bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geosmin suppresses defensive behaviour and elicits unusual neural responses in honey bees
Authors: Scarano Florencia , Suresh Mukilan Deivarajan , Tiraboschi Ettore , Cabirol Amélie , Nouvian Morgane , Nowotny Thomas , Haase Albrecht 
Published: October 2021

AbstractGeosmin is an odorant produced by bacteria in moist soil. It has been found to be extraordinarily relevant to some insects, but the reasons for this are not yet fully understood. Here we report the first tests of the effect of geosmin on honey bees. A stinging assay showed that the defensive behaviour elicited by the bee’s alarm pheromone is strongly suppressed by geosmin. Surprisingly, the suppression is, however, only present at very low geosmin concentrations, and completely disappears at higher concentrations. We investigated the underlying mechanisms of the behavioural change at the level of the olfactory receptor neurons by means of electroantennography and at the level of the antennal lobe output via calcium imaging. Unusual effects were observed at both levels. The responses of the olfactory receptor neurons to mixtures of geosmin and the alarm pheromone component isoamyl acetate (IAA) were lower than to pure IAA, suggesting an interaction of both compounds at the olfactory receptor level. In the antennal lobe, the neuronal representation of geosmin showed a glomerular activation that decreased with increasing concentration, correlating well with the concentration dependence of the behaviour. Computational modelling of odour transduction and odour coding in the antennal lobe suggests that a broader than usual activation of different olfactory receptor types by geosmin in combination with lateral inhibition in the antennal lobe could lead to the observed non-monotonic increasing-decreasing responses to geosmin and thus underlie the specificity of the behavioural response to low geosmin concentrations.
A Novel and Functionally Diverse Class of Acetylcholine-gated Ion Channels
Authors: Hardege Iris , Morud Julia , Courtney Amy , Schafer William R 
Published: October 2021

AbstractFast cholinergic neurotransmission is mediated by acetylcholine-gated ion channels; in particular, excitatory nicotinic acetylcholine receptors play well established roles in virtually all nervous systems. Acetylcholine-gated inhibitory channels have also been identified in some invertebrate phyla, yet their roles in the nervous system are less well understood. We report the existence of multiple new inhibitory acetylcholine-gated ion channels with diverse ligand binding properties in C. elegans. We identify three channels, LGC-40, LGC-57 and LGC-58, whose primary ligand is choline rather than acetylcholine, as well as the first evidence of a truly polymodal channel, LGC-39, which is activated by both cholinergic and aminergic ligands. Using our newly deorphanised channel evidence we uncover the surprising extent to which a single neuron expresses both excitatory and inhibitory channels, not only for acetylcholine but also the other major neurotransmitters. The results presented in this study offer a new insight into the potential evolutionary benefit of a vast and diverse repertoire of LGICs to generate complexity in an anatomically compact nervous system.
Genetic determinants of antibiotic resistance and the evolution of trade-offs during adaptation in a single patient
Authors: Woods Robert J. , Barbosa Camilo , Koepping Laura , Raygoza Garay Juan A. , Mwangi Michael , Read Andrew F. 
Published: October 2021

AbstractThe processes by which pathogens evolve within single hosts dictate the efficacy of treatment strategies designed to slow antibiotic resistance evolution and influence the population-wide resistance levels. The aim of this study is to describe the underlying genetic and phenotypic changes leading to antibiotic resistance within a single patient who died as resistance evolved to available antibiotics. We assess whether robust patterns of collateral sensitivity and response to combinations exist that might have been leveraged to improve therapy. Whole-genome sequencing was completed for nine isolates taken from this patient over 279 days of chronic infection withEnterobacter hormaechei, along with systematic measurements of changes in resistance against five of the most relevant drugs considered for treatment. The entirety of the genetic change is consistent withde novomutations and plasmid loss events, without the acquisition of foreign genetic material via horizontal gene transfer. The isolates formed three genetically distinct lineages, with early evolutionary trajectories being supplanted by previously unobserved multi-step evolutionary trajectories. Importantly, no single isolate evolved resistance to all of the antibiotics considered for treatment againstE. hormaechei(i.e., none was pan-resistant). Patterns of collateral sensitivity and response to combination therapy revealed contrasting patterns across this diversifying population. Translating antibiotic resistance management strategies from theoretical and laboratory data to clinical situations, such as this, may require managing diverse populations with unpredictable resistance trajectories.
Developmental cell death of cortical projection neurons is controlled by a Bcl11a/Bcl6-dependent pathway
Authors: Wiegreffe C. , Wahl T. , Joos N. S. , Bonnefont J. , Vanderhaeghen P. , Liu P. , Britsch S. 
Published: October 2021

AbstractDevelopmental neuron death plays a pivotal role in refining organization and wiring during neocortex formation. Aberrant regulation of this process results in neurodevelopmental disorders including impaired learning and memory. Underlying molecular pathways are incompletely determined. Loss of Bcl11a in cortical projection neurons induces pronounced cell death in upper-layer cortical projection neurons during postnatal corticogenesis. We used this genetic model to explore genetic mechanisms by which developmental neuron death is controlled. Unexpectedly, we found Bcl6, previously shown to be involved in transition of cortical neurons from progenitor to postmitotic differentiation state to provide a major check point regulating neuron survival during late cortical development. We show that Bcl11a is a direct transcriptional regulator of Bcl6. Deletion of Bcl6 exerts death of cortical projection neurons. In turn, reintroduction of Bcl6 into Bcl11a mutants prevents induction of cell death in these neurons. Together, our data identify a novel Bcl11a/Bcl6-dependent molecular pathway in regulation of developmental cell death during corticogenesis.
Travelling wave and asymptotic analysis of a multiphase moving boundary model for engineered tissue growth
Authors: Jepson Jacob M. , Fadai Nabil T. , O’Dea Reuben D. 
Published: October 2021

AbstractWe derive a multiphase, moving boundary model to represent the development of tissue in vitro in a porous tissue engineering scaffold. We consider a cell, extra-cellular liquid and a rigid scaffold phase, and adopt Darcy’s law to relate the velocity of the cell and liquid phases to their respective pressures. Cell-cell and cell-scaffold interactions which can drive cellular motion are accounted for by utilising relevant constitutive assumptions for the pressure in the cell phase. We reduce the model to a nonlinear reaction-diffusion equation for the cell phase, coupled to a moving boundary condition for the tissue edge, the diffusivity being dependent on the cell and scaffold volume fractions, cell and liquid viscosities, and parameters that relate to cellular motion. Numerical simulations reveal that the reduced model admits three regimes for the evolution of the tissue edge at large-time: linear, logarithmic and stationary. Employing travelling wave and asymptotic analysis, we characterise these regimes in terms of parameters related to cellular production and motion. The results of our investigation allow us to suggest optimal values for the governing parameters, so as to stimulate tissue growth in an engineering scaffold.
Inter-species microbiota transplantation recapitulates microbial acquisition and persistence in mosquitoes
Authors: Coon Kerri L. , Hegde Shivanand , Hughes Grant L. 
Published: October 2021

AbstractBackgroundMosquitoes harbor microbial communities that play important roles in their growth, survival, reproduction, and ability to transmit human pathogens. Microbiome transplantation approaches are often used to study host-microbe interactions and identify microbial taxa and assemblages associated with health or disease. However, no such approaches have been developed to manipulate the microbiota of mosquitoes.ResultsHere, we developed an approach to transfer entire microbial communities between mosquito cohorts. We undertook transfers between (Culex quinquefasciatustoAedes aegypti)and within (Ae. aegypti to Ae. aegypti) species to validate the approach and determine the number of mosquitoes required to prepare donor microbiota. After the transfer, we monitored mosquito development and microbiota dynamics throughout the life cycle. Typical holometabolous lifestyle-related microbiota structures were observed, with higher dynamics of microbial structures in larval stages, including the larval water, and less diversity in adults. Microbiota diversity in recipient adults was also more similar to the microbiota diversity in donor adults.ConclusionsThis study provides the first evidence for successful microbiome transplantation in mosquitoes. Our results highlight the value of such methods for studying mosquito-microbe interactions and lay the foundation for future studies to elucidate the factors underlying microbiota acquisition, assembly, and function in mosquitoes under controlled conditions.
Progesterone supplementation in mice leads to microbiome alterations and weight gain in a sex-specific manner
Authors: Nuriel-Ohayon Meital , Belogovski Anna , Komissarov Sharon , Izhak Meirav Ben , Shtossel Oshrit , Neuman Hadar , Ziv Oren , Turjeman Sondra , Bel Shai , Louzoun Yoram , Koren Omry 
Published: October 2021

AbstractBackgroundProgesterone is a steroid hormone produced by the ovaries, involved in pregnancy progression and necessary for successful gestation. We have previously shown that progesterone affects gut microbiota composition and leads to increased relative abundance of Bifidobacterium.ResultsIn non-pregnant female GF mice, levels of progesterone were significantly higher than in SPF mice of the same status. However, no significant differences were observed between GF and SPF males. Females treated with progesterone gained more weight than females treated with a placebo. In contrast to female mice, males treated with progesterone did not gain significantly more weight than males treated with a placebo. Progesterone supplementation led to microbial changes in females but not in males (16S rRNA sequencing). Accordingly, the weight gain observed in female mice treated with progesterone was fully transferable to both male and female germ-free mice via fecal transplantation.ConclusionsWe demonstrate that bacteria play a role in regulating progesterone levels in a female-specific manner. Furthermore, weight gain and metabolic changes associated with progesterone may be mediated by the gut microbiota.
SynTracker: a synteny based tool for tracking microbial strains
Authors: Enav Hagay , Ley Ruth E. 
Published: October 2021

AbstractIn the human gut microbiome, specific strains emerge due to within-host evolution and can occasionally be transferred to or from other hosts. Phenotypic variance among such strains can have implications for strain transmission and interaction with the host. Surveilling strains of the same species, within and between individuals, can further our knowledge about the way in which microbial diversity is generated and maintained in host populations. Existing methods to estimate the biological relatedness of similar strains usually rely on either detection of single nucleotide polymorphisms (SNP), which may include sequencing errors, or on the analysis of pangenomes, which can be limited by the requirement for extensive gene databases. To complement existing methods, we developed SynTracker. This strain-comparison tool is based on synteny comparisons between strains, or the comparison of the arrangement of sequence blocks in two homologous genomic regions in pairs of metagenomic assemblies or genomes. Our method is executed in a species-specific manner, has a low sensitivity to SNPs, does not require a pre-existing database, and can correctly resolve strains using complete or draft genomes and metagenomic samples using <5% of the genome length. When applied to metagenomic datasets, we detected person-specific strains with an average sensitivity of 97% and specificity of 99%, and strain-sharing events in mother-infant pairs. SynTracker can be used to study the population structure of specific microbial species between and within environments, to identify evolutionary trajectories in longitudinal datasets, and to further understanding of strain sharing networks.
A systematic genotype-phenotype map for missense variants in the human intellectual disability-associated geneGDI1
Authors: Silverstein Rachel A. , Sun Song , Verby Marta , Weile Jochen , Wu Yingzhou , Gebbia Marinella , Fotiadou Iosifina , Kitaygorodsky Julia , Roth Frederick P. 
Published: October 2021

AbstractNext generation sequencing has become a common tool in the diagnosis of genetic diseases. However, for the vast majority of genetic variants that are discovered, a clinical interpretation is not available. Variant effect mapping allows the functional effects of many single amino acid variants to be characterized in parallel. Here, we combine multiplexed functional assays with machine learning to assess the effects of amino acid substitutions in the human intellectual disability-associated gene,GDI1. We show that the resulting variant effect map can be used to discriminate pathogenic from benign variants. Our variant effect map recovers known biochemical and structural features ofGDI1and reveals additional aspects ofGDI1function. We explore how our functional assays can aid in the interpretation of novelGDI1variants as they are discovered, and to re-classify previously observed variants of unknown significance.
Membrane-assisted assembly and selective autophagy of enteroviruses
Authors: Dahmane Selma , Kerviel Adeline , Morado Dustin R. , Shankar Kasturika , Ahlman Björn , Lazarou Michael , Altan-Bonnet Nihal , Carlson Lars-Anders 
Published: October 2021

AbstractEnteroviruses are non-enveloped positive-sense RNA viruses that cause diverse diseases in humans. Their rapid multiplication depends on remodeling of cytoplasmic membranes for viral genome replication. It is unknown how virions assemble around these newly synthesized genomes and how they are then loaded into autophagic membranes for release through secretory autophagy. Here, we use cryo-electron tomography of infected cells to show that poliovirus assembles directly on replication membranes. Pharmacological untethering of capsids from membranes abrogates RNA encapsidation. Our data directly visualize a membrane-bound half-capsid as a prominent virion assembly intermediate. Assembly progression past this intermediate depends on the class III phosphatidylinositol 3-kinase VPS34, a key host-cell autophagy factor. On the other hand, the canonical autophagy initiator ULK1 is shown to restrict virion production since its inhibition leads to increased accumulation of virions in vast intracellular arrays, followed by an increased vesicular release at later time points. Finally, we identify multiple layers of selectivity in virus-induced autophagy, with a strong selection for RNA-loaded virions over empty capsids and the segregation of virions from other types of autophagosome contents. These findings provide an integrated structural framework for multiple stages of the poliovirus life cycle.
Structure of the stress-related LHCSR1 complex determined by an integrated computational strategy
Authors: Prandi Ingrid Guarnetti , Sláma Vladislav , Pecorilla Cristina , Cupellini Lorenzo , Mennucci Benedetta 
Published: October 2021

AbstractLight-harvesting complexes (LHCs) are pigment-protein complexes whose main function is to capture sunlight and transfer the energy to reaction centers of photosystems. In response to varying light conditions, LH complexes also play photoregulation and photoprotection roles. In algae and mosses, a sub-family of LHCs, Light-Harvesting complex stress related (LHCSR), is responsible for photoprotective quenching. Despite their functional and evolutionary importance, no direct structural information on LHCSRs is available that can explain their unique properties. In this work we propose a structural model of LHCSR1 from the moss P. Patens, obtained through an integrated computational strategy that combines homology modeling, molecular dynamics, and multiscale quantum chemical calculations. The model is validated by reproducing the spectral properties of LHCSR1. Our model reveals the structural specificity of LHCSR1, as compared with the CP29 LH complex, and poses the basis for understanding photoprotective quenching in mosses.
Tracking the fates of iron-labeled tumor cells in vivo using Magnetic Particle Imaging
Authors: Makela Ashley V. , Schott Melissa A. , Sehl Olivia C. , Gevaert Julia J. , Foster Paula J. , Contag Christopher H. 
Published: October 2021

ABSTRACTThe use of imaging to detect and monitor the movement and accumulation of cells in living subjects can provide significant insights that can improve our understanding of metastasis and guide therapeutic development. For cell tracking using Magnetic Resonance Imaging (MRI), cells are labeled with iron oxides and the effects of the iron on water provides contrast. However, due to low specificity and difficulties in quantification with MRI, other modalities and approaches need to be developed. Magnetic Particle Imaging (MPI) is an emerging imaging technique which directly detects magnetic iron, allowing for a specific, quantitative and sensitive readout. Here, we use MPI to image iron-labeled tumor cells longitudinally, from implantation and growth at a primary site to movement to distant anatomic sites. In vivo bioluminescent imaging (BLI) was used to localize tumor metastases and computed tomography (CT) allowed for correlation of these signals to anatomic locations. These three imaging modalities provide information on immune escape and metastasis of iron-labeled, and unlabeled, tumor cells, and the accumulation of cell-free iron contrast over time. We identified iron signals by MPI and tumor cells via BLI, and correlated these positive contrast images with CT scans to reveal the anatomic sites with cancer cells; histologic analysis confirmed the presence of iron-labeled tumor cells in the tissues, suggesting that the metastatic cells retained enough iron for MPI detection. The use of multi-modality cell tracking reveals the movement, accumulation and fates of labeled cells that will be helpful understanding cancer progression and guiding the development of targeted therapies.
NN-RNALoc: neural network-based model for prediction of mRNA sub-cellular localization using distance-based sub-sequence profiles
Authors: Babaiha Negin Sadat , Aghdam Rosa , Eslahchi Changiz 
Published: October 2021

AbstractLocalization of messenger RNAs (mRNA) as a widely observed phenomenon is considered as an efficient way to target proteins to a specific region of a cell and is also known as a strategy for gene regulation. The importance of correct intracellular RNA placement in the development of embryonic and neural dendrites has long been demonstrated in former studies. Improper localization of RNA in the cell, which has been shown to occur due to a variety of reasons, including mutations in trans-regulatory elements, is also associated with the occurrence of some neuromuscular diseases as well as cancer. We propose NN-RNALoc, a neural network-based model to predict the cellular location of mRNAs. The features extracted from mRNA sequences along with the information gathered from their proteins are fed to this prediction model. We introduce a novel distance-based sub-sequence profile for representation of RNA sequences which is more memory and time efficient and comparying to the k-mer frequencies, can possibly better encode sequences when the distance k increases. The performance of NN-RNALoc on the following benchmark datsets CeFra-seq and RNALocate, is compared to the results achieved by two powerful prediction models that were proposed in former studies named as mRNALoc and RNATracker The results reveal that the employment of protein-protein interaction information, which plays a crucial role in many biological functions, together with the novel distance-based sub-sequence profiles of mRNA sequences, leads to a more accurate prediction model. Besides, NN-RNALoc significantly reduces the required computing time compared to previous studies. Source code and data used in this study are available at: https://github.com/NeginBabaiha/NN-RNALoc
Disruption of nucleoid expanded conformation by toxic aberrant proteins synthesized in Escherichia coli
Authors: Tawde Mangala , Bior Abdelaziz , Feiss Michael , Freimuth Paul 
Published: October 2021

AbstractAminoglycoside antibiotics interfere with selection of cognate tRNAs during translation, resulting in the production of aberrant proteins that are the ultimate cause of the antibiotic bactericidal effect. To determine if these aberrant proteins are recognized as substrates by the cell’s protein quality control machinery, we studied whether the heat shock (HS) response was activated following exposure of Escherichia coli to the aminoglycoside kanamycin (Kan). Levels of the HS transcription factor σ32 increased about 10-fold after exposure to Kan, indicating that at least some aberrant proteins were recognized as substrates by the molecular chaperone DnaK. To investigate whether toxic aberrant proteins therefore might escape detection by the QC machinery, we studied model aberrant proteins that had a bactericidal effect when expressed in E. coli from cloned genes. As occurred following exposure to Kan, levels of σ32 were permanently elevated following expression of an acutely toxic 48-residue protein (ARF48), indicating that toxic activity and recognition by the QC machinery are not mutually exclusive properties of aberrant proteins, and that the HS response was blocked in these cells at some step downstream of σ32 stabilization. This block could result from halting of protein synthesis or from radial condensation of nucleoids, both of which occurred rapidly following ARF48 induction. Nucleoids were similarly condensed following expression of toxic aberrant secretory proteins, suggesting that transertion of inner membrane proteins, a process that expands nucleoids into an open conformation that promotes growth and gene expression, was disrupted in these cells. The 48-residue ARF48 protein would be well-suited for structural studies to further investigate the toxic mechanism of aberrant proteins.