biased-competition theory of attention. These findings also highlight the potential importance of mental imagery in the manifestation and treatment of psychological illnesses.
Landscape composition mediates suppression of major pests by natural enemies in conventional cruciferous vegetables
Authors: Zhang Jie , You Shijun , Niu Dongsheng , Guaman Karla Giovana Gavilanez , Wang Ao , Saqib Hafiz Sohaib Ahmed , He Weiyi , Yu Yuan , Yang Guang , Pozsgai Gabor , You Minsheng 
Published: February 2021

ABSTRACTBackgroundConservation biological control provides an environment-friendly approach to improve the efficacy of natural enemies. Although numerous studies have demonstrated the potential of semi-natural habitats in promoting biological control in organic or unsprayed agroecosystems, few studies were conducted in conventional agricultural fields. In this study, we investigated the effects of landscape composition on the major pests of cruciferous vegetables and on the assemblages of their natural enemies in southeastern China.ResultsHabitat diversity, particularly increasing grassland proportion in the landscape, had a positive impact in controlling both small-sized pests (aphids, leaf miners, thrips and flea beetles) andPlutella xylostella. This increasing proportion also promoted greater abundance and diversity of canopy-dwelling predators, more forests supported a higher diversity of airborne enemies (parasitoids and canopy-dwelling predators) as well as a higher abundance of ground-dwelling predators. A general increase in habitat diversity was beneficial to parasitoids and ground-dwelling predators. Additionally, the proportion of forest, grassland, and non-cruciferous vegetable area, as well as habitat diversity, affected the compositions of natural enemy communities. Moreover, inconsistent effects of non-cruciferous and grassland habitats were found between sampling regions for small-sized pests and canopy-dwelling predators. Moreover, the scale at which pests and natural enemies’ abundance and richness responded most to landscape composition varied with their feeding range and dispersal ability.ConclusionOur study provides evidence that increasing the amount of semi-natural habitats and habitat diversity can result in lower pest and higher natural enemy abundance in conventional cruciferous agroecosystems. Regional conditions and spatial scales also should be considered in designing the agricultural landscape mosaic.
Cancer relevance of human genes
Authors: Qing Tao , Mohsen Hussein , Cannataro Vincent L. , Marczyk Michal , Rozenblit Mariya , Foldi Julia , Murray Michael F. , Townsend Jeffrey P. , Kluger Yuval , Gerstein Mark , Pusztai Lajos 
Published: February 2021

AbstractBackgroundIt is unclear how many of genes contribute to the biology of cancer. We hypothesize that genes that interact with core cancer gene (CCG) in a protein-protein interaction network (PPI) may have functional importance.MethodsWe categorized genes into 1- (n=6791), 2- (n=7724), 3- (n=1587), and >3-steps (n=362) removed from the nearest CCG in the STRING PPI and demonstrate that the cancer-biology related functional contribution of the genes in these different neighborhood categories decreases as their distance from the CCGs increases.ResultsGenes closer to cancer genes manifest greater connectedness in the network, show greater importance in maintaining cell viability in a broad range of cancer cells in vitro, are also under greater negative germline selection pressure in the healthy populations, and have higher somatic mutation frequency and cancer effect.ConclusionsApproximately 70% of human genes are 1 or 2 steps removed from cancer genes in protein network and show functional importance in cancer-biology. These results suggest that the universe of cancer-relevant genes extends to thousands of genes that can contribute functional effects when dysregulated.
LAMP3 is critical for surfactant homeostasis in mice
Authors: Lunding Lars P. , Krause Daniel , Stichtenoth Guido , Stamme Cordula , Lauterbach Niklas , Hegermann Jan , Ochs Matthias , Schuster Björn , Sedlacek Radislav , Saftig Paul , Schwudke Dominik , Wegmann Michael , Damme Markus 
Published: February 2021

AbstractLysosome-associated membrane glycoprotein 3 (LAMP3) is a type I transmembrane protein of the LAMP protein family with a cell-type-specific expression in alveolar type II cells in mice and hitherto unknown function. In type II pneumocytes, LAMP3 is localized in lamellar bodies, secretory organelles releasing pulmonary surfactant into the extracellular space to lower surface tension at the air/liquid interface. The physiological function of LAMP3, however, remains enigmatic. We generatedLamp3knockout mice by CRISPR/Cas9. LAMP3 deficient mice are viable with an average life span and display regular lung function under basal conditions. The levels of a major hydrophobic protein component of pulmonary surfactant, SP-C, are strongly increased in the lung ofLamp3knockout mice, and the lipid composition of the bronchoalveolar lavage shows mild but significant changes, resulting in alterations in surfactant functionality. In ovalbumin-induced experimental allergic asthma, the changes in lipid composition are aggravated, and LAMP3-deficient mice exert an increased airway resistance. Our data suggest a critical role of LAMP3 in the regulation of pulmonary surfactant homeostasis and normal lung function.
waveRAPID® - a robust assay for high-throughput kinetic screens with the Creoptix® WAVEsystem
Authors: Kartal Önder , Andres Fabio , Lai May Poh , Nehme Rony , Cottier Kaspar 
Published: February 2021

AbstractSurface-based biophysical methods for measuring binding kinetics of molecular interactions, such as Surface Plasmon Resonance (SPR) or Grating-Coupled Interferometry (GCI), are now well established and widely used in drug discovery. Increasing throughput is an often-cited need in the drug discovery process, and this has been achieved with new instrument generations where multiple interactions are measured in parallel, shortening the total measurement times and enabling new application areas within the field. Here, we present the development of a novel technology called waveRAPID for a further - up to ten-fold - increase in throughput, consisting of an injection method using a single sample. Instead of sequentially injecting increasing analyte concentrations for constant durations, the analyte is injected at a single concentration in short pulses of increasing durations. A major advantage of the new method is its ability to determine kinetics from a single well of a micro-titer plate, making it uniquely suitable for kinetic screening. We present the fundamentals of this approach using a small molecule model system for experimental validation and comparing kinetic parameters to traditional methods. By varying experimental conditions, we furthermore assess the robustness of this new technique.Finally, we discuss its potential for improving hit quality and shortening cycle times in the areas of fragment screening, low molecule weight compound screening, and hit-to-lead optimization.
Sex pheromone signal and stability covary with fitness
Authors: Blankers Thomas , Lievers Rik , Plata Camila , van Wijk Michiel , van Veldhuizen Dennis , Groot Astrid T. 
Published: February 2021

ABSTRACTIf sexual signals are costly to produce or maintain, covariance between signal expression and fitness is expected. This signal-fitness covariance is important evolutionarily, because it can contribute to the maintenance of genetic variation in signal traits, despite selection from mate preferences. Chemical signals, such as moth sex pheromones, have traditionally been assumed to be stereotypical species-recognition signals, but their relationship with fitness is unclear. Here we test the hypothesis that for chemical signals that are primarily used for conspecific mate finding, there is covariation between signal properties and fitness in the noctuid mothHeliothis subflexa. Additionally, as moth signals are synthesizedde novoevery night throughout the female’s reproductive life, the maintenance of the signal can be costly. Therefore, we also hypothesized that fitness covaries with signal stability (i.e. the lack of intra-individual variation over time). We measured among- and within-individual variation in pheromone amount and composition as well as fecundity, fertility, and fitness in two independent groups of females that differed in the time in between two consecutive pheromone samples. In both groups, we found reproductive success and longevity to be correlated with pheromone amount, composition, and stability, supporting both our hypotheses. This study is the first to report a correlation between fitness and sex pheromone composition in moths, solidifying previous indications of condition-dependent moth pheromones and highlighting how signal-fitness covariance may contribute to heritable variation in chemical signals both among and within individuals.
A novel class of sulfur-containing aminolipids widespread in marine roseobacters
Authors: Smith Alastair F. , Silvano Eleonora , Päuker Orsola , Guillonneau Richard , Quareshy Mussa , Murphy Andrew , Mausz Michaela A , Stirrup Rachel , Rihtman Branko , Ferretjans Maria Aguilo , Brandsma Joost , Petersen Jörn , Scanlan David J , Chen Yin 
Published: February 2021

AbstractMarine roseobacter group bacteria are numerically abundant and ecologically important players in ocean ecosystems. These bacteria are capable of modifying their membrane lipid composition in response to environmental change. Remarkably, a variety of lipids are produced in these bacteria, including phosphorus-containing glycerophospholipids and several amino acid-containing aminolipids such as ornithine lipids and glutamine lipids. Here, we present the identification and characterization of a novelsulfur-containingaminolipid (SAL) in roseobacters. Using high resolution accurate mass spectrometry, a SAL was found in the lipid extract ofRuegeria pomeroyiDSS-3 andPhaeobacter inhibensDSM 17395. Using comparative genomics, transposon mutagenesis and targeted gene knockout, we identified a gene encoding a putative lyso-lipid acyltransferase, designatedSalA, which is essential for the biosynthesis of this SAL. Multiple sequence analysis and structural modelling suggest that SalA is a novel member of the lysophosphatidic acid acyltransferase (LPAAT) family, the prototype of which is the PlsC acyltransferase responsible for the biosynthesis of the phospholipid phosphatidic acid. SAL appears to play a key role in biofilm formation in roseobacters.SalAis widely distributed inTaraOceans metagenomes and actively expressed inTaraOceans metatranscriptomes. Our results raise the importance of sulfur-containing membrane aminolipids in marine bacteria.
An optimal growth law for RNA composition and its partial implementation through ribosomal and tRNA gene locations in bacterial genomes
Authors: Hu Xiao-Pan , Lercher Martin J. 
Published: February 2021

AbstractThe distribution of cellular resources across bacterial proteins has been quantified through phenomenological growth laws. Here, we describe a complementary bacterial growth law for RNA composition, emerging from optimal cellular resource allocation into ribosomes and ternary complexes. The predicted decline of the tRNA/rRNA ratio with growth rate agrees quantitatively with experimental data. Its regulation appears to be implemented in part through chromosomal localization, as rRNA genes are typically closer to the origin of replication than tRNA genes and thus have increasingly higher gene dosage at faster growth. At the highest growth rates inE. coli, the tRNA/rRNA ratio appears to be regulated entirely through this effect.
CD8+ T cell immunogenicity induced by endogenous EVs engineered by antigens fused to a truncated Nefmut EV-anchoring protein
Authors: Chiozzini Chiara , Manfredi Francesco , Ferrantelli Flavia , Leone Patrizia , Giovannelli Andrea , Olivetta Eleonora , Federico Maurizio 
Published: February 2021

AbstractIntramuscular injection of DNA vectors expressing the extracellular vesicle (EV)-anchoring protein Nefmut fused at its C-terminus to viral and tumor antigens elicits a potent, effective, and anti-tolerogenic CD8+ T cell immunity against the heterologous antigen. The immune response is induced through the production of EVs incorporating Nefmut-derivatives released by muscle cells. In the perspective to a possible translation into the clinic of the Nefmut-based vaccine platform, we aimed at increasing its safety profile by identifying the minimal part of Nefmut retaining the EV-anchoring protein property. We found that a C-terminal deletion of 29-amino acids did not affect the ability of Nefmut to associate with EVs. Furthermore, the EV-anchoring function was preserved when antigens from both HPV16 (i.e., E6 and E7) and SARS-CoV-2 (i.e., S1 and S2) were fused to its C-terminus. By analyzing the immune responses induced after intramuscular injection of DNA vectors expressing fusion products based on the four viral antigens, we found that the Nefmut C-terminal deletion did not impact on the levels of antigen –specific CD8+ T lymphocytes as evaluated by IFN-γ EliSpot analysis and intracellular cytokine staining. In addition, immune responses at distal sites remained unaffected, as indicated by the similar percentages of SARS-CoV-2 S1- and S2-specific CD8+ T cells detected in spleens and lung airways of mice injected with DNA vectors expressing the viral antigens fused with either Nefmut or NefmutPL.We concluded that the C-terminal Nefmut truncation does not affect stability, EV-anchoring, and CD8+ T cell immunogenicity of the fused antigen. Hence, NefmutPL represents a safer alternative to full-length Nefmut for the design of CD8+ T cell vaccines for humans.
The cryo-EM structure of vesivirus 2117 highlights functional variations in entry pathways for viruses in different clades of the Vesivirus genus
Authors: Sutherland Hazel , Conley Michaela J. , Emmott Edward , Streetley James , Goodfellow Ian G. , Bhella David 
Published: February 2021

AbstractVesivirus 2117 is an adventitious agent that has been responsible for lost productivity in biopharmaceutical production following contamination of Chinese hamster ovary cell cultures in commercial bioreactors. A member of theCaliciviridae, 2117 is classified within the Vesivirus genus in a clade that includes canine and mink caliciviruses but is distinct from the vesicular exanthema of swine clade, which includes the extensively studied feline calicivirus (FCV). We have used cryogenic electron microscopy (cryo-EM) to determine the structure of the capsid of this small, icosahedral, positive-sense RNA containing virus. We show that the outer face of the dimeric capsomeres, which contains the receptor binding site and major immunodominant epitopes in all caliciviruses studied thus far, is quite different from that of FCV. This is a consequence of a 22 amino-acid insertion in the sequence of the FCV major capsid protein that forms a ‘cantilevered arm’, which plays an important role in both receptor engagement and undergoes structural rearrangements thought to be important for genome delivery to the cytosol. Our data highlight a potentially important difference in the attachment and entry pathways employed by the different clades of the Vesivirus genus.
The glycosphingolipid inhibitor eliglustat inhibits autophagy in osteoclasts to increase bone mass and reduce myeloma bone disease
Authors: Leng Houfu , Zhang Hanlin , Li Linsen , Zhang Shuhao , Wang Yanping , Ersek Adel , Morris Emma , Sezgin Erdinc , Lee Yi-Hsuan , Li Yunsen , Mi Jianqing , Zhong Qing , Edwards Claire , Simon Anna Katharina , Horwood Nicole J. 
Published: February 2021

AbstractMultiple myeloma (MM) is a fatal hematological malignancy, where the majority of patients are diagnosed with, or develop, destructive and debilitating osteolytic bone lesions. Current treatments for MM bone disease such as the bisphosphonate zoledronic acid can result in deleterious side effects at high doses. In this study, eliglustat, an FDA approved glycosphingolipid inhibitor, was shown to reduce MM bone disease in preclinical models of MM. Mechanistically, eliglustat alters the lipid composition and plasma membrane fluidity and acts as an autophagy flux inhibitor in bone-resorbing osteoclasts (OC). Autophagic degradation of the signaling molecule TRAF3 is key step in OC differentiation; this was prevented by eliglustat in OC precursors. In addition, eliglustat works depend on TRAF3in vivo. Furthermore, the combination of eliglustat and zoledronic acid was found to have an additive effect to reduce MM bone disease, suggesting the potential for combination therapies that would allow for drug dose reductions. Taken together, this project identifies a novel mechanism in which glycosphingolipid inhibition reduces osteoclastogenesis via autophagy and highlights the translational potential of eliglustat for the treatment of bone loss disorders such as MM.One Sentence SummaryTranslational use of eliglustat as an autophagy inhibitor to limit bone lesions in multiple myeloma.
Strong transgenerational effects but no genetic adaptation in zooplankton 24 years after an abrupt +10°C climate change
Authors: Pais-Costa Antónia Juliana , Lievens Eva J. P. , Redón Stella , Sánchez Marta I. , Jabbour-Zahab Roula , Joncour Pauline , Van Hoa Nguyen , Van Stappen Gilbert , Lenormand Thomas 
Published: February 2021

AbstractThe climate is currently warming fast, threatening biodiversity all over the globe. Adaptation is often rapid when the environment changes quickly, but for climate warming very little evidence is available. Here, we investigate the pattern of adaptation to an extreme +10°C climate change in the wild, following the introduction of brine shrimpArtemia franciscanafrom San Francisco Bay, USA, to Vinh Chau saltern in Vietnam. We use a resurrection ecology approach, hatching diapause eggs from the ancestral population and the introduced population after 13 and 24 years (resp. ~54 and ~100 generations). In a series of coordinated experiments, we determined whether the introducedArtemiashow increased tolerance to higher temperatures, and the extent to which genetic adaptation, developmental plasticity, transgenerational effects, and local microbiome differences contributed to this tolerance. We find that introduced brine shrimp do show increased phenotypic tolerance to warming. Yet strikingly, these changes do not have an additive genetic component, are not caused by mitochondrial genetic variation, and are not caused by epigenetic marks set by adult parents exposed to warming. Further, we do not find any developmental plasticity in response to warming, nor any protective effect of heat-tolerant local microbiota. We conclude that the evolution of shrimp’s extreme thermal tolerance is only due to transgenerational (great)grandparental effects, possibly epigenetic marks set by parents who were exposed to high temperatures as juveniles. This finding challenges standard models of genetic and plastic adaptive responses, and our conception of how species may cope with climate warming.Significance statementAdaptation is often rapid when environments change quickly, but for climate warming little evidence is available. Many studies report no genetic responses due to pre-existing plasticity, while others point towards epigenetics and microbiota effects. In this study, we take advantage of a natural experiment to study all of these effects. We use a set of coordinated experiments and a ‘resurrection ecology’ approach, reviving resting eggs of brine shrimp up to100 generations after their introduction from a temperate to a tropical saltern. We find that heat adaptation occurs, but heritability is fully “missing”. Plasticity and microbiota play no role either, indicating that only transgenerational (great)grandmaternal effects are involved. This finding prompts us to reconsider the relative importance of the different possible mechanisms by which phenotypic change can occur, especially in response to temperature variation.
Predictive systems biomarkers of response to immune checkpoint inhibitors
Authors: Lapuente-Santana Óscar , van Genderen Maisa , Hilbers Peter , Finotello Francesca , Eduati Federica 
Published: February 2021

SUMMARYCancer cells can leverage several cell-intrinsic and -extrinsic mechanisms to escape immune system recognition. The inherent complexity of the tumor microenvironment, with its multicellular and dynamic nature, poses great challenges for the extraction of biomarkers of immune response and immunotherapy efficacy. Here, we use RNA-seq data combined with different sources of prior-knowledge to derive system-based signatures of the tumor microenvironment, quantifying immune-cell composition and intra- and inter-cellular communications. We applied multi-task learning to these signatures to predict different hallmarks of immune responses and derive cancer-type-specific models based on interpretable systems biomarkers. By applying our models to independent RNA-seq data from cancer patients treated with PD-1 inhibitors, we demonstrated that our method to Estimate Systems Immune Response (EaSIeR) accurately predicts therapeutic outcome. We anticipate that EaSIeR will be a valuable tool to provide a holistic description of immune responses in complex and dynamic systems such as tumors using available RNA-seq data.