bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergence of socio-ecological dynamics in disparate ecological systems under strong coupling to human social systems
Authors: Sigdel Ram , Anand Madhur , Bauch Chris T. 
Published: April 2018

AbstractIt is widely recognized that coupled socio-ecological dynamics can be qualitatively different from the dynamics of social or ecological systems in isolation from one another. The influence of the type of ecological dynamics on the dynamics of the larger socio-ecological system is less well studied, however. Here, we carry out such a comparison using a mathematical model of a common pool resource problem. A population must make decisions about harvesting a renewable resource. Individuals may either be cooperators, who harvest at a sustainable level, or defectors, who over-harvest. Cooperators punish defectors through social ostracism. Individuals can switch strategies according the costs and benefits of harvesting and the strength of social ostracism. These mechanisms are represented by a differential equation for social dynamics which is coupled to three different types of resource dynamics: logistic growth, constant inflow, and threshold growth. We find that when human influence is sufficiently weak, the form of natural dynamics leaves a strong imprint on the socio-ecological dynamics, and human social dynamics are qualitatively very different from natural dynamics. However, stronger human influence introduces a broad intermediate parameter regime where dynamical patterns converge to a common type: the three types of ecological systems exhibit similar dynamics, but also, social and ecological dynamics strongly mirror one another. This is a consequence of stronger coupling and is reminiscent of synchrony from other fields, such as the classic problem of coupled oscillators in physics. Socio-ecological convergence has implications for how we understand and manage complex socio-ecological systems. In an era of growing human influence on ecological systems, further empirical and theoretical work is required to determine whether socio-ecological convergence is present in real systems.
Better than maximum likelihood estimation of model-based and model-free learning style
Authors: Yazdani Sadjad , Vahabie Abdol-Hossein , Araabi Babak Nadjar , Ahmadabadi Majid Nili 
Published: April 2018

AbstractMultiple decision making systems work together to shape the final choices in human behavior. Habitual and goal-directed systems are the two most important systems that are studied in the reinforcement learning (RL) literature by model-free and model-based learning methods. Human behavior resembles the weighted combination of these systems and such a combination is modeled by weighted summation of action’s value from the model based and model free systems. Extraction of this weighted parameter, which is important for many applications and computational modeling, has been mostly based on the maximum likelihood or maximum a posteriori methods. We show these methods bring many challenges and their respective extracted values are less reliable especially in the proximity of extremes values. We propose that using a free format learning method (k-nearest neighbor) which uses more information besides the fitted values e.g. global information like stay probability instead of trial by trial information can ameliorate the estimation error. The proposed method is examined by simulation and results show the advantage of the proposed method. In addition, investigation of the human behavior data from previous researchers proved the proposed method to result in more statistically robust results in predicting other behavioral indices such as the number of gaze directions toward each target. In brief, the proposed method increases the reliability of the estimated parameters and enhances the applicability of reinforcement learning paradigms in clinical trials.
Large and fast human pyramidal neurons associate with intelligence
Authors: Goriounova Natalia A. , Heyer Djai B. , Wilbers René , Verhoog Matthijs B. , Giugliano Michele , Verbist Christophe , Obermayer Joshua , Kerkhofs Amber , Smeding Harriët , Verberne Maaike , Idema Sander , Baayen Johannes C. , Pieneman Anton W. , de Kock Christiaan P.J. , Klein Martin , Mansvelder Huibert D. 
Published: April 2018

AbstractIt is generally assumed that human intelligence relies on efficient processing by neurons in our brain. Behavioral and brain-imaging studies robustly show that higher intelligence associates with faster reaction times and thicker gray matter in temporal and frontal cortical areas. However, no direct evidence exists that links individual neuron activity and structure to human intelligence. Since a large part of cortical grey matter consists of dendrites, these structures likely determine cortical architecture. In addition, dendrites strongly affect functional properties of neurons, including action potential speed. Thereby, dendritic size and action potential firing may constitute variation in cortical thickness, processing speed, and ultimately IQ.To investigate this, we took advantage of brain tissue available from neurosurgery and recorded from pyramidal neurons in the medial temporal cortex, an area showing high association between cortical thickness, cortical activity and intelligence. Next, we reconstructed full dendritic structures of recorded neurons and combined these with brain-imaging data and IQ scores from the same subjects. We find that high IQ scores and large temporal cortical thickness associate with larger, more complex dendrites of human pyramidal neurons. We show in silico that larger dendrites enable pyramidal neurons to track activity of synaptic inputs with higher temporal precision, due to fast action potential initiation. Finally, we find that human pyramidal neurons of individuals with higher IQ scores sustain faster action potentials during repeated firing. These findings provide first evidence that human intelligence is associated with neuronal complexity, action potential speed and efficient information transfer in cortical neurons.
Quantitative proteomics identification of seminal fluid proteins in male Drosophila melanogaster
Authors: Sepil Irem , Hopkins Ben R , Dean Rebecca , ThÃ©zÃ©nas Marie-LaÃ«titia , Charles Philip D , Konietzny Rebecca , Fischer Roman , Kessler Benedikt M , Wigby Stuart 
Published: April 2018

AbstractSeminal fluid contains some of the fastest evolving proteins currently known. These seminal fluid proteins (Sfps) play crucial roles in reproduction, such as supporting sperm function, and – particularly in insects – modifying female physiology and behaviour. Identification of Sfps in small animals is challenging, and often relies on samples taken from the female reproductive tract after mating. A key pitfall of this method is that it might miss Sfps that are of low abundance due to dilution in the female-derived sample or rapid processing in females. Here we present a new and complimentary method, which provides added sensitivity to Sfp identification. We applied label-free quantitative proteomics to Drosophila melanogaster male reproductive tissue – where Sfps are unprocessed, and highly abundant – and quantified Sfps before and immediately after mating, to infer those transferred during copulation. We also analysed female reproductive tracts immediately before and after copulation to confirm the presence and abundance of known and candidate Sfps, where possible. Results were cross-referenced with transcriptomic and sequence databases to improve confidence in Sfp detection. Our data was consistent with 124 previously reported Sfps. We found 8 high-confidence novel candidate Sfps, which were both depleted in mated versus unmated males and identified within the reproductive tract of mated but not virgin females. We also identified 31 more candidates that are likely Sfps based on their abundance, known expression and predicted characteristics, and revealed that four proteins previously identified as Sfps are at best minor contributors to the ejaculate. The estimated copy numbers for our candidate Sfps were lower than for previously identified Sfps, supporting the idea that our technique provides a deeper analysis of the Sfp proteome than previous studies. Our results demonstrate a novel, high-sensitivity approach to the analysis of seminal fluid proteomes, whose application will further our understanding of reproductive biology.
Response of the multiple-demand network during simple stimulus discriminations
Authors: Wen Tanya , Mitchell Daniel J , Duncan John 
Published: April 2018

AbstractThe multiple-demand (MD) network is sensitive to many aspects of task difficulty, including such factors as rule complexity, memory load, attentional switching and inhibition. Many accounts link MD activity to top-down task control, raising the question of response when performance is limited by the quality of sensory input, and indeed, some prior results suggest little effect of sensory manipulations. Here we examined judgments of motion direction, manipulating difficulty by either motion coherence or salience of irrelevant dots. We manipulated each difficulty type across six levels, from very easy to very hard, and additionally manipulated whether difficulty level was blocked, and thus known in advance, or randomized. Despite the very large manipulations employed, difficulty had little effect on MD activity, especially for the coherence manipulation. Contrasting with these small or absent effects, we observed the usual increase of MD activity with increased rule complexity. We suggest that, for simple sensory discriminations, it may be impossible to compensate for reduced stimulus information by increased top-down control.
Golgi Renaissance: the pivotal role of the largest Golgi protein giantin
Authors: Casey Carol A. , Thomes Paul , Manca Sonia , Riethoven Jean-Jack M. , Clarke Jennifer , Petrosyan Armen 
Published: April 2018

AbstractGolgi undergoes disorganization in response to the drugs or alcohol, but it is able to restore compact structure under recovery. This self-organization mechanism remains mostly elusive, as does the role of giantin, the largest Golgi matrix dimeric protein. Here, we found that in cells treated with Brefeldin A (BFA) or ethanol (EtOH), Golgi disassembly is associated with giantin de-dimerization, which was restored to the dimer form after BFA or EtOH washout. Cells lacking giantin are disabled for the restoration of the classical ribbon Golgi, and they demonstrate altered trafficking of proteins to the cell surface. The fusion of the nascent Golgi membranes is mediated by the cross-membrane interaction of Rab6a GTPase and giantin. Giantin is involved in the formation of long intercisternal connections, which in giantin-depleted cells was replaced by the short bridges that formed via oligomerization of GRASP65. This phenomenon occurs in advanced prostate cancer cells, in which a fragmented Golgi phenotype is maintained by the dimerization of GRASP65. Thus, we provide a model of Golgi Renaissance, which is impaired in aggressive prostate cancer.
Epigenetic Age-Predictor for Mice based on Three CpG Sites
Authors: Han Yang , Eipel Monika , Sakk Vadim , Dethmers-Ausema Bertien , de Haan Gerald , Geiger Hartmut , Wagner Wolfgang 
Published: April 2018

SummaryEpigenetic clocks for mice were generated based on deep-sequencing analysis of the methylome. In this study we demonstrate that site-specific analysis of DNA methylation levels by pyrosequencing at only three CG dinucleotides (CpGs) in the genes Prima1, Hsf4, and Kcns1 facilitates precise estimation of chronological age in murine blood samples, too. DBA/2J mice revealed accelerated epigenetic aging as compared to C57BL6 mice, which is in line with their shorter life-expectancy. The three-CpG-predictor provides a simple and cost-effective biomarker to determine biological age in large intervention studies with mice.
Synaptobrevin-2 C-terminal Flexible Region Regulates the Discharge of Catecholamine through the Fusion Pore
Authors: Weiss Annita N. 
Published: April 2018

AbstractThe discharge of neurotransmitters from vesicles is a regulated process. Synaptobrevin-2 a SNARE protein, participates in this process through its interaction with other SNARE and associate proteins. Synaptobrevin-2 transmembrane domain is embedded into the vesicle lipid bilayer except for its last three residues. These residues are hydrophilic and constitute synaptobrevin-2 C-terminal flexible region. This region interacts with the intravesicular lipid bilayer phosphate head groups to initiate the fusion pore formation. Here it is shown that, this region also modulates the intravesicular membrane potential thereby the discharged of catecholamine. Synapotobrevin-2 Y113 residue was mutated to lysine or glutamate. The effects of these mutations on the exocytotic process in chromaffin cells were assessed using capacitance measurements, combined with amperometry and stimulation by flash photolysis of caged Ca2+. Both Y113E and Y113K mutations reduced the amplitudes of vesicle fusions and reduced the rates of release of catecholamine molecules in quanta release events. Further investigation revealed that the proximity of these charged residues near the vesicle lipid bilayer most likely changed the intravesicular potential, thereby slowing the flux of ions through the fusion pore, hence reducing the rate of catecholamine secretion. These results suggest that catecholamine efflux is couple with the intravesicular membrane potential.
Ref-1/APE1 inhibition with novel small molecules blocks ocular neovascularization
Authors: Pran Babu Sardar Pasha Sheik , Sishtla Kamakshi , Sulaiman Rania S. , Park Bomina , Shetty Trupti , Shah Fenil , Fishel Melissa L. , Wikel James H. , Kelley Mark R. , Corson Timothy W. 
Published: April 2018

AbstractOcular neovascular diseases like wet age-related macular degeneration are a major cause of blindness. Novel therapies are greatly needed for these diseases. One appealing antiangiogenic target is reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1). This protein can act as a redox-sensitive transcriptional activator for NF-κB and other pro-angiogenic transcription factors. An existing inhibitor of Ref-1’s function, APX3330, previously showed antiangiogenic effects. Here, we developed improved APX3330 derivatives and assessed their antiangiogenic activity. We synthesized APX2009 and APX2014 and demonstrated enhanced inhibition of Ref-1 function in a DNA-binding assay compared to APX3330. Both compounds were antiproliferative against human retinal microvascular endothelial cells (HRECs; GI50 APX2009: 1.1 μM, APX2014: 110 nM) and macaque choroidal endothelial cells (Rf/6a GI50APX2009: 26 μM, APX2014: 5.0 μM). Both compounds significantly reduced the ability of HRECs and Rf/6a cells to form tubes at mid nanomolar concentrations compared to control, and both significantly inhibited HREC and Rf/6a cell migration in a scratch wound assay, reducing NF-κB activation and downstream targets.Ex vivo, both APX2009 and APX2014 inhibited choroidal sprouting at low micromolar and high nanomolar concentrations respectively. In the laser-induced choroidal neovascularization mouse model, intraperitoneal APX2009 treatment significantly decreased lesion volume by 4-fold compared to vehicle (p< 0.0001, ANOVA with Dunnett’s post hoc tests), without obvious intraocular or systemic toxicity. Thus, Ref-1 inhibition with APX2009 and APX2014 blocks ocular angiogenesisin vitroandex vivo, and APX2009 is an effective systemic therapy for CNVin vivo, establishing Ref-1 inhibition as a promising therapeutic approach for ocular neovascularization.
Single-Cell Transcriptomic Analysis of Human Lung Reveals Complex Multicellular Changes During Pulmonary Fibrosis
Authors: Reyfman Paul A. , Walter James M. , Joshi Nikita , Anekalla Kishore R. , McQuattie-Pimentel Alexandra C. , Chiu Stephen , Fernandez Ramiro , Akbarpour Mahzad , Chen Ching-I , Ren Ziyou , Verma Rohan , Abdala-Valencia Hiam , Nam Kiwon , Chi Monica , Han SeungHye , Gonzalez-Gonzalez Francisco J. , Soberanes Saul , Watanabe Satoshi , Williams Kinola J.N. , Flozak Annette S , Nicholson Trevor T. , Morgan Vince K. , Hrusch Cara L. , Guzy Robert D. , Bonham Catherine A. , Sperling Anne I. , Bag Remzi , Hamanaka Robert B. , Mutlu Gökhan M. , Yeldandi Anjana V. , Marshall Stacy A. , Shilatifard Ali , Amaral Luis A.N. , Perlman Harris , Sznajder Jacob I. , Winter Deborah R. , Hinchcliff Monique , Argento A. Christine , Gillespie Colin T. , D’Amico Dematte Jane , Jain Manu , Singer Benjamin D. , Ridge Karen M. , Gottardi Cara J. , Lam Anna P. , Bharat Ankit , Bhorade Sangeeta M. , Budinger G.R. Scott , Misharin Alexander V. 
Published: April 2018

AbstractPulmonary fibrosis is a devastating disorder that results in the progressive replacement of normal lung tissue with fibrotic scar. Available therapies slow disease progression, but most patients go on to die or require lung transplantation. Single-cell RNA-seq is a powerful tool that can reveal cellular identity via analysis of the transcriptome, but its ability to provide biologically or clinically meaningful insights in a disease context is largely unexplored. Accordingly, we performed single-cell RNA-seq on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and one bronchoscopic cryobiospy sample. Integrated single-cell transcriptomic analysis of donors and patients with pulmonary fibrosis identified the emergence of distinct populations of epithelial cells and macrophages that were common to all patients with lung fibrosis. Analysis of transcripts in the Wnt pathway suggested that within the same cell type, Wnt secretion and response are restricted to distinct non-overlapping cells, which was confirmed using in situ RNA hybridization. Single-cell RNA-seq revealed heterogeneity within alveolar macrophages from individual patients, which was confirmed by immunohistochemistry. These results support the feasibility of discovery-based approaches applying next generation sequencing technologies to clinically obtained samples with a goal of developing personalized therapies.One Sentence SummarySingle-cell RNA-seq applied to tissue from diseased and donor lungs and a living patient with pulmonary fibrosis identifies cell type-specific disease-associated molecular pathways.
Transient protein accumulation at the center of the T cell antigen presenting cell interface drives efficient IL-2 secretion
Authors: Clark Danielle J. , McMillan Laura E. , Tan Sin Lih , Bellomo Gaia , Massoué Clémentine , Thompson Harry , Mykhaylechko Lidiya , Alibhai Dominic , Ruan Xiongtao , Singleton Kentner L. , Du Minna , Hedges Alan J. , Schwartzberg Pamela L. , Verkade Paul , Murphy Robert F. , Wülfing Christoph 
Published: April 2018

AbstractSupramolecular signaling assemblies are of interest for their unique signaling properties. A µm scale signaling assembly, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen presenting cells. We have determined that it is composed of multiple complexes of a supramolecular volume of up to 0.5µm3 and associated with extensive membrane undulations. To determine cSMAC function, we have systematically manipulated the localization of three adaptor proteins, LAT, SLP-76, and Grb2. cSMAC localization varied between the adaptors and was diminished upon blockade of the costimulatory receptor CD28 and deficiency of the signal amplifying kinase Itk. Reconstitution of cSMAC localization restored IL-2 secretion which is a key T cell effector function as dependent on reconstitution dynamics. Our data suggest that the cSMAC enhances early signaling by facilitating signaling interactions and attenuates signaling thereafter through sequestration of a more limited set of signaling intermediates.
Hybridization, sex specific genomic architecture and local adaptation
Authors: Runemark Anna , Eroukhmanoff Fabrice , Nava-Bolaños Angela , Hermansen Jo S , Meier Joana I 
Published: April 2018

AbstractWhile gene flow can reduce the potential for local adaptation, hybridization may conversely provide genetic variation that increases the potential for local adaptation. Hybridization may also affect adaptation through altering sexual dimorphism and sexual conflict, but this remains largely unstudied. Here, we discuss how hybridization may affect sexual dimorphism and conflict due to differential effects of hybridization on males and females, and then how this in turn may affect local adaptation. First, the lower viability of the heterogametic sex in hybrids could shift the balance in sexual conflict. Second, sex-specific inheritance of the mitochondrial genome in hybrids may lead to cyto-nuclear mismatches, for example in the form of “mother’s curse”, with potential consequences for sex-ratio and sex specific expression. Third, transgressive segregation of sexually antagonistic alleles could lead to greater sexual dimorphism in hybrid populations. These mechanisms can reduce sexual conflict and enhance intersexual niche partitioning, increasing the fitness of hybrids. Adaptive introgression of alleles reducing sexual conflict or enhancing intersexual niche partitioning may facilitate local adaptation, and could favour the colonization of novel habitats. We review these consequences of hybridization on sex differences and local adaptation, and discuss how their prevalence and importance could be tested empirically.
Organizing neuronal ER-PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels
Authors: Kirmiz Michael , Palacio Stephanie , Thapa Parashar , King Anna N. , Sack Jon T. , Trimmer James S. 
Published: April 2018

AbstractEndoplasmic reticulum (ER) and plasma membrane (PM) form junctions crucial to ion and lipid signaling and homeostasis. The Kv2.1 ion channel is unique among PM proteins in organizing ER-PM junctions. Here, we show that this organizing function is conserved between Kv2 family members that differ in their biophysical properties, modulation and cellular expression. Manipulation of actin cytoskeleton surrounding Kv2 ER-PM junctions affects their spatial organization. Kv2-containing ER-PM junctions overlap with those formed by canonical ER-PM tethers. ER-PM junction organization by Kv2 channels is unchanged by point mutations that eliminate ion conduction, but abolished by those that eliminate PM clustering without impacting ion channel function. Kv2.2 is distinct in lacking the reversible modulation of junction organization present in Kv2.1. Brain neurons in Kv2 double knockout mice have altered ER-PM junctions, demonstrating a conserved in vivo function for Kv2 family members distinct from their canonical role as ion-conducting channels shaping neuronal excitability.
Maternal tamoxifen treatment expands the macrophage population of early mouse embryos
Authors: Rojo Rocío , Sauter Kristin A. , Lefevre Lucas , Hume David A. , Pridans Clare 
Published: April 2018

AbstractSeveral different transgenic tamoxifen-inducible cre reporter lines have been used to analyse the contribution of embryonic precursors to the development of the mononuclear phagocyte system in mice. Here we show that tamoxifen treatment of the mother at 8.5dpc with doses commonly-used in lineage trace studies produces a 4-5-fold expansion of the embryonic leukocyte populations by 10.5dpc, detected in whole mounts of embryos using aCsf1rreporter gene or separately by expression ofCsf1r, Itgam(CD11b),Adgre1(F4/80) orPtprc(CD45) mRNA. These findings indicate that tamoxifen cannot be considered a neutral agonist in macrophage lineage trace studies.Summary sentenceTreatment of pregnant mice with tamoxifen in early gestation produces a large expansion of the embryonic macrophage population.