bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sema3A Facilitates a Retrograde Death Signal via CRMP4-Dynein Complex Formation in ALS Motor Axons
Authors: Maimon Roy , Ankol Lior , Weissova Romana , Tank Elizabeth , Pery Tal Gradus , Opatowsky Yarden , Barmada Sami , Balastik Martin , Perlson Eran 
Published: September 2019

AbstractAmyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease with selective dysfunction; it causes the death of motor neurons (MNs). In spite of some progress, currently no effective treatment is available for ALS. Before such treatment can be developed, a more thorough understanding of ALS pathogenesis is required. Recently, we demonstrated that ALS-mutated muscles contribute to ALS pathology via secretion of destabilizing factors such as Sema3A; these factors trigger axon degeneration and Neuromuscular Junction (NMJ) disruption. Here, we focus on the molecular mechanism by which muscle contribute to MNs loss in ALS. We identified CRMP4 as part of a retrograde death signal generated in response to muscle-secreted Sema3A, in ALS-diseased MNs. Exposing distal axons to Sema3A induces CRMP4-dynein complex formation and MN loss in both mouse (SOD1G93A) and human-derived (C9orf72) ALS models. Introducing peptides that interfere with CRMP4-dynein interaction in MN axons profoundly reduces Sema3A-dependent MN loss. Thus, we discovered a novel retrograde death signal mechanism underlying MN loss in ALS.SummaryMaimon et al. identify a novel retrograde death mechanism that contribute to MN loss in ALS, in which CRMP4-Dynein complex is form and retrogradely move along the axon.
Size matters, so does condition: the use of a body condition index reveals the costs and benefits of structural body size in an insect
Authors: Zanchi Caroline , Moret Yannick , Gillingham Mark A. F. 
Published: September 2019

AbstractInsects are core actors for the balance of many earth ecosystems, as well as an alternative source of food and feed with a low ecological footprint. A comprehensive understanding of their life history requires reliable tools. Body condition constitutes the amount of energy reserves available to a fitness trait after maintenance costs have been accounted for. Body condition is standardly estimated using Body Condition Indexes (BCIs) in vertebrates. In insects the relevance of BCIs is frequently questioned on the basis that they might not accurately reflect neither energy reserves nor fitness.. However, to date no study has tested whether the very concept of body condition is relevant in insects, i.e. whether BCIs accurately reflect the relative energy reserves allocated to fitness traits.We propose that the relevance of using BCIs in insects depends on whether their structural size has a fitness cost. If on the contrary insects only benefit from a larger body size, a simple measurement of body size or mass will predict fitness, but not a BCI. We experimentally manipulated food availability at the larval and adult stage and used total fecundity of females as a fitness proxy of Tenebrio molitor, an important model in physiology, ecology and evolution, and one of the first insects to be considered as a source of food and feed.Our results support three key assumptions of the relevance of BCIs in insects: (i) a valid BCI correlated with energy reserves corrected for a given size (i.e. relative energy reserves) and not with absolute measures of energy reserves; (ii) both structural size and body condition positively predict different components of fitness; and, (iii) the effect of body condition was dependent on resource availability, whereby its effect was only apparent and large when food was unrestricted at the larval stage and restricted at the adult stage.Overall we demonstrate the relevance of using BCIs in insects. Their use should be generalized to improve fitness readouts in evolution, ecological and physiological studies, as well as improve their husbandry for commercial purposes.
Seeing β-arrestin in action: The role of β-arrestins in Histamine 1 Receptor signaling
Authors: Pietraszewska-Bogiel A , Goedhart J 
Published: September 2019

ABSTRACTß-arrestins regulate G protein-coupled receptor functions by influencing their signaling activity and intracellular location. Histamine is a major chemical mediator of allergic reactions, and its action is mainly mediated by the Gq/11- and Gi-coupled H1R. Contrary to accumulating insights into G protein-mediated signaling downstream of H1R, very little is known about the function of ß-arrestins in H1R signaling. Here, we describe dynamic, live cell measurements of ß-arrestin recruitment upon H1R activation in HEK293TN cells. Our observations classify H1R as a class A receptor, undergoing transient interactions with ß-arrestin. To investigate the relative contributions of G proteins and ß-arrestins to H1R signaling, we use specific G protein inhibitors, as well as ß-arrestin overexpression and depletion, and quantify various signaling outcomes in a panel of dynamic, live cell biosensor assays. Overall, we link ß-arrestins to desensitization of H1R-mediated signaling and show that ERK activation downstream of endogenous (HeLa, HUVEC) or transiently expressed (HEK293TN) H1R is largely Gq-mediated.
Are trade-offs between flexibility and efficiency in systematic conservation planning avoidable ?
Authors: Drira Sabrine , Lasram Frida Ben Rais , Hattab Tarek , Shin Yunne Jai , Jenhani Amel Ben Rejeb , Guilhaumon François 
Published: September 2019

AbstractSpecies distribution models (SDMs) have been proposed as a way to provide robust inference about species-specific sites suitabilities, and have been increasingly used in systematic conservation planning (SCP) applications. However, despite the fact that the use of SDMs in SCP may raise some potential issues, conservation studies have overlooked to assess the implications of SDMs uncertainties. The integration of these uncertainties in conservation solutions requires the development of a reserve-selection approach based on a suitable optimization algorithm. A large body of research has shown that exact optimization algorithms give very precise control over the gap to optimality of conservation solutions. However, their major shortcoming is that they generate a single binary and indivisible solution. Therefore, they provide no flexibility in the implementation of conservation solutions by stakeholders. On the other hand, heuristic decision-support systems provide large amounts of sub-optimal solutions, and therefore more flexibility. This flexibility arises from the availability of many alternative and sub-optimal conservation solutions. The two principles of efficiency and flexibility are implicitly linked in conservation applications, with the most mathematically efficient solutions being inflexible and the flexible solutions provided by heuristics suffering sub-optimality. In order to avoid the trade-offs between flexibility and efficiency in systematic conservation planning, we propose in this paper a new reserve-selection framework based on mathematical programming optimization combined with a post-selection of SDM outputs. This approach leads to a reserve-selection framework that might provide flexibility while simultaneously addressing efficiency and representativeness of conservation solutions and the adequacy of conservation targets. To exemplify the approach we a nalyzed an experimental design crossing pre- and post-selection of SDM outputs versus heuristics and exact mathematical optimizations. We used the Mediterranean Sea as a biogeographical template for our analyses, integrating the outputs of 8 SDM techniques for 438 fishes species.
Coordination of transcriptional and translational regulations in human epithelial cells infected by Listeria monocytogenes
Authors: Besic Vinko , Habibolahi Fatemeh , Noël Benoît , Rupp Sebastian , Genovesio Auguste , Lebreton Alice 
Published: September 2019

AbstractThe invasion of mammalian cells by intracellular bacterial pathogens reshuffles their gene expression and functions; however, we lack dynamic insight into the distinct control levels that shape the host response. Here, we have addressed the respective contribution of transcriptional and translational regulations during a timecourse of infection of human intestinal epithelial cells by an epidemic strain of Listeria monocytogenes, using transcriptome analysis paralleled with ribosome profiling. Upregulations were dominated by early transcriptional activation of pro-inflammatory genes, whereas translation inhibition appeared as the major driver of downregulations. Instead of a widespread but transient shutoff, translation inhibition affected specifically and durably transcripts encoding components of the translation machinery harbouring a 5’-terminal oligopyrimidine motif. Pre-silencing the most repressed target gene (PABPC1) slowed down the intracellular multiplication of Listeria monocytogenes, suggesting that the infected host cell can benefit from the repression of genes involved in protein synthesis and thereby better control infection.
Crossmodal Pattern Discrimination in Humans and Robots: A Visuo-Tactile Case Study
Authors: Higgen Focko L. , Ruppel Philipp , Görner Michael , Kerzel Matthias , Hendrich Norman , Feldheim Jan , Wermter Stefan , Zhang Jianwei , Gerloff Christian 
Published: September 2019

AbstractThe quality of crossmodal perception hinges on two factors: The accuracy of the independent unimodal perception and the ability to integrate information from different sensory systems. In humans, the ability for cognitively demanding crossmodal perception diminishes from young to old age.To research to which degree impediments of these two abilities contribute to the age-related decline and to evaluate how this might apply to artificial systems, we replicate a medical study on visuo-tactile crossmodal pattern discrimination utilizing state-of-the-art tactile sensing technology and artificial neural networks. We explore the perception of each modality in isolation as well as the crossmodal integration.We show that in an artificial system the integration of complex high-level unimodal features outperforms the comparison of independent unimodal classifications at low stimulus intensities where errors frequently occur. In comparison to humans, the artificial system outperforms older participants in the unimodal as well as the crossmodal condition. However, compared to younger participants, the artificial system performs worse at low stimulus intensities. Younger participants seem to employ more efficient crossmodal integration mechanisms than modelled in the proposed artificial neural networks.Our work creates a bridge between neurological research and embodied artificial neurocognitive systems and demonstrates how collaborative research might help to derive hypotheses from the allied field. Our results indicate that empirically-derived neurocognitive models can inform the design of future neurocomputational architectures. For crossmodal processing, sensory integration on lower hierarchical levels, as suggested for efficient processing in the human brain, seems to improve the performance of artificial neural networks.
Differential equation based minimal model describing metabolic oscillations inBacillus subtilisbiofilms
Authors: Garde Ravindra , Ibrahim Bashar , Kovács Ákos T. , Schuster Stefan 
Published: September 2019

AbstractBiofilms offer an excellent example of ecological interaction among bacteria. Temporal and spatial oscillations in biofilms are an emerging topic. In this paper we describe the metabolic oscillations inBacillus subtilisbiofilms by applying the smallest theoretical chemical reaction system showing Hopf bifurcation proposed by Wilhelm and Heinrich in 1995. The system involves three differential equations and a single bilinear term. We perform computer simulations and a detailed analysis of the system including bifurcation analysis and quasi-steady-state approximation. We also discuss the feedback structure of the system and the correspondence of the simulations to biological observations. We also specifically select parameters that are more suitable for the biological scenario of biofilm oscillations. Our theoretical work suggests potential scenarios about the oscillatory behaviour of biofilms and also serves as an application of a previously described chemical oscillator to a biological system.
How the dual PDZ domain from Postsynaptic density protein 95 clusters ion channels and receptors
Authors: Rodzli Nazahiyah Ahmad , Lockhart-Cairns Michael , Levy Colin W. , Chipperfield John , Bird Louise , Baldock Clair , Prince Stephen M. 
Published: September 2019

AbstractPSD-95 is a member of Membrane Associated Guanylate Kinase class of proteins which form scaffolding interactions with partner proteins including ion and receptor channels. PSD-95 is directly implicated in modulating the electrical responses of excitable cells. The first two PSD-95/Disks Large/Zona Occludens domains of PSD-95 have been shown to be the key component in the formation of channel clusters. We report crystal structures of the dual domain in both in apo and ligand-bound form; thermodynamic analysis of ligand association and Small Angle X-ray Scattering of the dual domain in the absence and presence of ligands. These experiments reveal that the ligated double domain forms a scaffold in the complete sense of the word. The concentration of the components in this study is comparable to those found in compartments of excitable cells such as the postsynaptic density and juxta-paranodes of Ranvier. The properties of the dual domain explain the basis of the scaffolding function of PSD-95, and provide a more detailed understanding of the integration of key components of neuronal specializations involved in nervous signal transmission.
Fly-QMA: Automated analysis of mosaic imaginal discs inDrosophila
Authors: Bernasek Sebastian , Peláez Nicolás , Carthew Richard , Bagheri Neda , Amaral Luís 
Published: September 2019

AbstractMosaic analysis provides a means to probe developmental processes in situ by generating loss-of-function mutants within otherwise wildtype tissues. Combining these techniques with quantitative microscopy enables researchers to rigorously compare RNA or protein expression across the resultant clones. However, visual inspection of mosaic tissues remains common in the literature because quantification demands considerable labor and computational expertise. Practitioners must segment cell membranes or cell nuclei from a tissue and annotate the clones before their data are suitable for analysis. Here, we introduce Fly-QMA, a computational framework that automates each of these tasks for confocal microscopy images ofDrosophilaimaginal discs. The framework includes an unsupervised annotation algorithm that incorporates spatial context to inform the genetic identity of each cell. We use a combination of real and synthetic validation data to survey the performance of the annotation algorithm across a broad range of conditions. By contributing our framework to the open-source software ecosystem, we aim to contribute to the current move toward automated quantitative analysis among developmental biologists.Author summaryBiologists use mosaic tissues to compare the behavior of genetically distinct cells within an otherwise equivalent context. The ensuing analysis is often limited to qualitative insight. However, it is becoming clear that quantitative models are needed to unravel the complexities of many biological systems. In this manuscript we introduce Fly-QMA, an open-source software framework that automates the quantification of mosaic analysis for Drosophila imaginal discs, a common setting for studies of developmental processes. The software automatically extracts quantitative measurements from confocal images of mosaic tissues, rectifies any cross-talk between fluorescent reporters, and identifies clonally-related subpopulations of cells. Together, these functions allow users to rigorously ascribe changes in gene expression to the presence or absence of particular genes. We validate the performance of our framework using both real and synthetic data. Through its publication, we aim to contribute to the current move toward automated quantitative analysis among biologists.
Establishment ofWolbachiastrainwAlbB in Malaysian populations ofAedes aegyptifor dengue control
Authors: Nazni W. A. , Hoffmann A. A. , Noor Afizah A. , Cheong Y. L. , Mancini M. V. , Golding N. , Kamarul M. R. G. , Arif A. K. M. , Thohir H. , Nur Syamimi H. S. , Nur Zatil Aqmar M. Z. , Nur Ruqqayah M. M. , Siti Nor Syazwani A. , Faiz A. , Irfan M. N. F. R. , Rubaaini S. , Nuradila N. , Nizam M. M. N. , Mohamad Irwan M. S. , Endersby-Harshman N. M. , White V. L. , Ant T. H. , Herd C. , Hasnor H. A. , Abu Bakar R. , Hapsah M. D. , Khadijah K. , Kamilan D. , Lee S. C. , Paid M. , Fadzilah K. , Gill B. S. , Lee H. L. , Sinkins S. P. 
Published: September 2019

AbstractDengue has enormous health impacts globally. A novel approach to decrease dengue incidence involves the introduction ofWolbachiaendosymbionts that block dengue virus transmission into populations of the primary vector mosquito,Aedes aegypti. ThewMelWolbachiastrain has previously been trialed in open releases ofAe. aegypti; however thewAlbB strain has been shown to maintain higher density thanwMel at high larval rearing temperatures. Releases ofAe. aegyptimosquitoes carryingwAlbB were carried out in 6 diverse sites in greater Kuala Lumpur, Malaysia, with high endemic dengue transmission. The strain was successfully established and maintained at very high population frequency at some sites, or persisted with additional releases following fluctuations at other sites. Based on passive case monitoring, reduced human dengue incidence was observed in the release sites when compared to control sites. ThewAlbB strain ofWolbachiaprovides a promising option as a tool for dengue control, particularly in very hot climates.
A unique mode of nucleic acid immunity performed by a single multifunctional enzyme
Authors: Bari S. M. Nayeemul , Chou-Zheng Lucy , Howell Olivia , Cater Katie , Dandu Vidya Sree , Thomas Alexander , Aslan Barbaros , Hatoum-Aslan Asma 
Published: September 2019

AbstractThe perpetual arms race between bacteria and their viruses (phages) has given rise to diverse immune systems, including restriction-modification and CRISPR-Cas, which sense and degrade phage-derived nucleic acids. These complex systems rely upon production and maintenance of multiple components to achieve anti-phage defense. However, the prevalence and effectiveness of much simpler, single-component systems that cleave DNA remain unknown. Here, we describe a novel mode of nucleic acid immunity performed by a single enzyme with nuclease and helicase activities, herein referred to as Nhi. This enzyme provides robust protection against diverse staphylococcal phages and prevents phage DNA accumulation in cells stripped of all other known defenses. Our observations support a model in which Nhi acts as both the sensor and effector to degrade phage-specific replication intermediates.Importantly, Nhi homologs are distributed in diverse bacteria and exhibit functional conservation, highlighting the versatility of such compact weapons as major players in anti-phage defense.
Voluntary motor commands are preferentially released during restricted sensorimotor beta rhythm phases
Authors: Hussain Sara J , Vollmer Mary K , Iturrate Iñaki , Quentin Romain 
Published: September 2019

AbstractVoluntary movement requires motor commands to be released from motor cortex (M1) and transmitted to spinal motoneurons and effector muscles. M1 activity oscillates between brief excitatory and inhibitory states that correlate with single neuron spiking rates. Here, we asked if the motor commands needed to produce voluntary, self-paced finger movements are preferentially released from M1 during restricted phases of this ongoing sensorimotor oscillatory activity. 21 healthy adults performed a self-paced finger movement task while EEG and EMG signals were recorded. For each finger movement, we identified the individual sensorimotor mu (8-12 Hz) and beta (13-35 Hz) oscillatory phase at the estimated time of motor command release from M1 by subtracting individually-defined MEP latencies from EMG-determined movement onset times. We report that motor commands were preferentially released at ~120° along the beta cycle but were released uniformly across the mu cycle. These results suggest that motor commands are preferentially released from M1 near optimal peak phases of endogenous beta rhythms.
Pancreatic cancer cells assemble a CXCL12-keratin 19 coating to resist immunotherapy
Authors: Wang Zhikai , Yan Ran , Li Jiayun , Gao Ya , Moresco Philip , Yao Min , Hechtman Jaclyn F. , Weiss Matthew J. , Janowitz Tobias , Fearon Douglas T. 
Published: September 2019

AbstractHow pancreatic ductal adenocarcinoma (PDA) cells stimulate CXCR4 to exclude T cells and resist T cell checkpoint inhibitors is not known. Here, we find that CXCL12, the ligand for CXCR4 that is produced by the cancer-associated fibroblast, “coats” human PDA and colorectal cancer cells as covalent heterodimers with keratin 19 (KRT19). Modeling the formation of the heterodimer with three proteins shows that KRT19 binds CXCL12 and transglutaminase-2 (TGM2), and that TGM2 converts the reversible KRT19-CXCL12 complex into a covalent heterodimer. We validate this model by showing that cancer cells in mouse PDA tumors must express KRT19 and TGM2 to become coated with CXCL12, exclude T cells, and resist immunotherapy with anti-PD-1 antibody. Thus, PDA cells have a cell-autonomous means by which they capture CXCL12 to mediate immune suppression, which is potentially amenable to therapy.One Sentence SummaryCancer cells in pancreatic ductal adenocarcinoma use transglutaminase-2 to assemble a coating comprised of covalent CXCL12-keratin 19 heterodimers that excludes T cells and mediates resistance to inhibition of the PD-1 T cell checkpoint.
Effects of social defeat stress and fluoxetine treatment on neurogenesis and behaviour in mice that lack zinc transporter 3 (ZnT3) and vesicular zinc
Authors: McAllister Brendan B. , Pochakom Angela , Fu Selena , Dyck Richard H. 
Published: September 2019

ABSTRACTDepression is a leading cause of disability worldwide, in part because the available treatments are inadequate and do not work for many people. The neurobiology of depression, and the mechanism of action of common antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs), is not well understood. One mechanism thought to underlie the effects of these drugs is upregulation of adult hippocampal neurogenesis. Evidence indicates that vesicular zinc is required for modulation of adult hippocampal neurogenesis, at least under some circumstances. Vesicular zinc refers to zinc that is stored in the synaptic vesicles of certain neurons, including in the hippocampus, and released in response to neuronal activity. It can be eliminated from the brain by deletion of zinc transporter 3 (ZnT3), as is the case in ZnT3 knockout mice. Here, we examined the effects of repeated social defeat stress and subsequent chronic treatment with the SSRI fluoxetine on behaviour and neurogenesis in ZnT3 knockout mice. We hypothesized that fluoxetine treatment would increase neurogenesis and reverse stress-induced behavioural symptoms in wild type, but not ZnT3 knockout, mice. As anticipated, stress induced persistent depression-like effects, including social avoidance and anxiety-like behaviour. Fluoxetine decreased social avoidance, though the effect was not specific to the stressed mice, but did not affect anxiety-like behaviour. Surprisingly, stress increased the survival of neurons born 1 day after the last episode of defeat stress. Fluoxetine treatment also increased cell survival, particularly in wild type mice, though it did not affect proliferation. Our results did not support our hypothesis that vesicular zinc is required for the behavioural benefits of fluoxetine treatment. As to whether vesicular zinc is required for the neurogenic effects of fluoxetine, our results were inconclusive, warranting further investigation into the role of vesicular zinc in adult hippocampal neurogenesis.