bluuebunny/crossref_metadata_2025_split huggingface dataset:
Live calcium imaging ofAedes aegyptineuronal tissues reveals differential importance of chemosensory systems for life-history-specific foraging strategies
Authors: Bui Michelle , Shyong Jennifer , Lutz Eleanor K. , Yang Ting , Li Ming , Truong Kenneth , Arvidson Ryan , Buchman Anna , Riffell Jeffrey A. , Akbari Omar S. 
Published: June 2018

AbstractAedes aegyptihave a wide variety of sensory pathways that have supported success as a species as well as a highly competent vector of numerous debilitating infectious pathogens. Investigations into mosquito sensory systems and their effects on behavior are valuable resources for the advancement of mosquito control strategies. Numerous studies have elucidated key aspects of mosquito sensory systems, however there remains critical gaps within the field. In particular, compared to that of the adult form, there has been a lack of studies directed towards the immature life stages. Additionally, although numerous studies have pinpointed specific sensory receptors as well as relevant response behaviors, there has been a lack of studies able to monitor both concurrently. To begin filling aforementioned gaps, here we engineeredAe. aegyptito ubiquitously express a genetically encoded calcium indicator, GCaMP6s. Using this strain, combined with advanced confocal microscopy, we were able to simultaneously measure live stimulus-evoked calcium responses in both neuronal and muscle cells with a wide spatial range and resolution. Moreover, by couplingin vivocalcium imaging with behavioral assays we were able to gain functional insights into how stimulus-evoked neural and muscle activities are represented, modulated, and transformed in mosquito larvae enabling us to elucidate mosquito sensorimotor properties important for life-history-specific foraging strategies.Significance StatementUnderstanding mosquito sensory systems and resulting behavior has been a major factor in the advancement of mosquito control innovations.Aedes aegyptilarvae offer an effective life stage for further elucidating information on mosquito sensory systems. Due to their relatively simplified nervous system, mosquito larvae are ideal for studying neural signal transduction, coding, and behavior. Moreover, a better understanding of the larval sensory system may enable the development of novel control methodologies able to target mosquitoes before they reach a vector-competent stage. Here we engineerAe. aegyptito ubiquitously express a genetically encoded calcium indicator, GCaMP6s and use this tool to observe links between sensorimotor responses and behavior by exploiting live calcium imaging as well as live tracking based behavioral assays.
Sexual Conflict through Mother’s Curse and Father’s Curse
Authors: Arvid Ågren J. , Munasinghe Manisha , Clark Andrew G. 
Published: June 2018

AbstractIn contrast with autosomes, lineages of sex chromosomes reside for different amounts of time in males and females, and this transmission asymmetry makes them hotspots for sexual conflict. Similarly, the maternal inheritance of the mitochondrial genome (mtDNA) means that mutations that are beneficial in females can spread in a population even if they are deleterious in males, a form of sexual conflict known as Mother’s Curse. While both Mother’s Curse and sex chromosome induced sexual conflict have been well studied on their own, the interaction between mitochondrial genes and genes on sex chromosomes is poorly understood. Here, we use analytical models and computer simulations to perform a comprehensive examination of how transmission asymmetries of nuclear, mitochondrial, and sex chromosome-linked genes may both cause and resolve sexual conflicts. For example, the accumulation of male-biased Mother’s Curse mtDNA mutations will lead to selection in males for compensatory nuclear modifier loci that alleviate the effect. We show how the Y chromosome, being strictly paternally transmitted provides a particularly safe harbor for such modifiers. This analytical framework also allows us to discover a novel kind of sexual conflict, by which Y chromosome-autosome epistasis may result in the spread of male beneficial but female deleterious mutations in a population. We christen this phenomenon Father’s Curse. Extending this analytical framework to ZW sex chromosome systems, where males are the heterogametic sex, we also show how W-autosome epistasis can lead to a novel kind of nuclear Mother’s Curse. Overall, this study provides a comprehensive framework to understand how genetic transmission asymmetries may both cause and resolve sexual conflicts.
CRISPR-SURF: Discovering regulatory elements by deconvolution of CRISPR tiling screen data
Authors: Hsu Jonathan Y. , Fulco Charles P. , Cole Mitchel A. , Canver Matthew C. , Pellin Danilo , Sher Falak , Farouni Rick , Clement Kendell , Guo James A. , Biasco Luca , Orkin Stuart H. , Engreitz Jesse M. , Lander Eric S. , Keith Joung J. , Bauer Daniel E. , Pinello Luca 
Published: June 2018

AbstractTiling screens using CRISPR-Cas technologies provide a powerful approach to map regulatory elements to phenotypes of interest, but computational methods that effectively model these experimental approaches for different CRISPR technologies are not readily available. Here we present CRISPR-SURF, a deconvolution framework to identify functional regulatory regions in the genome from data generated by CRISPR-Cas nuclease, CRISPR interference (CRISPRi), or CRISPR activation (CRISPRa) tiling screens. We validated CRISPR-SURF on previously published and new data, identifying both experimentally validated and new potential regulatory elements. With CRISPR tiling screens now being increasingly used to elucidate the regulatory architecture of the non-coding genome, CRISPRSURF provides a generalizable and accessible solution for the discovery of regulatory elements.
Breaking the “unbreakable” ZIKA virus envelope
Authors: Pindi Chinmai , Chirasani Venkat R , Homaidur Rahman Mohd. , Ahsan Mohd. , Revanasiddappa Prasanna D , Senapati Sanjib 
Published: June 2018

ABSTRACTThe rapid spread of zika virus (ZIKV) and its association with microcephaly and Guillain-Barre syndrome have raised major concerns worldwide. Studies have shown that ZIKV can survive in harsh conditions, e.g. high fever; in sharp contrast to the dengue virus (DENV) of same Flaviviridae family. In spite of recent cryo-EM structures that showed similar architecture of the ZIKV and DENV envelopes, little is known of what makes ZIKV envelope so robust and unique. Here, we present a detailed analysis of the constituent raft-raft and protein-protein interactions on ZIKV and DENV envelopes to undermine their differential stability at near-atomic to atomic level using coarse-grained (CG) and all-atom (AA) molecular dynamics simulations. Our results from CG simulations show that, at high temperatures, ZIKV envelope retains its structural integrity, while DENV2 disintegrate through the formation of holes at 5- and 3-fold vertices. Protein structural network from AA simulations shows a stronger inter-raft communications in ZIKV through multiple electrostatic and H-bond interactions. Particularly, the intricate network of interlocking DE-loop and FG-loop among five DIII domains in ZIKA vertices was exceedingly robust that makes this envelope stable, even at high temperatures. Our results are validated by alanine mutations to the CD-loop residues Gln350 and Thr351 that showed no effect on ZIKA stability, in close accordance with a recent mutagenesis study. These detailed information, which were difficult to extract experimentally, broadened our understanding of the flaviviruses and can accelerate the structure-based drug designing processes aiming ZIKA and DENV therapeutics.IMPORTANCEThe rapid spread of zika virus (ZIKV) and its association with severe birth defects have raised worldwide concern. Recent studies have shown that ZIKV can survive in harsh conditions, e.g. high fever, unlike dengue (DENV) and other flaviviruses. Here, we unravel the molecular basis of ZIKV unprecedented stability over DENV at high temperatures, mimicking fever. Our study, based on coarse-grained and all-atom molecular dynamics simulations, could not only explore the mechanism of DENV envelope breaking at high temperatures, but also captured atomic-level contacts and interactions at raft-raft and protein-protein interfaces that keep ZIKV envelope intact in similar conditions. The obtained results are validated by in-silico and reported in-vitro mutagenesis studies by showing the presence of specific H-bonding and electrostatic interactions among ZIKV E protein residues. At the end, our study was successful to define potential ZIKV epitopes and provide residue-level insights for designing specific ZIKV antibodies and small molecule inhibitors.
Sam50-Mic19-Mic60 axis Determines Mitochondrial Cristae Architecture by Mediating Mitochondrial Outer and Inner Membrane Contact
Authors: Tang Junhui , Zhang Kuan , Dong Jun , Yan Chaojun , Chen Shi , Song Zhiyin 
Published: June 2018

ABSTRACTMitochondrial cristae are critical for efficient oxidative phosphorylation, however, how cristae architecture is precisely organized remains largely unknown. Here, we discovered that Mic19, a core component of MICOS (mitochondrial contact site and cristae organizing system) complex, can be cleaved at N-terminal by mitochondrial protease OMA1. Mic19 directly interacts with mitochondrial outer-membrane protein Sam50 (the key subunit of SAM complex) and inner-membrane protein Mic60 (the key component of MICOS complex) to form Sam50-Mic19-Mic60 axis, which dominantly connects SAM and MICOS complexes to assemble MIB (mitochondrial intermembrane space bridging) supercomplex for mediating mitochondrial outer- and inner-membrane contact. OMA1-mediated Mic19 cleavage causes Sam50-Mic19-Mic60 axis disruption, which separates SAM and MICOS and leads to MIB disassembly. Disrupted Sam50-Mic19-Mic60 axis, even in the presence of SAM and MICOS complexes, causes the abnormal mitochondrial morphology, loss of mitochondrial cristae junctions, abnormal cristae distribution and reduced ATP production. Importantly, Sam50 displays punctate distribution at mitochondrial outer membrane, and acts as an anchoring point to guide the formation of mitochondrial cristae junctions. Therefore, we propose a model that Sam50-Mic19-Mic60 axis mediated SAM-MICOS complexes integration determines mitochondrial cristae architecture.
Environmental enrichment in piglet creeps: behavior and productive performance
Authors: Sartor Karina , de Freitas Bolivar Felipe , de Souza Granja Barros Juliana , Rossi Luiz Antonio 
Published: June 2018

AbstractIn the farrowing stage, to use heated creeps is crucial for meeting the thermal requirements of newborn piglets and alternatives for environmental enrichment to attract the animals to the creeps. The objective of this study was to evaluate the behavior and productive performance of piglets submitted to creeps enriched with different types of sensory stimuli. The study had a completely randomized design. The animals were submitted to seven treatments: T1) Enrichment with blue LED lighting; T2) Enrichment with fragrance of chamomile (Matricaria chamomilla) essential oil; T3) Enrichment with fragrance of lavender (Lavandula) essential oil; T4) Enrichment with fragrance of lemon (Citrus × latifolia) essential oil; T5) Enrichment with classical music, “The Four Seasons” by Vivaldi; T6) Creeps heated without environmental enrichment (control group); T7) Enrichment with fragrance of thyme (Thymus vulgaris) essential oil. The piglets were submitted to creeps with environmental enrichment under automatic control every 15 min (on/off), from 8 am to 5:45 pm (21 consecutive days). The environmental conditions of the creeps – air temperature, relative humidity, luminous intensity, and decibels – were evaluated within the creeps with environmental enrichment to determine the influence on the piglets’ behavior and productive performance. The results show that piglets submitted to creeps with environmental enrichment with blue artificial light and thyme essential oil showed reduced frequency outside the creeps when compared with treatment T6 (control). This showed the reduction of the stay of piglets in areas susceptible to crushing, in proximities to the mother. Piglets showed greater preference for creeps enriched with fragrance diffusion of thyme essential oil and with blue artificial lighting.
Learning the payoffs and costs of actions
Authors: Möller Moritz , Bogacz Rafal 
Published: June 2018

AbstractA set of sub-cortical nuclei called basal ganglia is critical for learning the values of actions. The basal ganglia include two pathways, which have been associated with approach and avoid behavior respectively, and are differentially modulated by dopamine projections from the midbrain. According to the influential opponent actor learning model, these pathways represent learned estimates of the positive and negative consequences (payoffs and costs) of actions. The level of dopamine release controls to what extent payoffs and costs enter the overall evaluation of actions. How the knowledge about payoff and cost is acquired is still an open question, even though many theories describe learning from feedback in the basal ganglia. We examine whether a set of plasticity rules proposed to model reinforcement learning in the pathways of the basal ganglia is suitable to extract payoffs and costs from a reward prediction error signal. First, we determine the result of such learning, both analytically and via simulations, for different reward schedules that feature payoffs and costs. Then, we combine the plasticity rules with a decision rule to examine the emerging effect of dopaminergic modulation on the willingness to work for reward. We find that the plasticity rules are suitable to infer the mean payoffs and costs of actions, if those occur at different moments in time. Successful learning requires differential effects of positive and negative reward prediction errors on the two pathways, and a weak decay of synaptic weights over trials. We also confirm that dopaminergic modulation produces effects on the willingness to work for reward similar to those observed in classical experiments.Author summaryThe basal ganglia are structures underneath the surface of the vertebrate brain, associated with error driven learning. Much is known about the anatomical and biological features of the basal ganglia; scientists now try to understand the algorithms implemented by these structures. Numerous models aspire to capture the learning functionality, but many of them only cover some specific aspect of the algorithm. Instead of further adding to that pool of partial models, we unify two existing ones - one which captures what the basal ganglia learns, and one that describes the learning mechanism itself. The first model suggests that the basal ganglia keeps track of both positive and negative consequences of frequent opportunities, and weighs these by the motivational state in decisions. It explains how payoff and cost are represented, but not how those representations arise. The other model consists of biologically plausible plasticity rules, which describe how learning takes place, but not how the brain makes use of what is learned. We show that the two theories are compatible. Together, they form a model of learning and decision making that integrates the motivational state as well as the learned payoffs and costs of opportunities.
Broad applicability of a streamlined Ethyl Cinnamate-based clearing procedure
Authors: Masselink Wouter , Reumann Daniel , Murawala Prayag , Pasierbek Pawel , Taniguchi Yuka , Knoblich Jürgen A. , Tanaka Elly M. 
Published: June 2018

AbstractTurbidity and opaqueness are inherent properties of tissues which limit the capacity to acquire microscopic images through large tissues. Creating a uniform refractive index, known as tissue clearing, overcomes most of these issues. These methods have enabled researchers to image large and complex 3D structures with unprecedented depth and resolution. However, tissue clearing has been adopted to a limited extent due to a combination of cost, time, complexity of existing methods and potential negative impact on fluorescence signal. Here we describe 2Eci (2nd generation Ethyl cinnamate based clearing method) which can be used to clear a wide range of tissues, including cerebral organoids, Drosophila melanogaster, zebrafish, axolotl, and Xenopus laevis in as little as 1-5 days while preserving a broad range of fluorescence proteins including GFP, mCherry, Brainbow, and alexa-fluorophores. Ethyl cinnamate is non-toxic and can easily be used in multi-user microscope facilities. This method will open up clearing to a much broader group of researchers, due to its broad applicability, ease of use, and non-toxic nature of Ethyl cinnamate.Summary statementThe non-toxic, broadly applicable, and simplified protocol of 2Eci tissue clearing makes it possible for non-specialist labs to use clearing approaches on conventional inverted microscopes.
Production of alkanes from CO2 by engineered bacteria
Authors: Lehtinen Tapio , Virtanen Henri , Santala Suvi , Santala Ville 
Published: June 2018

AbstractBackgroundMicrobial biosynthesis of alkanes is considered a promising method for the sustainable production of drop-in fuels and chemicals. Carbon dioxide would be an ideal carbon source for these production systems, but efficient production of long carbon chains from CO2is difficult to achieve in a single organism. A potential solution is to employ acetogenic bacteria for the reduction of CO2to acetate, and engineer a second organism to convert the acetate into long-chain hydrocarbons.ResultsIn this study, we demonstrate alkane production from CO2by a system combining the acetogenAcetobacterium woodiiand a non-native alkane producerAcinetobacter baylyiADP1 engineered for alkane production. Nine synthetic two-step alkane biosynthesis pathways consisting of different aldehyde- and alkane-producing enzymes were combinatorically constructed and expressed inA. baylyi.The aldehyde-producing enzymes studied were AAR fromSynechococcus elongatus,Acr1 fromA. baylyi,and Ramo, a putative dehydrogenase, fromNevskia ramosa.The alkane-producing enzymes were ADOs fromS. elongatusandNostoc punctiforme,and CER1 fromArabidopsis thaliana.The performance of the pathways was evaluated with a twin-layer biosensor, which allowed the monitoring of both the intermediate, fatty aldehyde, as well as the alkane production. The highest alkane production, as indicated by the biosensor, was achieved with a pathway consisting of AAR and ADO fromS. elongatus.The performance of this pathway was further improved by balancing the relative expression levels of the enzymes in order to limit the accumulation of the intermediate fatty aldehyde. Finally, the acetogenA. woodiiwas used to produce acetate from CO2and H2, and the acetate was used for alkane production by the engineeredA. baylyi,thereby leading to the net production of long-chain alkanes from CO2.ConclusionsA modular system for the production of drop-in liquid fuels from CO2was demonstrated. Among the studied synthetic pathways, the combination of ADO and AAR fromS. elongatuswas found to be the most efficient in heterologous alkane production inA. baylyi.Furthermore, limiting the accumulation of the fatty aldehyde intermediate was found to be beneficial for the alkane production.
Prognostic Relevance of CCDC88C (Daple) Transcripts in the Peripheral Blood of Patients with Malignant Melanoma
Authors: Dunkel Ying , Reid Anna L. , Ear Jason , Aznar Nicolas , Millward Michael , Gray Elin , Pearce Robert , Ziman Melanie , Ghosh Pradipta 
Published: June 2018

AbstractA loss of balance between G-protein activation and deactivation has been implicated in the initiation of melanomas, and non-canonical Wnt signaling via the Wnt5A/Frizzled (FZD) pathway has been shown to be critical for the switch to an invasive phenotype. Daple [CCDC88C gene], a cytosolic guanine nucleotide exchange factor (GEF) which enhances non-canonical Wnt5A/FZD signaling via activation of trimeric G protein, Gai has been shown to serve opposing roles-- as an inducer of EMT and invasiveness and a potent tumor suppressor -- via two isoforms, V1 (full-length) and V2, respectively. Here we report that the relative abundance of these isoforms in the peripheral circulation, presumably largely from circulating tumor cells (CTCs), is a prognostic marker of cutaneous melanomas. Expression of V1 is increased in both the early and late clinical stages (p<0.001, p=0.002, respectively); V2 is decreased exclusively in the late clinical stage (p=0.011). The two isoforms have opposing prognostic effects: high expression of V2 increases progression-free survival (PFS; p = 0.02), whereas high expression of V1 decreases PFS (p=0.013). Furthermore, these effects are additive, in that melanoma patients with a low V2-high V1 signature carry the highest risk of metastatic disease. We conclude that detection of Daple transcripts in the peripheral blood (i.e., liquid biopsies) of patients with melanoma may serve as a prognostic marker and an effective strategy for non-invasive long-term follow-up of patients with melanoma.
Auxin Efflux Carrier ZmPGP1 Mediates Root Growth Inhibition under Aluminum Stress
Authors: Zhang Maolin , Lu Xiaoduo , Li Cuiling , Zhang Bing , Zhang Chunyi , Zhang Xian-sheng , Ding Zhaojun 
Published: June 2018

Abstract
Auxin has been shown to enhance root growth inhibition under aluminum (Al) stress in Arabidopsis (Arabidopsis thaliana). However, in maize (Zea mays), auxin may play a negative role in the Al-induced inhibition of root growth. In this study, we identified mutants deficient in the maize auxin efflux carrier P-glycoprotein (ZmPGP1) after ethyl methanesulfonate mutagenesis and used them to elucidate the contribution of ZmPGP1 to Al-induced root growth inhibition. Root growth in the zmpgp1 mutant, which forms shortened roots and is hyposensitive to auxin, was less inhibited by Al stress than that in the inbred line B73. In the zmpgp1 mutants, the root tips displayed higher auxin accumulation and enhanced auxin signaling under Al stress, which was also consistent with the increased expression of auxin-responsive genes. Based on the behavior of the auxin-responsive marker transgene, DR5rev:RFP, we concluded that Al stress reduced the level of auxin in the root tip, which contrasts with the tendency of Al stress-induced Arabidopsis plants to accumulate more auxin in their root tips. In addition, Al stress induced the expression of ZmPGP1. Therefore, in maize, Al stress is associated with reduced auxin accumulation in root tips, a process that is regulated by ZmPGP1 and thus causes inhibition of root growth. This study provides further evidence about the role of auxin and auxin polar transport in Al-induced root growth regulation in maize.