bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spaced training forms complementary long-term memories of opposite valence inDrosophila
Authors: Jacob Pedro F. , Waddell Scott 
Published: September 2019

AbstractForming long-term memory (LTM) in many cases requires repetitive experience spread over time. InDrosophila, aversive olfactory LTM is optimal following spaced training, multiple trials of differential odor conditioning with rest intervals. Studies often compare memory after spaced to that after massed training, same number of trials without interval. Here we show flies acquire additional information after spaced training, forming an aversive memory for the shock-paired odor and a ‘safety-memory’ for the explicitly unpaired odor. Safety-memory requires repetition, order and spacing of the training trials and relies on specific subsets of rewarding dopaminergic neurons. Co-existence of the aversive and safety memories can be measured as depression of odor-specific responses at different combinations of junctions in the mushroom body output network. Combining two particular outputs appears to signal relative safety. Learning a complementary safety memory thereby augments LTM performance after spaced training by making the odor preference more certain.
Examining multiple cellular pathways at once using multiplex hextuple luciferase assaying
Authors: Sarrion-Perdigones Alejandro , Chang Lyra , Gonzalez Yezabel , Gallego-Flores Tatiana , Young Damian W. , Venken Koen J.T. 
Published: September 2019

AbstractSensitive simultaneous assessment of multiple signaling pathways within the same cells requires orthogonal reporters that can assay over large dynamic ranges. Luciferases have arisen as possible genetically encoded candidates due to their sensitivity, versatility, and cost-effectiveness. Here, we expanded luciferase multiplexing in post-lysis endpoint luciferase assays from two towards six. Light emissions are distinguished by a combination of distinct substrates and emission spectra deconvolution. Using synthetic assembly cloning, all six luciferase reporter units are stitched together into one plasmid; facilitating delivery of all reporter units through a process we named solotransfection, minimizing experimental errors. We engineered a multiplex hextuple luciferase assay to probe pathway fluxes through five transcriptional response elements against a control constitutive promoter. We were able to monitor the effects of siRNA, ligand, and chemical compound treatments on their target pathways along with the four other probed cellular pathways. We demonstrate the effectiveness and adaptiveness of multiplex luciferase assaying, as well as its broad application across different research fields.
Bacterial DNA promotes Tau aggregation
Authors: Tetz George , Pinho Michelle , Pritzkow Sandra , Mendez Nicolas , Soto Claudio , Tetz Victor 
Published: September 2019

AbstractA hallmark feature of Alzheimer’s disease (AD) and other tauopathies is the misfolding, aggregation and cerebral accumulation of tau deposits. Compelling evidence indicates that misfolded tau aggregates are neurotoxic, producing synaptic loss and neuronal damage. Misfolded tau aggregates are able to spread the pathology from cell-to-cell by a prion like seeding mechanism. The factors implicated in the initiation and progression of tau misfolding and aggregation are largely unclear. In this study, we evaluated the effect of DNA extracted from diverse prokaryotic and eukaryotic cells in tau misfolding and aggregation. Our results show that DNA from various, unrelated gram-positive and gram-negative bacteria results in a more pronounced tau misfolding compared to eukaryotic DNA. Interestingly, a higher effect in promoting tau aggregation was observed for DNA extracted from certain bacterial species previously detected in the brain, CSF or oral cavity of patients with AD. Our findings indicate that microbial DNA may play a previously overlooked role in the propagation of tau protein misfolding and AD pathogenesis, providing a new conceptual framework that positions the compromised blood-brain and intestinal barriers as important sources of microbial DNA in the CNS, opening novel opportunities for therapeutic interventions.
Population differences in how wild Trinidadian guppies use social information and socially learn
Authors: Chouinard-Thuly Laura , Reader Simon M. 
Published: September 2019

AbstractAnimals have access to information produced by the behaviour of other individuals, which they may use (“social information use”) and learn from (“social learning”). The benefits of using such information differ with socio-ecological conditions. Thus, population differences in social information use and social learning should occur. We tested this hypothesis with a comparative study across five wild populations of Trinidadian guppies (Poecilia reticulata) known to differ in their ecology and social behaviour. Using a field experiment, we found population differences in how guppies used and learned from social information, with only fish from one of the three rivers studied showing evidence of social information use and social learning. Within this river, populations differed in how they employed social information: fish from a high-predation regime where guppies exhibit high shoaling propensities chose the same foraging location than conspecifics, while fish from a low-predation regime with reduced shoaling propensities chose and learned the opposite foraging location than conspecifics. We speculate that these differences are due to differences in predation risk and conspecific competition, possibly mediated via changes in grouping tendencies. Our results provide evidence that social information use and social learning can differ across animal populations and are influenced by socio-ecological factors.
ABEL-FRET: tether-free single-molecule FRET with hydrodynamic profiling
Authors: Wilson Hugh , Wang Quan 
Published: September 2019

ABSTRACTSingle-molecule Förster resonance energy transfer (smFRET) has become a versatile and widespread method to probe nanoscale conformation and dynamics. However, current experimental protocols often resort to molecule immobilization for long observation times and rarely approach the resolution limit of FRET-based nanoscale metrology. Here we present ABEL-FRET, an immobilization-free platform for smFRET measurements with near shot-noise limited, Angstrom-level resolution in FRET efficiency. Furthermore, ABEL-FRET naturally integrates hydrodynamic profiling, which harnesses single-molecule diffusion coefficient to enhance FRET sensing of biological processes.
A cell surface arabinogalactan-peptide influences root hair cell fate
Authors: Borassi Cecilia , Dorosz Javier Gloazzo , Ricardi Martiniano M. , Pol Fachin Laercio , Sardoy Mariana Carignani , Marzol Eliana , Mangano Silvina , Rodríguez Garcia Diana Rosa , Martínez Pacheco Javier , del Carmen Rondón Guerrero Yossmayer , Velasquez Silvia M. , Villavicencio Bianca , Ciancia Marina , Seifert Georg , Verli Hugo , Estevez José M. 
Published: September 2019

SummaryRoot hairs (RHs) develop from specialized epidermal cells called trichoblasts, whereas epidermal cells that lack RHs are known as atrichoblasts. The mechanism controlling root epidermal cell fate is only partially understood. Root epidermis cell fate is regulated by a transcription factor complex that promotes the expression of the homeodomain protein GLABRA 2 (GL2), which blocks RH development by inhibiting ROOT HAIR DEFECTIVE 6 (RHD6). Suppression of GL2 expression activates RHD6, a series of downstream TFs including ROOT HAIR DEFECTIVE 6 LIKE-4 (RSL4 [Yi et al. 2010]) and their target genes, and causes epidermal cells to develop into RHs. Brassinosteroids (BRs) influence root epidermis cell fate. In the absence of BRs, phosphorylated BIN2 (a Type-II GSK3-like kinase) inhibits a protein complex that directly downregulates GL2 [Chen et al. 2014]. Here, we show that the genetic and pharmacological perturbation of the arabinogalactan peptide (AG) AGP21 inArabidopsis thaliana, triggers aberrant RH development, similar to that observed in plants with defective BR signaling. We reveal that anO-glycosylated AGP21 peptide, which is positively regulated by BZR1, a transcription factor activated by BR signaling, affects RH cell fate by alteringGL2expression in a BIN2-dependent manner. These results suggest that perturbation of a cell surface AGP disrupts BR responses and inhibits the downstream effect of BIN2 on the RH repressor GL2 in root epidermal cells. In addition, AGP21 also acts in a BR-independent, AGP-dependent mode that together with BIN2 signalling cascade controls RH cell fate.SignificanceIn the plantArabidopsis thaliana, the root epidermis forms in an alternating pattern atrichoblasts with trichoblast cells that end up developing root hairs (RHs). Atrichoblast cell fate is directly promoted by the transcription factor GLABRA2 (GL2) while the lack of GL2 allows RH formation. The loss of AGP21 peptide triggers an abnormal RH cell fate in two contiguous cells in a similar manner as brassinosteroid (BRs) mutants. In the absence of BR signaling, BIN2 (a GSK3 like-kinase) in a phosphorylated state, downregulate GL2 expression to trigger RH cell fate. The absence of AGP21 is able to repressGL2expression and activates the expression of RSL4 and EXP7 root hair proteins.
Quantitative characterization of the path of glucose diffusion facilitated by human glucose transporter 1
Authors: Chen Liao Y. 
Published: September 2019

ABSTRACTGlucose transporter GLUT1 is ubiquitously expressed in the human body from the red cells to the blood-brain barrier to the skeletal muscles. It is physiologically relevant to understand how GLUT1 facilitates diffusion of glucose across the cell membrane. It is also pathologically relevant because GLUT1 deficiency causes neurological disorders and anemia and because GLUT1 overexpression fuels the abnormal growth of cancer cells. This article presents a quantitative investigation of GLUT1 based on all-atom molecular-dynamics (MD) simulations of the transporter embedded in lipid bilayers of asymmetric inner-and-outer-leaflet lipid compositions, subject to asymmetric intra-and-extra-cellular environments. This is in contrast with the current literature of MD studies that have not considered both of the aforementioned asymmetries of the cell membrane. The equilibrium (unbiased) dynamics of GLUT1 shows that it can facilitate glucose diffusion across the cell membrane without undergoing large-scale conformational motions. The Gibbs free-energy profile, which is still lacking in the current literature of GLUT1, quantitatively characterizes the diffusion path of glucose from the periplasm, through an extracellular gate of GLUT1, on to the binding site, and off to the cytoplasm. This transport mechanism is validated by the experimental data that GLUT1 has low water-permeability, uptake-efflux symmetry, and 10 kcal/mol Arrhenius activation barrier around 37°C.GRAPHICAL ABSTRACT (or TABLE OF CONTENTS ENTRY)
C9orf72 arginine-rich dipeptide repeat proteins disrupt importin β-mediated nuclear import
Authors: Hayes Lindsey R. , Duan Lauren , Bowen Kelly , Kalab Petr , Rothstein Jeffrey D. 
Published: September 2019

AbstractDisruption of nucleocytoplasmic transport (NCT), including mislocalization of the importin β cargo, TDP-43, is a hallmark of amyotrophic lateral sclerosis (ALS), including ALS caused by a hexanucleotide repeat expansion in C9orf72. However, the mechanism(s) remain unclear. Importin β and its cargo adaptors have been shown to co-precipitate with the C9orf72-arginine-containing dipeptide repeat proteins (R-DPRs), poly-glycine arginine (GR) and poly-proline arginine (PR), and are protective in genetic modifier screens. Here, we show that R-DPRs interact with importin β, disrupt its cargo loading, and inhibit nuclear import in permeabilized mouse neurons and HeLa cells, in a manner that can be rescued by RNA. Although R-DPRs induce widespread protein aggregation in this in vitro system, transport disruption is not due to NCT protein sequestration, nor blockade of the phenylalanine-glycine (FG)-rich nuclear pore complex. Our results support a model in which R-DPRs interfere with nuclear transport receptors in the vicinity of the nuclear envelope.
Mammalian Y RNAs are modified at discrete guanosine residues with N-glycans
Authors: Flynn Ryan A. , Smith Benjamin A. H. , Johnson Alex G. , Pedram Kayvon , George Benson M. , Malaker Stacy A. , Majzoub Karim , Carette Jan E. , Bertozzi Carolyn R. 
Published: September 2019

ABSTRACTGlycans modify lipids and proteins to mediate inter- and intramolecular interactions across all domains of life. RNA, another multifaceted biopolymer, is not thought to be a major target of glycosylation. Here, we challenge this view with evidence that mammalian cells use RNA as a third scaffold for glycosylation in the secretory pathway. Using a battery of chemical and biochemical approaches, we find that a select group of small noncoding RNAs including Y RNAs are modified with complex, sialylated N-glycans (glycoRNAs). These glycoRNA are present in multiple cell types and mammalian species, both in cultured cells andin vivo. Finally, we find that RNA glycosylation depends on the canonical N-glycan biosynthetic machinery within the ER/Golgi luminal spaces. Collectively, these findings suggest the existence of a ubiquitous interface of RNA biology and glycobiology suggesting an expanded role for glycosylation beyond canonical lipid and protein scaffolds.
Chemerin increases T-cell mediated cytotoxicity of human tumors via modulation of a novel CMKLR1/PTEN/PD-L1 axis
Authors: Rennier Keith , Krug Ethan , Virdi Gurpal , Shin Woo Jae , Pachynski Russell 
Published: September 2019

AbstractChemerin (RARRES2) is an endogenous leukocyte chemoattractant known to recruit innate immune cells through its chemotactic receptor, CMKLR1. RARRES2 is often downregulated in prostate cancer and across multiple tumor types compared to normal tissue. Additionally, a methylome-wide analysis identified RARRES2 as one of the most hypermethylated genes in sarcoma. Recent studies have shown that augmenting chemerin in the tumor microenvironment significantly suppresses tumor growth, at least in part by recruitment of immune effector cells. However, as tumor cells have been shown to express functional chemokine receptors that can impact their phenotype, we hypothesized that chemerin might have additional, tumor-intrinsic effects. Here, we show for the first time that human cancer cells exposed to exogenous chemerin significantly upregulate PTEN expression and activity. Additionally, chemerin-induced PTEN expression correlated with a concomitant reduction in PD-L1 mRNA and protein expression. Chemerin treatment of tumor cells led to significantly reduced tumor cell migration/invasion, as well as significantly increased cytotoxicity by T cells. siRNA knockdown of tumor expressed CMKLR1 abrogated chemerin-induced modulation of PTEN and PD-L1 expression and activity, supporting the presence of a CMKLR1/PTEN/PD-L1 signaling cascade. We then compared chemerin treatment to PD-L1 inhibition by siRNA knockdown or the antagonistic antibody atezolizumab in T cell cytotoxicity assays and surprisingly found chemerin treatment was as effective as both PD-L1 knockdown and atezolizumab treatment in mediating tumor lysis. Collectively, our data show a novel link between chemerin, PTEN and PD-L1 in human tumor lines, with functional consequences that may have a role in improving T cell-mediated immunotherapies.
White matter microstructure in attention-deficit/hyperactivity disorder: a systematic tractography study in 654 individuals
Authors: Damatac Christienne G. , Chauvin Roselyne J. M. , Zwiers Marcel P. , van Rooij Daan , Akkermans Sophie E. A. , Naaijen Jilly , Hoekstra Pieter J. , Hartman Catharina A. , Oosterlaan Jaap , Franke Barbara , Buitelaar Jan K. , Beckmann Christian F. , Sprooten Emma 
Published: September 2019

AbstractBackgroundAttention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity (HI). ADHD has been related to differences in white matter (WM) microstructure. However, much remains unclear regarding the nature of these WM differences, and which clinical aspects of ADHD they reflect. We systematically investigated if FA is associated with current and/or lifetime categorical diagnosis, impairment in daily life, and continuous ADHD symptom measures.MethodsDiffusion-weighted imaging (DWI) data were obtained from 654 participants (322 unaffected, 258 affected, 74 subthreshold; 7-29 years of age). We applied automated global probabilistic tractography on 18 major WM pathways. Linear mixed effects regression models were used to examine associations of clinical measures with overall brain and tract-specific fractional anisotropy (FA).ResultsThere were significant interactions of tract with all ADHD variables on FA. There were no significant associations of FA with current or lifetime diagnosis, nor with impairment. Lower FA in the right cingulum’s angular bundle (rCAB) was associated with higher hyperactivity/impulsivity symptom severity (PFWE=0.045). There were no significant effects for other tracts.ConclusionsThis is the first time global probabilistic tractography has been applied to an ADHD dataset of this size. We found no evidence for altered FA in association with ADHD diagnosis. Our findings indicate that associations of FA with ADHD are not uniformly distributed across WM tracts. Continuous symptom measures of ADHD may be more sensitive to FA than diagnostic categories. The rCAB in particular may play a role in symptoms of hyperactivity and impulsivity.
Flexible binding of m6A reader protein YTHDC1 to its preferred RNA motif
Authors: Li Yaozong , Bedi Rajiv Kumar , Wiedmer Lars , Huang Danzhi , Śledź Paweł , Caflisch Amedeo 
Published: September 2019

AbstractN6-methyladenosine (m6A) is the most prevalent chemical modification in human mRNAs. Its recognition by reader proteins enables many cellular functions, including splicing and translation of mRNAs. However, the binding mechanisms of m6A-containing RNAs to their readers are still elusive due to the unclear roles of m6A-flanking ribonucleotides. Here, we use a model system, YTHDC1 with its RNA motif 5’-G−2G−1(m6A)C+1U+2-3’, to investigate the binding mechanisms by atomistic simulations, X-ray crystallography, and isothermal titration calorimetry. The experimental data and simulation results show that m6A is captured by an aromatic cage of YTHDC1 and the 3’ terminus nucleotides are stabilized by cation-π-π interactions, while the 5’ terminus remains flexible. Moreover, simulations of unbound RNA motifs reveal that the methyl group of m6A and the 5’ terminus shift the conformational preferences of the oligoribonucleotides to the bound-like conformation, thereby facilitating the association process. The proposed binding mechanisms may help in the discovery of chemical probes against m6A reader proteins.
Promoting creativity and innovation: expected and unexpected consequences
Authors: Nguyen Thi Hong , Le Angelina Nhat-Hanh 
Published: September 2019

Purpose
The paper aims to explore the role of climate for creativity and innovation as the situational variable to lead to both expected and unexpected consequences (e.g. performance and unethical behavior), by discovering the relationships among task characteristics (e.g. difficulty, clarity and performance pressure), individual psychological aspects (e.g. mindfulness and self-justification) and work environmental conditions (e.g. peer behavior and climate for creativity and innovation). In this study, task characteristics are proposed to positively associate with unethical behavior via mindfulness. Moreover, climate for creativity and innovation is proposed to moderate the relationship between self-justification and unethical behavior. Finally, unethical behavior is predicted to positively influence on performance.

Design/methodology/approach
Data were collected from the sample of salespeople, who are working for variety of companies in Vietnam. Partial least squares structural equation modeling (PLS-SEM) and SmartPLS 3 are implemented to test the path model.

Findings
Emphasizing both bright and dark sides of promoting creativity and innovation, the study highlights the role of climate for creativity and innovation in strengthening the positive relationship between self-justification and unethical behavior. In turn, unethical behavior positively influences performance. Further, the findings indicate that mindfulness contributes in explaining unconscious unethical behavior.

Originality/value
Exploring the relationships among climate for creativity and innovation, unethical behavior and performance, this paper contributes for deeper understanding of variety aspects of innovation. Demands for an intelligent management in modern workplaces are suggested.
Traditional agro-ecosystems in Southern Philippines
Authors: Zapico Florence , Hernandez Jose , Borromeo Teresita , McNally Kenneth , Dizon Josefina , Fernando Edwino 
Published: September 2019

Purpose
Sarangani, a province in Southern Philippines, is inhabited predominantly by tribal groups who depend on traditional rice farming for subsistence and livelihood. The purpose of this study is to identify current pressures to these upland communities and the interventions instituted to address them or mitigate their effects.

Design/methodology/approach
This is an exploratory and cross-sectional research using the emic approach. Rapid rural appraisal techniques (i.e. focus group discussion, key informant interviews, community immersion and field observation) were concurrently undertaken in 15 farming villages in the Sarangani uplands.

Findings
Results revealed that many upland families inhabited disaster-prone areas under conditions of hardship and abject poverty. Prevalent problems in these areas have largely arisen from the encroachment of modern agriculture, environmental degradation and changes in the socio-political and economic spheres. Consequently, food insecurity, cultural and genetic erosion and biodiversity losses have resulted in lowered Sarangani agro-ecosystem resilience. While policies and programs had been instituted to address these problems, positive results still remain to be realized.

Social implications
Weak social networks in the Sarangani upland communities are attributable to their isolation and the disruptive influences of modernization. Agricultural modernization, in particular, caused the disintegration of community social structures and undermined overall well-being of the farmers. Sustainable strategies which harmonize modern and traditional systems of food production and environmental management are warranted to attain food security, environmental preservation and bio-cultural preservation.

Originality/value
This study contributes to the present body of knowledge about threats to vulnerable agro-ecosystems inhabited mainly by indigenous tribes. And while only 15 farming villages were covered by the study, these results can serve as a microcosm of what is happening in traditional agro-ecosystems worldwide. The study is also expected to provide inputs to policymakers, which they can use in crafting policies to address problems in the Sarangani uplands.