bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brittleness in model selection analysis of single neuron firing rates
Authors: Chandrasekaran Chandramouli , Soldado-Magraner Joana , Peixoto Diogo , Newsome William T. , Shenoy Krishna V. , Sahani Maneesh 
Published: September 2018

AbstractModels of complex heterogeneous systems like the brain are inescapably incomplete, and thus always falsified with enough data. As neural data grow in volume and complexity, absolute measures of adequacy are being replaced by model selection methods that rank the relative accuracy of competing theories. Selection still depends on incomplete mathematical instantiations, but the implicit expectation is that ranking is robust to their details. Here we highlight a contrary finding of “brittleness,” where data matching one theory conceptually are ranked closer to an instance of another. In particular, selection between recent models of decision making is conceptually misleading when data are simulated with minor distributional mismatch, with mixed secondary signals, or with non-stationary parameters; and decision-related responses in macaque cortex show features suggesting that these effects may impact empirical results. We conclude with recommendations to mitigate such brittleness when using model selection to study neural signals.
System-level analysis of metabolic trade-offs during anaerobic photoheterotrophic growth inRhodopseudomonas palustris
Authors: Navid Ali , Jiao Yongqin , Wong Sergio Ernesto , Pett-Ridge Jennifer 
Published: September 2018

AbstractBackgroundLiving organisms need to allocate their limited resources in a manner that optimizes their overall fitness by simultaneously achieving several different biological objectives. Examination of these biological trade-offs can provide invaluable information regarding the biophysical and biochemical bases behind observed cellular phenotypes. A quantitative knowledge of a cell system’s critical objectives is also needed for engineering of cellular metabolism, where there is interest in mitigating the fitness costs that may result from human manipulation.ResultsTo study metabolism in photoheterotrophs, we developed and validated a genome-scale model of metabolism inRhodopseudomonas palustris, a metabolically versatile gram-negative purple non-sulfur bacterium capable of growing phototrophically on various carbons sources, including inorganic carbon and aromatic compounds. To quantitatively assess trade-offs among a set of important biological objectives during different metabolic growth modes, we used our new model to conduct an 8-dimensional multi-objective flux analysis of metabolism inR. palustris. Our results revealed that phototrophic metabolism inR. palustrisis a light-limited growth mode under anaerobic conditions, regardless of the available carbon source. Under photoheterotrophic conditions,R. Palustrisprioritizes the optimization of carbon efficiency, followed by ATP production and biomass production rate, in a Pareto-optimal manner. To achieve maximum carbon fixation, cells appear to divert limited energy resources away from growth and toward CO2fixation, even in presence of excess reduced carbon. We also found that to achieve the theoretical maximum rate of biomass production, anaerobic metabolism requires import of additional compounds (such as protons) to serve as electron acceptors. Finally, we found that production of hydrogen gas, of potential interest as a candidate biofuel, lowers the cellular growth rates under all circumstances.ConclusionsPhotoheterotrophic metabolism ofR. palustrisis primarily regulated by the amount of light it can absorb and not the availability of carbon. However, despite carbon’s secondary role as a regulating factor,R. palustris’metabolism strives for maximum carbon efficiency, even when this increased efficiency leads to slightly lower growth rates.
14-helical β-peptides Elicit Toxicity againstC. albicansby Forming Pores in the Cell Membrane and Subsequently Disrupting Intracellular Organelles
Authors: Lee Myung-Ryul , Raman Namrata , Ortiz-Bermudez Patricia , Lynn David M. , Palecek Sean P. 
Published: September 2018

SummarySynthetic peptidomimetics of antimicrobial peptides are promising as antimicrobial drug candidates because they promote membrane disruption and exhibit greater structural and proteolytic stability. We previously reported selective antifungal 14-helical β-peptides, but the mechanism of antifungal toxicity of β-peptides remains unknown. To provide insight into the mechanism, we studied antifungal β-peptide binding to artificial membranes and livingCandida albicanscells. We investigated the ability of β-peptides to interact with and permeate small unilamellar vesicle models of fungal and bacterial membranes. The partition coefficient supported a pore-mediated mechanism characterized by the existence of a critical β-peptide concentration separating low and high partition coefficient regimes. Live cell intracellular tracking of β-peptides showed that β-peptides translocated into the cytoplasm, and then disrupted the nucleus and vacuole sequentially, leading to cell death. This understanding of the mechanisms of antifungal activity will facilitate design and development of peptidomimetic AMPs, including 14-helical β-peptides, for antifungal applications.Graphical Abstract
Ethanol decreases Pseudomonas aeruginosa flagellar motility through a cyclic-di-GMP- and stator-dependent pathway
Authors: Lewis Kimberley A. , Baker Amy E. , Chen Annie I. , Harty Colleen E. , Kuchma Sherry L. , O’Toole George A. , Hogan Deborah A. 
Published: September 2018

AbstractPseudomonas aeruginosa frequently encounters microbes that produce bioactive metabolites including ethanol. At concentrations that do not affect growth, we found that ethanol reduces P. aeruginosa motility by 30% in a swim agar assay and this decrease is accompanied by a 2.5-fold increase in levels of cyclic diguanylate (c-di-GMP), a second messenger that represses motility, in planktonic cells. A screen of mutants lacking genes involved in c-di-GMP metabolism identified SadC and GcbA as diguanylate cyclases involved in swim zone reduction by ethanol and ethanol-induced c-di-GMP production. The reduction of swimming in response to ethanol also required the stator set, MotAB, two PilZ-domain proteins (FlgZ and PilZ), PilY1-a proposed surface-sensing protein, and PilMNOP, which comprises the pilus alignment complex and these proteins have been previously implicated in the control of motility on agar surfaces. Microscopic analysis of the fraction of quiescent cells in swim medium showed that ethanol decreased the portion of motile cells in the wild type, but had opposite effects in the ∆pilY1, ∆pilMNOP, ∆motAB, and ∆pilZ∆flgZ mutants. Together, these data indicate ethanol induces a regulated change in motility in planktonic cells at concentrations similar to those produced by other microbes. We propose that this ethanol-responsiveness may contribute to the co-localization of P. aeruginosa with ethanol-producing microbes.
Induction of Sertoli cells from human fibroblasts by NR5A1 and GATA4
Authors: Liang Jianlin , Wang Nan , He Jing , Du Jian , Guo Yahui , Li Lin , Kee Kehkooi 
Published: September 2018

AbstractSertoli cells are essential nurse cells in the testis that regulate the process of spermatogenesis and establish the immune-privileged environment of the blood-testis-barrier (BTB). The induction of human Sertoli cells from fibroblasts could provide cellular sources for fertility and transplantation treatments. Here, we report thein vitroreprogramming of human fibroblasts to Sertoli cells and characterize these human induced Sertoli cells (hiSCs). Initially, five transcriptional factors (NR5A1, GATA4, WT1, SOX9 and DMRT1) and a gene reporter carrying the AMH promoter were utilized to obtain the hiSCs. We further reduce the number of reprogramming factors to two, i.e., NR5A1 and GATA4, and show that these hiSCs have transcriptome profiles that are similar to those of primary human Sertoli cells. Consistent with the known cellular properties of Sertoli cells, hiSCs attract endothelial cells and exhibit high number of lipid droplets in the cytoplasm. More importantly, hiSCs can sustain the viability of spermatogonia cells harvested from mouse seminiferous tubules. In addition, hiSCs suppress the production of IL-2 and proliferation of human T lymphocytes. When hiSCs were cotransplanted with human embryonic kidney cells, these xenotransplanted human cells survived longer in mice with normal immune systems. hiSCs also allow us to determine a gene associated with Sertoli-only syndrome (SCO),CX43, is indeed important in regulating the maturation of Sertoli cells.
Investigation of putative regulatory acetylation sites in Fas2p ofSaccharomyces cerevisiae
Authors: Bergman Alexandra , Wenning Leonie , Siewers Verena , Nielsen Jens 
Published: September 2018

AbstractYeast metabolism is highly regulated, in part via coordinated reprogramming of metabolism on a transcriptional level, for example in response to environmental changes. Furthermore, regulation occurs on the protein level via posttranslational modifications directly affecting enzymatic activity – a mode of regulation that has the benefit of being very fast in response to environmental changes. One group of posttranslational modification that has been suggested to have a high impact on regulation of metabolism are acetylations. Around 4000 distinct protein acetylation sites have been found inSaccharomyces cerevisiae, many of which are located in central metabolic enzymes. However, reports on the verification of regulatory roles of specific acetylation sites on these metabolic enzymes have yet to emerge. This study investigates putative regulatory acetylation sites on Fas2p, which in concert with Fas1p is responsible for cytosolic fatty acid (FA) biosynthesis inS. cerevisiae. Fas2p stands out as one of the most highly acetylated proteins in yeast and is located at a branchpoint of acetyl-CoA metabolism. The amino acids (AAs) glutamine (Q) and arginine (R) were introduced to mimic a constitutively acetylated or non-acetylatable state at three separate lysine sites (K) (K83, K173 and K1551) confirmed to be acetylated in two independent studies, either separately or simultaneously. The results suggest that the residue replacement system in the specific case interferes with the enzymatic function of the fatty acid synthase (FAS), as QQQ and RRR triple mutants both reduce the amount of secreted free fatty acids (FFAs) in afaa1Δfaa4Δ yeast deletion mutant. The K173Q substitution significantly decreased C16 FA species at the expense of C18 FAs, while no such change could be observed for the corresponding K173R modification.
A molecular mechanism for salt stress-induced microtubule array formation in Arabidopsis
Authors: Kesten Christopher , Wallmann Arndt , Schneider René , McFarlane Heather E. , Diehl Anne , Abbas Khan Ghazanfar , van Rossum Barth-Jan , Lampugnani Edwin , Cremer Nils , Schmieder Peter , Ford Kristina L. , Seiter Florian , Heazlewood Joshua L. , Sanchez-Rodriguez Clara , Oschkinat Hartmut , Persson Staffan 
Published: September 2018

AbstractMicrotubules are filamentous structures necessary for cell division, motility and morphology, with dynamics critically regulated by microtubule-associated proteins (MAPs). We outline the molecular mechanism by which the MAP, COMPANION OF CELLULOSE SYNTHASE1 (CC1), controls microtubule bundling and dynamics to sustain plant growth under salt stress. CC1 contains an intrinsically disordered N-terminus that links microtubules at evenly distributed distances through four conserved hydrophobic regions. NMR analyses revealed that two neighboring residues in the first hydrophobic binding motif are crucial for the microtubule interaction, which we confirmed through live cell analyses. The microtubule-binding mechanism of CC1 is remarkably similar to that of the prominent neuropathology-related protein Tau, indicating evolutionary convergence of MAP functions across animal and plant cells.
Par protein localization during the early development ofMnemiopsis leidyisuggests different modes of epithelial organization in Metazoa
Authors: Salinas-Saavedra Miguel , Martindale Mark Q 
Published: September 2018

ABSTRACTIn bilaterians and cnidarians, embryonic and epithelial cell-polarity are regulated by the interactions between Par proteins, Wnt/PCP signaling pathway, and cell-cell adhesion. Par proteins are highly conserved across Metazoa, including ctenophores. But strikingly, ctenophore genomes lack components of the Wnt/PCP pathway and cell-cell adhesion complexes; raising the question if ctenophore cells are polarized by mechanisms involving Par proteins. Here, by using immunohistochemistry and live-cell imaging overexpression of specific mRNAs, we describe for the first time the subcellular localization of selected Par proteins in blastomeres and epithelial cells during the embryogenesis of the ctenophoreMnemiopsis leidyi. We show that these proteins distribute differently compared to what has been described for other animals, even though they segregate in a host-specific fashion when expressed in cnidarian embryos. This differential localization might be related to the emergence of different junctional complexes during metazoan evolution. Data obtained here challenge the ancestry of the apicobasal cell polarity and raise questions about the homology of epithelial tissue across the Metazoa.
Everyday taxi drivers: Do better navigators have larger hippocampi?
Authors: Weisberg Steven M. , Newcombe Nora S. , Chatterjee Anjan 
Published: September 2018

AbstractWork with non-human animals and human navigation experts (London taxi drivers) suggests that the size of the hippocampus, particularly the right posterior hippocampus in humans, relates to navigation expertise. Similar observations, sometimes implicating other sections of the hippocampus, have been made for aging populations and for people with neurodegenerative diseases that affect the hippocampus. These data support the hypothesis that hippocampal volume relates to navigation ability. However, the support for this hypothesis is mixed in healthy, young adults, who range widely in their navigation ability. Here, we administered a naturalistic navigation task that measures cognitive map accuracy to a sample of 90 healthy, young adults who also had MRI scans. Using a sequential analysis design with a registered analysis plan, we did not find that navigation ability related to hippocampal volume (total, right only, right posterior only). We conclude that navigation ability in a typical population does not correlate with variations in hippocampal size, and consider possible explanations for this null result.
Linking YAP to Müller glia quiescence exit in the degenerative retina
Authors: Hamon Annaïg , Ail Divya , García-García Diana , Bitard Juliette , Dalkara Deniz , Locker Morgane , Roger Jérôme , Perron Muriel 
Published: September 2018

AbstractContrasting with fish or amphibian, retinal regeneration from Müller glial cells is largely limited in mammals. In our quest towards the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP, which we previously found to be upregulated in Müller cells following retinal injury. We report that conditionalYapdeletion in Müller cells prevents the upregulation of cell cycle genes that normally accompanies reactive gliosis upon photoreceptor cell death. This occurs as a consequence of defective EGFR signaling. Consistent with a function of YAP in triggering Müller glia cell cycle re-entry, we further show that inXenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. Finally, and noteworthy, we reveal that YAP overactivation in mouse Müller cells is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Müller cell response to injury and highlight a novel YAP-EGFR axis by which Müller cells exit their quiescence state, a critical step towards regeneration.
The inherent multidimensionality of temporal variability: How common and rare species shape stability patterns
Authors: Arnoldi Jean-François , Loreau Michel , Haegeman Bart 
Published: September 2018

AbstractEmpirical knowledge of ecosystem stability and diversity-stability relationships is mostly based on the analysis of temporal variability of population and ecosystem properties. Variability, however, often depends on external factors that act as disturbances, making it difficult to compare its value across systems and relate it to other stability concepts. Here we show how variability, when viewed as a response to stochastic perturbations, can reveal inherent stability properties of ecological communities, with clear connections with other stability notions. This requires abandoning one-dimensional representations, in which a single variability measurement is taken as a proxy for how stable a system is, and instead consider the whole set of variability values associated to a given community, reflecting the whole set of perturbations that can generate variability. Against the vertiginous dimensionality of the perturbation set, we show that a generic variability-abundance pattern emerges from community assembly, which relates variability to the abundance of perturbed species. As a consequence, the response to stochastic immigration is governed by rare species while common species drive the response to environmental perturbations. In particular, the contrasting contributions of different species abundance classes can lead to opposite diversity-stability patterns, which can be understood from basic statistics of the abundance distribution. Our work shows that a multidimensional perspective on variability allows one to better appreciate the dynamical richness of ecological systems and the underlying meaning of their stability patterns.
StPOPA, encoding an anionic peroxidase in Solanum tuberosum, enhances resistance against Phytophthora infestans
Authors: Yang Yu , Jiang Rui , Wang Hongyang , Tian Zhendong , Xie Conghua 
Published: September 2018

AbstractPotato late blight, caused by Phytophthora infestans, is one of the major threats affecting the quality and output of potato all over the world. Reactive oxygen species (ROS) acted as a signal molecule to transmit signals in plants at the early stage of disease infection, and it could induce disease resistance of the plant, including potato late blight. Anionic peroxidases in many plants were reported to be involved in defense to disease. However, limited information about anionic peroxidase genes is available for the potato. Here, we reported that the expression of the StPOPA, a gene encoding a suberization-associated anionic peroxidase, was associated with resistance in potato against P. infestans. The StPOPA gene was induced by P. infestans infection, mechanical damage, jasmonic acid and ethylene treatment. Overexpression of the StPOPA gene in potato enhanced the resistance against P. infestans via promoting the accumulation of callose in the cell wall and ROS in the cytoplasm, which restricted the infection and spreading of the disease possibly by purposeful programmed cell death. Taken together, our results suggested that the StPOPA gene contributed to potato immunity against P. infestans and this gene could be used for the genetic improvement of resistance against potato late blight.
Interaction of taste and place coding in the hippocampus
Authors: Herzog Linnea E. , Pascual Leila May , Scott Seneca J. , Mathieson Elon R. , Katz Donald B. , Jadhav Shantanu P. 
Published: September 2018

AbstractAn animal’s survival depends on finding food, and the memory of food and contexts are often linked. Given that the hippocampus is required for spatial and contextual memory, it is reasonable to expect related coding of space and food stimuli in hippocampal neurons. However, relatively little is known about how the hippocampus responds to tastes, the most central sensory property of food. In this study, we examined the taste-evoked responses and spatial firing properties of single units in the dorsal CA1 hippocampal region as male rats received a battery of taste stimuli differing in both chemical composition and palatability within a specific spatial context. We identified a subset of hippocampal neurons that responded to tastes, some of which were place cells. These taste and place responses had a distinct interaction: taste-responsive cells tended to have less spatially specific firing fields, and place cells only responded to tastes delivered inside their place field. Like neurons in the amygdala and lateral hypothalamus, hippocampal neurons discriminated between tastes predominantly on the basis of palatability, with taste-selectivity emerging concurrently with palatability-relatedness; these responses did not reflect movement or arousal. However, hippocampal taste responses emerged several hundred msec later than responses in other parts of the taste system, suggesting that the hippocampus does not influence real-time taste decisions, instead associating the hedonic value of tastes with a particular context. This incorporation of taste responses into existing hippocampal maps could be one way that animals use past experience to locate food sources.Significance statementFinding food is essential for animals’ survival, and taste and context memory are often linked. While hippocampal responses to space and contexts have been well characterized, little is known about how the hippocampus responds to tastes. Here, we identified a subset of hippocampal neurons that discriminated between tastes based on palatability. Cells with stronger taste responses typically had weaker spatial responses, and taste responses were confined to place cells’ firing fields. Hippocampal taste responses emerged later than in other parts of the taste system, suggesting that the hippocampus does not influence taste decisions, but rather, associates the hedonic value of tastes consumed within a particular context. This could be one way that animals use past experience to locate food sources.
Internal bias controls dopamine perceptual decision-related responses
Authors: Sarno Stefania , Beirán Manuel , Vergara José , Rossi-Pool Román , Romo Ranulfo , Parga Néstor 
Published: September 2018

AbstractDopamine neurons produce reward-related signals that regulate learning and guide behavior. Prior expectations about forthcoming stimuli and internal biases can alter perception and choices and thus could influence dopamine signaling. We tested this hypothesis studying dopamine neurons recorded in monkeys trained to discriminate between two tactile frequencies separated by a delay period, a task affected by the contraction bias. The bias greatly controlled the animals’ choices and confidence on their decisions. During decision formation the phasic activity reflected bias-induced modulations and simultaneously coded reward prediction errors. In contrast, the activity during the delay period was not affected by the bias, was not tuned to the value of the stimuli but was temporally modulated, pointing to a role different from that of the phasic activity.
Pooled functional genomic screens for intracellular calcium effectors
Authors: Rao Anjali , Kralj Joel M. 
Published: October 2018

AbstractCytoplasmic calcium transients relay cellular signals on timescales from milliseconds to hours, and the dynamic nature of calcium signals has slowed functional genomic screening for cellular calcium effectors. Here, we present a new strategy to identify calcium handling genes via a pooled knockdown employing the calcium-sensitive photo-switchable fluorescent protein, CaMPARI. This assay, cal-Seq, enabled identification of regulators for both cellular desensitization and histamine induced calcium signaling including GPR99, a leukotriene binding receptor, with implications in asthma treatment.