bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spike afterpotentials shape the in-vivo burst activity of principal cells in medial entorhinal cortex
Authors: Csordás Dóra É. , Fischer Caroline , Nagele Johannes , Stemmler Martin , Herz Andreas V.M. 
Published: November 2019

AbstractPrincipal neurons in rodent medial entorhinal cortex (MEC) generate high-frequency bursts during natural behavior. While in vitro studies point to potential mechanisms that could support such burst sequences, it remains unclear whether these mechanisms are effective under in-vivo conditions. In this study, we focused on the membrane-potential dynamics immediately following action potentials, as measured in whole-cell recordings from male mice running in virtual corridors (Domnisoru et al., 2013). These afterpotentials consisted either of a hyperpolarization, an extended ramp-like shoulder, or a depolarization reminiscent of depolarizing afterpotentials (DAPs) recorded in vitro in MEC stellate and pyramidal neurons. Next, we correlated the afterpotentials with the cells’ propensity to fire bursts. All DAP cells with known location resided in Layer II, generated bursts, and their inter-spike intervals (ISIs) were typically between five and fifteen milliseconds. The ISI distributions of Layer-II cells without DAPs peaked sharply at around four milliseconds and varied only minimally across that group. This dichotomy in burst behavior is explained by cell-group-specific DAP dynamics. The same two groups of bursting neurons also emerged when we clustered extracellular spike-train autocorrelations measured in real two-dimensional arenas (Latuske et al., 2015). No difference in the spatial coding properties of the grid cells across all three groups was discernible. Layer III neurons were only sparsely bursting and had no DAPs. As various mechanisms for modulating the ion-channels underlying DAPs exist, our results suggest that the temporal features of MEC activity can be altered while maintaining the cells’ spatial tuning characteristics.Significance StatementDepolarizing afterpotentials (DAPs) are frequently observed in principal neurons from slice preparations of rodent medial entorhinal cortex (MEC), but their functional role in vivo is unknown. Analyzing whole-cell data from mice running on virtual tracks, we show that DAPs do occur during behavior. Cells with prominent DAPs are found in Layer II; their inter-spike intervals reflect DAP time-scales. In contrast, neither the rarely bursting cells in Layer III, nor the high-frequency bursters in Layer II, have a DAP. Extracellular recordings from mice exploring real two-dimensional arenas demonstrate that grid cells within these three groups have rather similar spatial coding properties. We conclude that DAPs shape the temporal but not the spatial response characteristics of principal neurons in MEC.Author contributionsAll authors designed research. DÉC, CF, and JN performed research and analyzed data (equal contribution). AVMH wrote and edited the paper with support from MS and the other authors.
Moving by thoughts alone? Amount of finger movement and pendulum length determine success in the Chevreul Pendulum Illusion
Authors: Cantergi Debora , Awasthi Bhuvanesh , Friedman Jason 
Published: November 2019

AbstractHand-held pendulums can seemingly oscillate on their own, without perceived conscious control. This illusion, named after Chevreul, is likely a result of ideomotor movements. While this phenomenon was originally assumed to have a supernatural basis, it has been accepted for over 150 years that the movements are self-generated. However, until now, recordings of the small movements that create these oscillations has not been performed. In this study, we examined the mechanism that produces these significant involuntary oscillations using a motion capture system. We determined that the Chevreul pendulum illusion is produced when the fingers holding the pendulum generate an oscillating frequency close to the resonant frequency of the pendulum. At an appropriate frequency, very small driving movements of the arm are sufficient to produce relatively large pendulum motion. Further, subjects that tended to move their fingers more were more successful in producing the illusion.
Allosteric Regulation of Vitamin K2 Biosynthesis in a Human Pathogen
Authors: Bashiri Ghader , Nigon Laura V. , Jirgis Ehab N. M. , Ho Ngoc Anh Thu , Stanborough Tamsyn , Dawes Stephanie S. , Baker Edward N. , Bulloch Esther M. M. , Johnston Jodie M. 
Published: November 2019

AbstractMenaquinone (Vitamin K2) plays a vital role in energy generation and environmental adaptation in many bacteria, includingMycobacterium tuberculosis(Mtb). Although menaquinone levels are known to be tightly linked to the redox/energy status of the cell, the regulatory mechanisms underpinning this phenomenon are unclear. The first committed step in menaquinone biosynthesis is catalyzed by MenD, a thiamine diphosphate-dependent enzyme comprising three domains. Domains I and III form the MenD active site, but no function has yet been ascribed to domain II. Here we show the last cytosolicmetabolite in the menaquinone biosynthesis pathway (1,4-dihydroxy-2-napthoic acid, DHNA) binds to domain II ofMtb-MenD and inhibits enzyme activity. We identified three arginine residues (Arg97, Arg277 and Arg303) that are important for both enzyme activity and the feedback inhibition by DHNA: Arg277 appears to be particularly important for signal propagation from the allosteric site to the active site. This is the first evidence of feedback regulation of the menaquinone biosynthesis pathway in bacteria, unravelling a protein level regulatory mechanism for control of menaquinone levels within the cell.
Nonlinear stimulus representations in neural circuits with approximate excitatory-inhibitory balance
Authors: Baker Cody , Zhu Vicky , Rosenbaum Robert 
Published: November 2019

AbstractBalanced excitation and inhibition is widely observed in cortical recordings. How does this balance shape neural computations and stimulus representations? This problem is often studied using computational models of neuronal networks in a dynamically balanced state. However, these balanced network models predict a linear relationship between stimuli and population responses, in contrast to the nonlinearity of cortical computations. We show that every balanced network architecture admits some stimuli that break the balanced state and these breaks in balance push the network into a “semi-balanced state” characterized by excess inhibition to some neurons, but an absence of excess excitation. The semi-balanced state is unavoidable in networks driven by multiple stimuli, consistent with experimental data, has a direct mathematical relationship to artificial neural networks, and permits nonlinear stimulus representations and nonlinear computations.
Bacterial glycogen provides short-term benefits in changing environments
Authors: Sekar Karthik , Linker Stephanie M. , Nguyen Jen , Grünhagen Alix , Stocker Roman , Sauer Uwe 
Published: November 2019

AbstractChanging nutritional conditions challenge microbes and shape their evolutionary optimization. Here we investigated the role of glycogen in dynamic physiological adaptation of Escherichia coli to fluctuating nutrients following carbon starvation using real-time metabolomics. We found significant metabolic activity remaining after the depletion of environmental glucose that was linked to a rapid utilization of intracellular glycogen. Glycogen was depleted by 80% within minutes of glucose starvation and similarly replenished within minutes of glucose availability. These fast timescales of glycogen utilization correspond to the short-term benefits that glycogen provided to cells undergoing various physiological transitions. Cells capable of utilizing glycogen exhibited shorter lag times than glycogen mutants when starved between different carbon sources. The ability to utilize glycogen was also important for the transition between planktonic and biofilm lifestyles and enabled increased glucose uptake during pulses of limited glucose availability. While wild-type and mutant strains exhibited comparable growth rates in steady environments, mutants deficient in glycogen utilization grew more poorly in environments that fluctuated on minute-scales between carbon availability and starvation. Altogether, these results highlight an underappreciated role of glycogen to rapidly provide carbon and energy in changing environments, thereby increasing survival and competition capabilities in fluctuating and nutrient poor conditions.
Early-life gut dysbiosis linked to mass mortality in ostriches
Authors: Videvall Elin , Song Se Jin , Bensch Hanna M. , Strandh Maria , Engelbrecht Anel , Serfontein Naomi , Hellgren Olof , Olivier Adriaan , Cloete Schalk , Knight Rob , Cornwallis Charlie K. 
Published: November 2019

AbstractDysbiosis in the vertebrate gut microbiome has been associated with several diseases. However, it is unclear whether particular gut regions or specific time periods during ontogeny are responsible for the development of dysbiosis, especially in non-model organisms. Here we examine the microbiome associated with dysbiosis in different parts of the gastrointestinal tract (ileum, caecum, colon) in a long-lived bird with high juvenile mortality, the ostrich. Individuals that died of gut disease (n=68) had substantially different microbial composition from age-matched controls (n=50) throughout the gut. Several taxa were associated with mortality (Enterobacteriaceae, Peptostreptococcaceae, Porphyromonadaceae,Clostridium) and some with survival (Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae,Turicibacter). Repeated faecal sampling showed that pathobionts were already present shortly after hatching and proliferated in individuals with low diversity, resulting in mortality weeks later. The factors influencing seeding of the gut microbiota may therefore be key to understanding dysbiosis and host development.
Protein structure featurization via standard image classification neural networks
Authors: Sikosek Tobias 
Published: November 2019

ABSTRACTMany applications in the biomedical domain involve the detailed molecular and functional characterization of macro-molecules such as proteins. Where possible, this involves the knowledge of detailed 3D coordinates of every atom within a protein. At the same time, machine learning has become the basis of much innovation within this domain in recent years. There are, however, a few challenges in applying machine learning to 3D protein structures, such as variability in size and high dimensionality of the data. It would therefore be beneficial to be able to map every protein structure to a smaller fixed-dimensional representation that is directly learned from the structure without manual curation. In addition, it would be valuable for biomedical researchers if such approaches would require little method development and instead draw from cutting-edge research such as image classification via deep neural networks. Here, such an approach is outlined that first re-formats protein structures as 2D color images and then applies off-the-shelf neural networks for image classification. It is shown that such neural networks can be trained to effectively encode the CATH protein classification database and that feature vectors extracted from such networks, once trained, can be transferred to a completely new task that is likely to benefit from molecular protein information, namely that of small molecule binding.
Effects of an IgE receptor polymorphism acting on immunity, susceptibility to infection and reproduction in a wild rodent
Authors: Wanelik Klara M , Begon Mike , Bradley Janette E , Friberg Ida M , Jackson Joseph A , Taylor Christopher H , Paterson Steve 
Published: November 2019

AbstractThe genotype of an individual is an important predictor of their immune function, and subsequently, their ability to control or avoid infection and ultimately contribute offspring to the next generation. However, the same genotype, subjected to different intrinsic and/or extrinsic environments can also result in different phenotypic outcomes, which can be missed in controlled laboratory studies. Natural wildlife populations, which capture both genotypic and environmental variability, provide an opportunity to more fully understand the phenotypic expression of genetic variation. We identified a synonymous polymorphism in the high-affinity Immunoglobulin E (IgE) receptor (GC and non-GC haplotypes) that has sex-dependent effects on immune gene expression, susceptibility to infection and reproductive success of individuals in a natural population of field voles (Microtus agrestis). We found that the effect of the GC haplotype on the expression of immune genes differed between sexes. While males with the GC haplotype had upregulated more pro-inflammatory genes, including the cytokineIl33, females had upregulated more anti-inflammatory genes, including the cytokine inhibitorSocs3. Furthermore we found an effect of the GC haplotype on the probability of infection with a common microparasite, Babesia microti, in females - with females carrying the GC haplotype being more likely to be infected. Finally, we found an effect of the GC haplotype on reproductive success in males - with males carrying the GC haplotype having a lower reproductive success. This is a rare example of a polymorphism whose consequences we are able to follow across immunity, infection and reproduction for both males and females in a natural population.
Tumor microtubes connect pancreatic cancer cells in an Arp2/3 complex-dependent manner
Authors: Latario Casey J. , Schoenfeld Lori W. , Howarth Charles L. , Pickrell Laura E. , Begum Fatema , Fischer Dawn A. , Grbovic-Huezo Olivera , Leach Steven D. , Sanchez Yolanda , Smith Kerrington D. , Higgs Henry N. 
Published: November 2019

AbstractActin-based tubular connections between cells have been observed in many cell types. Termed “tunneling nanotubes (TNTs)”, “membrane nanotubes”, “tumor microtubes (TMTs)”, or “cytonemes”, these protrusions interconnect cells in dynamic networks. Structural features in these protrusions vary between cellular systems, including tubule diameter and presence of microtubules. We find tubular protrusions, which we classify as TMTs, in a pancreatic cancer cell line, DHPC-018. TMTs are present in DHPC-018-derived tumors in mice, as well as in a mouse model of pancreatic cancer and a sub-set of primary human tumors. DHPC-018 TMTs have heterogeneous diameter (0.39 – 5.85 μm, median 1.92 μm) and contain actin filaments, microtubules, and cytokeratin 19-based intermediate filaments. The actin filaments are cortical within the protrusion, as opposed to TNTs, in which filaments run down the center of the tube. TMTs are dynamic in length, but are long-lived (median > 60 min). Inhibition of actin polymerization, but not microtubules, results in TMT loss. A second class of tubular protrusion, which we term cell-substrate protrusion (CSP), has similar width range and cytoskeletal features but make contact with the substratum as opposed to another cell. Similar to previous work on TNTs, we find two assembly mechanisms for TMTs, which we term “pull-away” and “search-and-capture”. Inhibition of the Arp2/3 complex, an actin assembly factor, inhibits TMT assembly by both mechanisms. This work demonstrates that the actin architecture of TMTs is fundamentally different from that of TNTs, as well as demonstrating the role of Arp2/3 complex on TMT assembly.
The nuclear transport receptor TNPO1 binds macrophage immunometabolism regulator MACIR via a PY-NLS motif
Authors: McGauran Gavin , Dorris Emma , Borza Razvan , Morgan Niamh , Shields Denis C. , Matallanas David , Wilson Anthony G. , O’Connell David J. 
Published: November 2019

AbstractExpression of the macrophage immunometabolism regulator gene (MACIR) is associated with severity of autoimmune disease pathology and the regulation of macrophage biology through unknown mechanisms. The 206 amino acid protein lacks homology to any characterized protein sequence and is a disordered protein according to structure prediction algorithms. Here we identify specific interactions of MACIR using a fragment complementation-based affinity pull down of cellular proteins prepared with a membrane solubilization buffer. Quantitative mass spectrometry showed enrichment of nuclear and mitochondrial proteins and of 63 significant interacting proteins, binding to the nuclear transport receptor TNPO1 and trafficking proteins UNC119 homolog A and B were validated by immunoprecipitation. Analysis of mutations in two candidate recognition motifs in the MACIR amino acid sequence confirmed TNPO1 binds via a PY-NLS motif (aa98-117). Characterizing nuclear MACIR activity in macrophage and fibroblasts is a priority with respect to developing strategies for treatment of autoimmune disease.
Genomic epidemiology of vancomycin resistantEnterococcus faecium(VREfm) in Latin America: Revisiting the global VRE population structure
Authors: Rios Rafael , Reyes Jinnethe , Carvajal Lina P. , Rincon Sandra , Panesso Diana , Planet Paul J. , Echeverri Aura M. , Dinh An , Kolokotronis Sergios-Orestis , Narechania Apurva , Tran Truc T. , Munita Jose M. , Murray Barbara E. , Arias Cesar A. , Diaz Lorena 
Published: November 2019

AbstractThe prevalence of vancomycin-resistantEnterococcus faeciumvaries across geographical regions yet little is known about its population structure in Latin America. Here, we provide a complete genomic characterization of 55 representative Latin American VREfmrecovered from 1998-2015 in 5 countries. We found that VREfmpopulation in the region is structured into two main clinical clades without geographical clustering. To place our regional findings in context, we reconstructed the global population structure of VREfmby including 285 genomes from 36 countries from 1946-2017. Our results differ from previous studies showing an early branching of animal related isolates and a further split of clinical isolates into two sub-clades, all within clade A. The overall phylogenomic structure was highly dependent on recombination (54% of the genome) and the split between clades A and B is estimated to have occurred more than 3585 years BP. Furthermore, while the branching of animal isolates and clinical clades was predicted to have occur ∼894 years BP, our molecular clock calculations suggest that the split within the clinical clade occurred around ∼371 years BP. By including isolates from Latin America, we present novel insights into the population structure of VREfmand revisit the evolution of this pathogen.
Towards a scaled-up T cell-mediated cytotoxicity assay in 3D cell culture using microscopy
Authors: Gottschalk Elinor , Czech Eric , Aksoy Bulent Arman , Aksoy Pinar , Hammerbacher Jeff 
Published: November 2019

AbstractThree-dimensional (3D) cell culture systems with tumor spheroids are being adopted for research on the antitumor activity of drug treatments and cytotoxic T cells. Analysis of the cytotoxic effect on 3D tumor cultures within a 3D scaffold, such as collagen, is challenging. Image-based approaches often use confocal microscopy, which greatly limits the sample size of tumor spheroids that can be assayed. We explored a system where tumor spheroids growing in a collagen gel within a microfluidics chip can be treated with drugs or co-cultured with T cells. We attempted to adapt the system to measure the death of cells in the tumor spheroids directly in the microfluidics chip via automated widefield fluorescence microscopy. We were able to successfully measure drug-induced cytotoxicity in tumor spheroids, but had difficulties extending the system to measure T cell-mediated tumor killing.Abstract Figure
Foraging fruit flies mix navigational and learning-based decision-making strategies
Authors: Seidenbecher Sophie E. , Sanders Joshua I. , von Philipsborn Anne C. , Kvitsiani Duda 
Published: November 2019

AbstractAnimals often navigate environments that are uncertain, volatile and complex, making it challenging to locate reliable food sources. Therefore, it is not surprising that many species evolved multiple, parallel and complementary foraging strategies to survive. Current research on animal behavior is largely driven by a reductionist approach and attempts to study one particular aspect of behavior in isolation. This is justified by the huge success of past and current research in understanding neural circuit mechanisms of behaviors. But focusing on only one aspect of behaviors obscures their inherent multidimensional nature. To fill this gap we aimed to identify and characterize distinct behavioral modules using a simple reward foraging assay. For this we developed a single-animal, trial-based probabilistic foraging task, where freely walking fruit flies experience optogenetic sugar-receptor neuron stimulation. By carefully analyzing the walking trajectories of flies, we were able to dissect the animals foraging decisions into multiple underlying systems. We show that flies perform local searches, cue-based navigation and learn task relevant contingencies. Using probabilistic reward delivery allowed us to bid several competing reinforcement learning (RL) models against each other. We discover that flies accumulate chosen option values, forget unchosen option values and seek novelty. We further show that distinct behavioral modules -learning and navigation-based systems-cooperate, suggesting that reinforcement learning in flies operates on dimensionality reduced representations. We therefore argue that animals will apply combinations of multiple behavioral strategies to generate foraging decisions.
Distinct representational structure and localization for visual encoding and recall during visual imagery
Authors: Bainbridge Wilma A. , Hall Elizabeth H. , Baker Chris I. 
Published: November 2019

AbstractDuring memory recall and visual imagery, reinstatement is thought to occur as an echoing of the neural patterns during encoding. However, the precise information in these recall traces is relatively unknown, with previous work primarily investigating either broad distinctions or specific images, rarely bridging these levels of information. Using ultra-high-field (7T) fMRI with an item-based visual recall task, we conducted an in-depth comparison of encoding and recall along a spectrum of granularity, from coarse (scenes, objects) to mid (e.g., natural, manmade scenes) to fine (e.g., living room, cupcake) levels. In the scanner, participants viewed a trial-unique item, and after a distractor task, visually imagined the initial item. During encoding, we observed decodable information at all levels of granularity in category-selective visual cortex. In contrast, information during recall was primarily at the coarse level with fine level information in some areas; there was no evidence of mid-level information. A closer look revealed segregation between voxels showing the strongest effects during encoding and those during recall, and peaks of encoding-recall similarity extended anterior to category-selective cortex. Collectively, these results suggest visual recall is not merely a reactivation of encoding patterns, displaying a different representational structure and localization from encoding, despite some overlap.