bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure of human PACRG in complex with MEIG1
Authors: Khan Nimra , Pelletier Dylan , Veyron Simon , Croteau Nathalie , Ichikawa Muneyoshi , Black Corbin , Khalifa Ahmad Abdelzaher Zaki , Chaaban Sami , Kurinov Igor , Brouhard Gary , Bui Khanh Huy , Trempe Jean-François 
Published: September 2019

AbstractIn human, the Parkin Co-Regulated Gene (PACRG) shares a bidirectional promoter with Parkin, a gene involved in Parkinson’s disease, mitochondrial quality control and inflammation. The PACRG protein is essential to the formation of the inner junction between doublet microtubules of the axoneme, a structure found in flagella and cilia. PACRG interacts with tubulin as well as the meiosis expressed gene 1 (MEIG1) protein, which is essential for spermiogenesis in mice. However, the 3D structure of human PACRG is unknown. Here, we report the crystal structure of the C-terminal domain of human PACRG in complex with MEIG1 at 2.1 Å resolution. PACRG adopts an α-helical structure with a loop insertion that mediates a conserved network of interactions with MEIG1. Using the cryo-electron tomography structure of the axonemal doublet microtubule from the flagellated protozoan Chlamydomonas reinhardtii, we generate a model of a mammalian microtubule doublet inner junction, which reveals how PACRG interacts with tubulin subunits in both the A- and B-tubules. Furthermore, the model shows that MEIG1 interacts with β-tubulin on the outer surface of the B-tubule, facing towards the central pair of the axoneme. We also model the PACRG-like protein (PACRGL), a homolog of PACRG with potential roles in microtubule remodelling and axonemal inner junction formation. Finally, we explore the evolution of the PACRG and Parkin head-to-head gene structure and analyze the tissue distribution of their transcripts. Our work establishes a framework to assess the function of the PACRG family of proteins and its adaptor proteins in the function of motile and non-motile cilia.
How to define and optimize axial resolution in light-sheet microscopy: a simulation-based approach
Authors: Remacha Elena , Friedrich Lars , Vermot Julien , Fahrbach Florian O. 
Published: September 2019

Abstract“How thick is your light sheet?” is a question that has been asked frequently after talks showing impressive renderings of 3D data acquired by a light-sheet microscope. This question is motivated by the fact that most of the time the thickness of the light-sheet is uniquely associated to the axial resolution of the microscope. However, the link between light-sheet thickness and axial resolution has never been systematically assessed and it is still unclear how both are connected. The question is not trivial because commonly employed measures cannot readily be applied or do not lead to easily interpretable results for the many different types of light sheet. Here, by using simulation data we introduce a set of intuitive measures that helps to define the relationship between light sheet thickness and axial resolution. Unexpectedly, our analysis revealed a trade-off between better axial resolution and thinner light-sheet thickness. Our results are surprising because thicker light-sheets that provide lower image contrast have previously not been associated with better axial resolution. We conclude that classical Gaussian illumination beams should be used when image contrast is most important, and more advanced types of illumination represent a way to optimize axial resolution at the expense of image contrast.
High photon count rates improve the quality of super-resolution fluorescence fluctuation spectroscopy
Authors: Schneider Falk , Hernandez-Varas Pablo , Lagerholm B. Christoffer , Shrestha Dilip , Sezgin Erdinc , Roberti M. Julia , Ossato Giulia , Hecht Frank , Eggeling Christian , Urbančič Iztok 
Published: September 2019

AbstractProbing the diffusion of molecules has become a routine measurement across the life sciences, chemistry and physics. It provides valuable insights into reaction dynamics, oligomerisation, molecular (re-)organisation or cellular heterogeneities. Fluorescence correlation spectroscopy (FCS) is one of the widely applied techniques to determine diffusion dynamics in two and three dimensions. This technique relies on the temporal autocorrelation of intensity fluctuations but recording these fluctuations has thus far been limited by the detection electronics, which could not efficiently and accurately time-tag photons at high count rates. This has until now restricted the range of measurable dye concentrations, as well as the data quality of the FCS recordings, especially in combination with super-resolution stimulated emission depletion (STED) nanoscopy.Here, we investigate the applicability and reliability of (STED-)FCS at high photon count rates (average intensities of up to 40 MHz) using novel detection equipment, namely hybrid detectors and real-time gigahertz sampling of the photon streams implemented on a commercial microscope. By measuring the diffusion of fluorophores in solution and cytoplasm of live cells, as well as in model and cellular membranes, we show that accurate diffusion and concentration measurements are possible in these previously inaccessible high photon count regimes. Specifically, it offers much greater flexibility of experiments with biological samples with highly variable intensity, e.g. due to a wide range of expression levels of fluorescent proteins. In this context, we highlight the independence of diffusion properties of cytosolic GFP in a concentration range of approx. 0.01–1 μM. We further show that higher photon count rates also allow for much shorter acquisition times, and improved data quality. Finally, this approach also pronouncedly increases the robustness of challenging live cell STED-FCS measurements of nanoscale diffusion dynamics, which we testify by confirming a free diffusion pattern for a fluorescent lipid analogue on the apical membrane of adherent cells.
OPETH: Open Source Solution for Real-time Peri-event Time Histogram Based on Open Ephys
Authors: Széll András , Martínez-Bellver Sergio , Hegedüs Panna , Hangya Balázs 
Published: September 2019

AbstractSingle cell electrophysiology remains one of the most widely used approaches of systems neuroscience. Real-time feedback during electrophysiology experiments is important to guide experimental decisions that eventually determine the quality of recording, duration of the project and value of the collected data. We present an open-source tool that enables flexible online visualization of action potential alignment to external events, called the peri-event or peristimulus time histogram (OPETH). Based on the Open Ephys open source data acquisition system, we developed a Python interface for real-time plotting of neuronal spike times and evoked waveforms with respect to external events represented by digital logic signals. These digital inputs may signal photostimulation time stamps for in vivo optogenetic identification of cell types or the times of behaviorally relevant events during in vivo behavioral neurophysiology experiments. Therefore, OPETH allows real-time identification of genetically defined neuron types or behaviorally responsive populations. By allowing ‘hunting’ for neurons of interest, OPETH may significantly increase the efficiency of experiments that combine in vivo electrophysiology with behavior or optogenetic tagging of neurons.
Distances walked by beach users and protecting shorebird habitat zones from disturbance
Authors: Totterman Stephen 
Published: September 2019

ABSTRACTHuman population growth along Australia’s coast is increasing development and recreation pressures on beaches and shorebirds. This study observed human recreation on 18 beaches on the far north coast of New South Wales in February and March 2019. The far north coast supports the largest numbers of beach-resident Australian Pied Oystercatchers Haematopus longirostris in the State. The most frequent activities observed were walking (29%), dog walking (21%) and swimming (16%). Walkers covered greater distances compared to other beach users. For beach walkers and dog walkers combined, the mean along shore distance walked from an access point was 809 m and the 95th percentile was 1990 m. Noting that human recreation disturbance is a major conservation threat to beach nesting birds and that pro-environmental behaviour is uncommon among beach users, large separation distances between beach access points and shorebird habitat zones are recommended to reduce human intrusions into those zones. This spatial zoning and passive human exclusion strategy can be applied to long and less-developed beaches.
The Manganese Salt (MnJ) Functions as A Potent Universal Adjuvant
Authors: Zhang Rui , Wang Chenguang , Guan Yukun , Wei Xiaoming , Sha Mengyin , Jing Miao , Lv Mengze , Xu Jing , Wan Yi , Jiang Zhengfan 
Published: September 2019

AbstractAluminum adjuvants have been used for a century in various vaccines due to its ability to potentiate humoral immunity and safety records since 1920s. Manganese is an essential micronutrient required for diverse biological activities in cells. We previously found that Mn2+ is a strong type I-interferon stimulator activating the cGAS-STING pathway. Herein we report that a colloidal manganese salt (MnJ) is a potent adjuvant to induce both humoral and cellular immune responses, particularly CTL activation. When administrated intranasally, MnJ was also a strong mucosal adjuvant, inducing high levels of IgA antibodies. MnJ strongly promoted dendritic cell maturation and antigen-specific T cell activation. Interestingly, IL-1/-18 induction and release by Mn2+-activated ASC-mediated inflammasomes were not observed. MnJ showed great adjuvant effects to all tested antigens including inactivated viruses, recombinant proteins and peptides by either intramuscular or intranasal immunization. These findings may have implications in developing potent but safe Mn2+-containing vaccines.
Benthic jellyfish dominate water mixing in mangrove ecosystems
Authors: Durieux David M. , Du Clos Kevin T. , Gemmell Brad J. 
Published: September 2019

AbstractWater mixing is a critical mechanism in marine habitats that governs many important processes, including nutrient transport. Physical mechanisms, such as winds or tides, are primarily responsible for mixing effects in shallow coastal systems, but the sheltered habitats adjacent to mangroves experience very low turbulence and vertical mixing. The significance of biogenic mixing in pelagic habitats has been investigated but remains unclear. In this study we show that the upside-down jellyfish Cassiopea sp. plays a significant role with respect to biogenic contributions to water column mixing within its shallow natural habitat (< 2 m deep). The mixing contribution was determined by means of high-resolution flow velocimetry methods in both the laboratory and in the natural environment. We demonstrate that Cassiopea sp. continuously pumps water from the benthos upward in a vertical jet with flow velocities on the scale of centimeters per second. The volumetric flow rate was calculated to be 212 l h−1 for average sized animals (8.6 cm bell diameter), which translates to turnover of the entire water column every 15 minutes for a median population density (29 animals m−2). In addition, we found Cassiopea sp. are capable of releasing porewater into the water column at an average rate of 2.64 ml h−1 per individual. The release of nutrient-rich benthic porewater combined with strong contributions to water column mixing, suggest a role for Cassiopea sp. as an ecosystem engineer in mangrove habitats.Significance StatementWater mixing is a critical process for aquatic life. Coastal mangrove habitats are vital nurseries for commercially and ecologically important species, but these sheltered habitats experience little water mixing. The upside-down jellyfish, Cassiopea sp., occurs in circumtropical mangrove habitats at high densities. They are epibenthic and pulse nearly continuously, producing a vertical current that transports hundreds of liters of seawater per hour. This results in turnover of the entire water column every 15 minutes for an average population. Additionally, Cassiopea sp. can greatly expedite the transport of nutrient-rich water from sediments into the water column. Thus, Cassiopea sp. represents a previously unrecognized ecosystem engineer that can affect primary productivity, nutrient distribution, and alter new habitats as their range is expanding.
Molecular Atlas of the Adult Mouse Brain
Authors: Ortiz Cantin , Navarro Jose Fernandez , Jurek Aleksandra , Märtin Antje , Lundeberg Joakim , Meletis Konstantinos 
Published: September 2019

AbstractBrain maps are essential for integrating information and interpreting the structure-function relationship of circuits and behavior. We aimed to generate a systematic classification of the adult mouse brain organization based on unbiased extraction of spatially-defining features. Applying whole-brain spatial transcriptomics, we captured the gene expression signatures to define the spatial organization of molecularly discrete subregions. We found that the molecular code contained sufficiently detailed information to directly deduce the complex spatial organization of the brain. This unsupervised molecular classification revealed new area- and layer-specific subregions, for example in isocortex and hippocampus, and a new division of striatum. The whole-brain molecular atlas further supports the identification of the spatial origin of single neurons using their gene expression profile, and forms the foundation to define a minimal gene set - a brain palette – that is sufficient to spatially annotate the adult brain. In summary, we have established a new molecular atlas to formally define the identity of brain regions, and a molecular code for mapping and targeting of discrete neuroanatomical domains.
Regulation of BMP Signaling by O-GlcNAcylation
Authors: Moulton Matthew , Humphreys Greg , Kim Alexander , Letsou Anthea 
Published: September 2019

SummaryPrecise regulation of signal transduction is critical throughout organismal life, both for embryonic development and for adult homeostasis. To ensure proper spatio-temporal signal transduction, Bone Morphogenetic Protein (BMP) signaling pathways, like all other signaling pathways, are regulated by both agonists and antagonists. Here, we report identification of a previously unrecognized method of signal antagonism for Dpp (Decapentaplegic), aDrosophilaBMP family member. We demonstrate that the BMP type I receptor Saxophone (Sax) functions as a Dpp receptor in theDrosophilaembryonic epidermis, but that its activity is normally inhibited by the O-linked glycosyltransferase Super sex combs (Sxc). In wild-type embryos, inhibition of Saxophone (Sax) activity in the epidermis marks the BMP type I receptor Thickveins (Tkv) as the sole conduit for Dpp. In contrast, insxcmutants, the Dpp signal is transduced by both Tkv and Sax, and elevated Dpp signaling induces errors in embryonic development that lead to embryonic death. We also demonstrate that Sax is the O-glycosylated target of Sxc and that O-glycosylation of Sax can be modulated by dietary sugar. Together, these findings link fertility to nutritive environment and point to Sax (activin receptor-like kinase 2 [ACVR1 or ALK2]) signaling as the nutrient-sensitive branch of BMP signaling.Graphical Abstract
A Missense Point Mutation in Nerve Growth Factor (NGFR100W) Results in Selective Peripheral Sensory Neuropathy
Authors: Yang Wanlin , Sung Kijung , Xu Wei , Rodriguez Maria J , Wu Andrew C. , Santos Sarai A. , Fang Savannah , Uber Rebecca K. , Dong Stephanie X. , Guillory Brandon C. , Orain Xavier , Raus Jordan , Jolivalt Corrine , Calcutt Nigel , Rissman Robert A. , Ding Jianqing , Wu Chengbiao 
Published: September 2019

ABSTRACTA missense point mutation in nerve growth factor (NGFR100W) is associated with hereditary sensory autonomic neuropathy V (HSAN V), originally discovered in a Swedish family. These patients develop severe loss of perception to deep pain but with apparently normal cognitive functions. To better understand the disease mechanism, we have generated the first NGFR100Wknockin mouse model of HSAN V. Mice homozygous for the NGFR100Wmutation (NGFfln/fln) showed significant structural deficits in intra-epidermal nerve fibers (IENFs) at birth. These mice had a total loss of pain perception at ∼2 months of age and they often failed to survive to full adulthood. Heterozygous mice (NGF+/fln) developed a progressive degeneration of small sensory fibers both behaviorally and functionally: they showed a progressive loss of IENFs starting at the age of 9 months accompanied with progressive loss of perception to painful stimuli such as noxious temperature. Quantitative analysis of lumbar 4/5 dorsal root ganglia (DRG) revealed a significant reduction in small size neurons positive for calcitonin gene-related peptide, while analysis of sciatic nerve fibers revealed the mutant NGF+/flnmice had no reduction in myelinated nerve fibers. Significantly, the amount of NGF secreted from fibroblasts were reduced in heterozygous and homozygous mice compared to their wild-type littermates. Interestingly, NGF+/flnshowed no apparent structural alteration in the brain: neither the anterior cingulate cortex nor the medial septum including NGF-dependent basal forebrain cholinergic neurons. Accordingly, these animals did not develop appreciable deficits in tests for central nervous system function. Our study provides novel insights into the selective impact of NGFR100Wmutation on the development and function of the peripheral sensory system.
The role of 3’UTR-protein complexes in the regulation of protein multifunctionality and subcellular localization
Authors: Ribeiro Diogo M. , Prod’homme Alexis , Teixeira Adrien , Zanzoni Andreas , Brun Christine 
Published: September 2019

AbstractMultifunctional proteins often perform their different functions when localized in different subcellular compartments. However, the mechanisms leading to their localization are largely unknown. Recently, 3’UTRs were found to regulate the cellular localization of newly synthesized proteins through the co-translational formation of 3’UTR-protein complexes. Here, we investigate the formation of 3’UTR-protein complexes involving multifunctional proteins by exploiting large-scale protein-protein and protein-RNA interaction networks. Focusing on 238 human ‘extreme multifunctional’ (EMF) proteins, we predicted 1411 3’UTR-protein complexes involving 128 EMF proteins and evaluated their role in regulating protein cellular localization and multifunctionality. Notably, we find that EMF proteins lacking localization addressing signals, yet present at both the nucleus and cell surface, often form 3’UTR-protein complexes. In addition, they provide EMF proteins with the diversity of interaction partners necessary to their multifunctionality. Archetypal moonlighting proteins are also predicted to form 3’UTR-protein complexes thereby reinforcing our findings. Finally, our results indicate that the formation of 3’UTR-protein complex may be a common phenomenon in human cells, affecting up to 20% of the proteins in the human interactome.
FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences
Authors: Goering Raeann , Hudish Laura I. , Guzman Bryan B. , Raj Nisha , Bassell Gary J. , Russ Holger A. , Dominguez Daniel , Taliaferro J. Matthew 
Published: September 2019

ABSTRACTThe sorting of RNA molecules to distinct subcellular locations facilitates the activity of spatially restricted processes through local protein synthesis. This process affects thousands of transcripts yet precisely how these RNAs are trafficked to their destinations remains generally unclear. Here we have analyzed subcellular transcriptomes of FMRP-null mouse neuronal cells to identify transcripts that depend on FMRP for efficient transport to neurites. We found that these FMRP RNA localization targets contain a large enrichment of G-quadruplex sequences, particularly in their 3′ UTRs, suggesting that FMRP recognizes these sequences to promote the localization of transcripts that contain them. Fractionation of neurons derived from human Fragile X Syndrome patients revealed a high degree of conservation in the identity of FMRP localization targets between human and mouse as well as an enrichment of G-quadruplex sequences in human FMRP RNA localization targets. Using high-throughput RNA/protein interaction assays and single-molecule RNA FISH, we identified the RGG domain of FMRP as important for both interaction with G-quadruplex RNA sequences and the neuronal transport of G-quadruplex-containing transcripts. Finally, we used ribosome footprinting to identify translational regulatory targets of FMRP. The translational regulatory targets were not enriched for G-quadruplex sequences and were largely distinct from the RNA localization targets of FMRP, indicating that the two functions can be biochemically separated and are mediated through different target recognition mechanisms. These results establish a molecular mechanism underlying FMRP-mediated neuronal RNA localization and provide a framework for the elucidation of similar mechanisms governed by other RNA-binding proteins.
Information use in foraging flocks of songbirds - no evidence for social transmission of patch quality
Authors: Hillemann F. , Cole E. F. , Sheldon B. C. , Farine D. R. 
Published: September 2019

ABSTRACTAnimals use behavioural cues from others to make decisions in a variety of contexts. There is growing evidence, from a range of taxa, that information about the locations of food patches can spread through a population via social connections. However, it is not known whether information about the quality of potential food sources transmits similarly. We studied foraging behaviour in a population of wild songbirds with known social associations, and tested whether flock members use social information about the profitability of patches to inform their foraging decisions. We provided artificial patches (ephemeral bird feeders) that appeared identical but were either profitable (contained food) or unprofitable (contained no food). If information about patch profitability spreads via social associations, we predicted that empty feeders would only be sampled by individuals that are less connected to each other than expected by chance. In contrast, we found that individuals recorded at empty feeders were more closely associated with each other than predicted by a null model simulating random arrival of individuals, mirroring pattern of increased connectedness among individuals recorded at full feeders. We then simulated arrival under network-based diffusion of information, and demonstrate that the observed pattern at both full and empty feeders matches predictions derived from this post-hoc model. Our results suggest that foraging songbirds only use social cues about the location of potential food sources, but not their profitability. These findings agree with the hypothesis that individuals balance the relative economic costs of using different information, where the costs of personally sampling a patch upon arrival is low relative to the cost of searching for patches. This study extends previous work on information spread through avian social networks, by suggesting important links between how animals use information at different stages of the acquisition process and the emerging population-level patterns of patch use.