bluuebunny/crossref_metadata_2025 huggingface dataset:
Delineation of the SUMO-Modified Proteome Reveals Regulatory Functions Throughout Meiosis
Authors: Bhagwat Nikhil R , Owens Shannon , Ito Masaru , Boinapalli Jay , Poa Philip , Ditzel Alexander , Kopparapu Srujan , Mahalawat Meghan , Davies Owen R , Collins Sean R , Johnson Jeffrey , Krogan Nevan J , Hunter Neil
Published: November 2019

Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets have been identified. Here we delineate a multidimensional SUMO-modified meiotic proteome in budding yeast, identifying 2747 conjugation sites in 775 targets, and defining their relative levels and dynamics. Modified sites cluster in disordered regions and only a minority match consensus motifs. Target identities and modification dynamics imply that SUMOylation regulates all levels of chromosome organization and each step of homologous recombination. Execution-point analysis confirms these inferences, revealing functions for SUMO in S-phase, the initiation of recombination, chromosome synapsis and crossing over. K15-linked SUMO chains become prominent as chromosomes synapse and recombine, consistent with roles in these processes. SUMO also modifies ubiquitin, forming hybrid oligomers with potential to modulate ubiquitin signaling. We conclude that SUMO plays diverse and unanticipated roles in regulating meiotic chromosome metabolism.
Protein thermal stability does not correlate with cellular half-life: Global observations and a case study of tripeptidyl-peptidase 1
Authors: Collier Aaron M. , Nemtsova Yuliya , Kuber Narendra , Banach-Petrosky Whitney , Modak Anurag , Sleat David E. , Nanda Vikas , Lobel Peter
Published: November 2019

Late-infantile neuronal ceroid lipofuscinosis (LINCL) is a neurodegenerative lysosomal storage disorder caused by mutations in the gene encoding the protease tripeptidyl-peptidase 1 (TPP1). Progression of LINCL can be slowed or halted by enzyme replacement therapy, where recombinant human TPP1 is administered to patients. In this study, we utilized protein engineering techniques to increase the stability of recombinant TPP1 with the rationale that this may lengthen its lysosomal half-life, potentially increasing the potency of the therapeutic protein. Utilizing multiple structure-based methods that have been shown to increase the stability of other proteins, we have generated and evaluated over 70 TPP1 variants. The most effective mutation, R465G, increased the melting temperature of TPP1 from 55.6°C to 64.4°C and increased its enzymatic half-life at 60°C from 5.4 min to 21.9 min. However, the intracellular half-life of R465G and all other variants tested in cultured LINCL-patient derived lymphoblasts was similar to that of WT TPP1. These results provide structure/function insights into TPP1 and indicate that improvingin vitrothermal stability alone is insufficient to generate TPP1 variants with improved physiological stability. This conclusion is supported by a proteome-wide analysis that indicates that lysosomal proteins have higher melting temperatures but also higher turnover rates than proteins of other organelles. These results have implications for similar efforts where protein engineering approaches, which are frequently evaluatedin vitro, may be considered for improving the physiological properties of proteins, particularly those that function in the lysosomal environment.
TorsinB overexpression prevents abnormal twisting in DYT1 dystonia mouse models
Authors: Li Jay , Liang Chun-Chi , Pappas Samuel S. , Dauer William T.
Published: November 2019

Genetic redundancy can be exploited to identify therapeutic targets for inherited disorders. An example is DYT1 dystonia, a neurodevelopmental movement disorder caused by a loss-of-function (LOF) mutation in theTOR1Agene encoding torsinA. Prior work demonstrates that torsinA and its paralog torsinB have conserved functions at the nuclear envelope. This work established that low neuronal levels of torsinB dictate the neuronal selective phenotype of nuclear membrane budding. Here, we examined whether torsinB expression levels impact the onset or severity of abnormal movements, or neuropathological features in DYT1 mouse models. We demonstrate that torsinB levels bidirectionally regulate these phenotypes. Reducing torsinB levels causes a dosedependent worsening whereas torsinB overexpression rescues torsinA LOF-mediated abnormal movements and neurodegeneration. These findings identify torsinB as a potent modifier of torsinA LOF phenotypes and suggest that augmentation of torsinB expression level may retard or prevent symptom development in DYT1 dystonia.
A Graph Auto-Encoder for Haplotype Assembly and Viral Quasispecies Reconstruction
Authors: Ke Ziqi , Vikalo Haris
Published: November 2019

Reconstructing components of a genomic mixture from data obtained by means of DNA sequencing is a challenging problem encountered in a variety of applications including single individual haplotyping and studies of viral communities. High-throughput DNA sequencing platforms oversample mixture components to provide massive amounts of reads whose relative positions can be determined by mapping the reads to a known reference genome; assembly of the components, however, requires discovery of the reads’ origin – an NP-hard problem that the existing methods struggle to solve with the required level of accuracy. In this paper, we present a learning framework based on a graph auto-encoder designed to exploit structural properties of sequencing data. The algorithm is a neural network which essentially trains to ignore sequencing errors and infers the posterior probabilities of the origin of sequencing reads. Mixture components are then reconstructed by finding consensus of the reads determined to originate from the same genomic component. Results on realistic synthetic as well as experimental data demonstrate that the proposed framework reliably assembles haplotypes and reconstructs viral communities, often significantly outperforming state-of-the-art techniques. Source codes and datasets are publicly available athttps://github.com/WuLoli/GAEseq.
Decoding the multimorbidities among psychiatric disorders and cognitive functioning
Authors: Golovina E. , Vickers M.H. , Erb C.D. , O’Sullivan J.M.
Published: November 2019

The regulatory contribution that single-nucleotide polymorphisms (SNPs) associated with psychiatric and cognitive phenotypes make to multimorbidity is unknown. Here, we integrate 3D genome organization and expression quantitative trait (eQTL) analyses to identify the genes and biological pathways that are functionally impacted by 2,893 GWAS SNPs associated with cognitive functioning and five psychiatric disorders (i.e. attention deficit hyperactivity disorder (ADHD), anxiety, bipolar disorder (BD), unipolar depression (UD) and schizophrenia (SCZ)). The analysis revealed 33 genes and 62 pathways that were commonly affected by the gene regulatory interactions associated with all six phenotypes despite there being no common SNPs and eQTLs. 38 ADHD-, 78 anxiety-, 81 BD-, 169 UD-, 225 SCZ- and 185 cognition-associated genes represent known drug targets. Four genes were affected by eQTLs from all six phenotypes. Collectively, our results represent the foundation for a shift from a gene-targeted towards a pathway-based approach to the treatment of multimorbid conditions.
A novel pathway linking plasma membrane and chloroplasts is co-opted by pathogens to suppress salicylic acid-dependent defences
Authors: Medina-Puche Laura , Tan Huang , Dogra Vivek , Wu Mengshi , Rosas-Diaz Tabata , Wang Liping , Ding Xue , Zhang Dan , Fu Xing , Kim Chanhong , Lozano-Duran Rosa
Published: November 2019

Chloroplasts are crucial players in the activation of defensive hormonal responses during plant-pathogen interactions. Here, we show that a plant virus-encoded protein re-localizes from the plasma membrane to chloroplasts upon triggering plant defence, interfering with the chloroplast-dependent activation of anti-viral salicylic acid (SA) biosynthesis. Strikingly, we have found that plant pathogens from different kingdoms seem to have convergently evolved to target chloroplasts and impair SA-dependent defences following an association with membranes, which is based on the co-existence of two subcellular targeting signals, an N-myristoylation site and a chloroplast transit peptide. This pattern is also present in plant proteins, at least one of which conversely activates SA defences from the chloroplast. Taken together, our results suggest that a pathway linking plasma membrane to chloroplasts and activating defence exists in plants, and that such pathway has been co-opted by plant pathogens during host-pathogen co-evolution to promote virulence through suppression of SA responses.
Dispersal patterns of Trypanosoma cruzi in Arequipa, Peru
Authors: Berry Alexander S.F. , Salazar-Sánchez Renzo , Castillo-Neyra Ricardo , Borrini-Mayorí Katty , Arevalo-Nieto Claudia , Chipana-Ramos Claudia , Vargas-Maquera Melina , Ancca-Juarez Jenny , Náquira-Velarde César , Levy Michael Z. , Brisson Dustin
Published: November 2019

Anthropogenic environmental alterations such as urbanization can threaten native populations as well as create novel environments that allow human pests and pathogens to thrive. As the number and size of urban environments increase globally, it is more important than ever to understand the dispersal dynamics of hosts, vectors and pathogens of zoonotic disease systems. For example, a protozoan parasite and the causative agent of Chagas disease in humans, Trypanosoma cruzi, recently colonized and spread through the city of Arequipa, Peru. We used population genomic and phylogenomic tools to analyze whole genomes of 123 T. cruzi isolates collected throughout Arequipa to determine patterns of T. cruzi dispersal. The data show significant population genetic structure within city blocks-parasites in the same block tend to be very closely related - but no population structure among blocks within districts - parasites in neighboring blocks are no more closely related to one another than to parasites in distant districts. These data suggest that T. cruzi dispersal within a block occurs regularly and that occasional long-range dispersal events allow the establishment of new T. cruzi populations in distant blocks. Movement of domestic animals may be the primary mechanism of inter-block and inter-district T. cruzi dispersal.

Author Summary

Urbanization creates environments that are ideal for some human pests and pathogens. As the number and size of urban environments increases globally, it is becoming vital to understand how human disease-causing pathogens, their vectors, and their non-human hosts disperse through urban landscapes. Here we study a population of Trypanosoma cruzi – the protozoan parasite and causative agent of Chagas disease in humans – that recently colonized the city of Arequipa, Peru. We use population genomic and phylogenomic tools to understand how this parasite population dispersed through the city to achieve its current distribution and abundance. We show that T. cruzi collected from the same city block tend to be very closely related, while those from neighboring blocks are often as distantly related as those from blocks in distant districts. The data suggest that vectors facilitate frequent within-block dispersal of the parasite, while domestic animal movement may facilitate the relatively infrequent inter-block and interdistrict dispersal.
An anti-adhesive surface coating reduces adhesion during contact with cribellar threads in Pholcus phalangioides (Araneae, Pholcidae) but not in the web-owning spider Uloborus plumipes(Araneae, Uloboridae)
Authors: Frutiger Miriam , Kropf Christian
Published: November 2019

Cribellar threads are powerful tools for web spiders to catch and retain prey. Spiders encountering such threads, like cribellar web spiders or araneophagic spiders invading cribellar webs, should have a protective mechanism against the adhesion of these threads. We tested for an anti-adhesive surface coating in the web invader Pholcus phalangioides and the cribellate orb weaver Uloborus plumipes. We calculated an index of adhesion for differently treated legs of the two species in a cribellar U. plumipes capture thread, i.e. untreated legs, water-washed legs, and legs washed with the organic solvent n-hexane. The results show that legs of P. phalangioides stick significantly stronger when washed with n-hexane. Our interpretation is that P. phalangioides has an organic surface coating lowering the adhesive force of the cribellar thread. No such mechanism was found in U. plumipes.
An indigenousSaccharomyces uvarumpopulation with high genetic diversity dominates uninoculated Chardonnay fermentations at a Canadian winery
Authors: McCarthy Garrett C. , Morgan Sydney C. , Martiniuk Jonathan T. , Newman Brianne L. , Measday Vivien , Durall Daniel M.
Published: November 2019

Saccharomyces cerevisiaeis the primary yeast species responsible for most fermentations in winemaking. However, other yeasts, includingSaccharomyces uvarum, have occasionally been found conducting commercial fermentations around the world.S. uvarumis typically associated with white wine fermentations in cool-climate wine regions, and has been identified as the dominant yeast in fermentations from France, Hungary, northern Italy, and, recently, Canada. However, little is known about how the origin and genetic diversity of the CanadianS. uvarumpopulation relates to strains from other parts of the world. In this study, a highly diverseS. uvarumpopulation was found dominating uninoculated commercial fermentations of Chardonnay grapes sourced from two different vineyards. Most of the strains identified were found to be genetically distinct fromS. uvarumstrains isolated around the world. Of the 106 strains ofS. uvarumidentified in this study, four played a dominant role in the fermentations, with some strains predominating in the fermentations from one vineyard over the other. Furthermore, two of the dominant strains were previously identified as dominant strains in uninoculated Chardonnay fermentations at the same winery two years earlier, providing evidence for a winery-resident population of indigenousS. uvarum. This research provides a valuable insight into the diversity and persistence of non-commercialS. uvarumstrains in North America, and provides a stepping stone for future work into the enological potential of an alternativeSaccharomycesyeast species.
Subjective value then confidence in human ventromedial prefrontal cortex
Authors: Shapiro Allison D. , Grafton Scott T.
Published: November 2019

Two fundamental goals of decision making are to select actions that maximize rewards while minimizing costs and to have strong confidence in the accuracy of a judgment. Neural signatures of these two forms of value: the subjective value (SV) of choice alternatives and the value of the judgment (confidence), have both been observed in ventromedial prefrontal cortex (vmPFC). However, the relationship between these dual value signals and their relative time courses are unknown. We recorded fMRI while 28 men and women performed a two-phase Ap-Av task with mixed-outcomes of monetary rewards paired with painful shock stimuli. Neural responses were measured during offer valuation (offer phase) and choice valuation (commit phase) and analyzed with respect to observed decision outcomes, model-estimated SV and confidence. During the offer phase, vmPFC tracked SV and decision outcomes, but it not confidence. During the commit phase, vmPFC tracked confidence, computed as the quadratic extension of SV, but it bore no significant relationship with the offer valuation itself, nor the decision. In fact, vmPFC responses from the commit phase were selective for confidence even for rejected offers, wherein confidence and SV were inversely related. Conversely, activation of the cognitive control network, including within lateral prefrontal cortex (lPFC) and dorsal anterior cingulate cortex (dACC) was associated with ambivalence, during both the offer and commit phases. Taken together, our results reveal complementary representations in vmPFC during value-based decision making that temporally dissociate such that offer valuation (SV) emerges before decision valuation (confidence).
SOX9 is required for kidney fibrosis and regulates NAV3 to control renal myofibroblast function in mice and humans
Authors: Raza Sayyid , Jokl Elliot , Pritchett James , Martin Katherine , Su Kim , Simpson Kara , Mullan Aoibheann F , Athwal Varinder , Doherty Daniel T , Zeef Leo , Henderson Neil C , Kalra Philip A , Hanley Neil A , Hanley Karen Piper
Published: November 2019

Renal fibrosis is a common endpoint for many chronic kidney diseases. Extracellular matrix (ECM) from myofibroblasts causes progressive scarring and organ failure. The mechanisms underlying fibrogenesis and how it is sustained are incompletely understood. Here, we show that the transcription factor, Sex determining region Y-box 9 (SOX9), is required for kidney fibrosis. From genome-wide analysis we identify Neuron navigator 3 (NAV3) downstream of SOX9. NAV3 was upregulated in kidney disease in patients and following renal injury in mice colocalised with SOX9. By establishing an in vitro model of renal pericyte transition to myofibroblast we demonstrated that NAV3 is required for multiple aspects of fibrogenesis including actin polymerization linked to cell migration and sustaining SOX9 and active YAP1 levels. In summary, our work discovers novel SOX9-NAV3-YAP1/SOX9 circuitry as a new mechanism to explain the progression of kidney fibrosis and points to NAV3 as a novel target for pharmacological intervention.
A lifespan program of mouse synaptome architecture
Authors: Cizeron Mélissa , Qiu Zhen , Koniaris Babis , Gokhale Ragini , Komiyama Noboru H. , Fransén Erik , Grant Seth G.N.
Published: November 2019

How synapses change molecularly during the lifespan and across all brain circuits is unknown. We analyzed the protein composition of billions of individual synapses from birth to old age on a brain-wide scale in the mouse, revealing a program of changes in the lifespan synaptome architecture spanning individual dendrites to the systems level. Three major phases were uncovered, corresponding to human childhood, adulthood and old age. An arching trajectory of synaptome architecture drives the differentiation and specialization of brain regions to a peak in young adults before dedifferentiation returns the brain to a juvenile state. This trajectory underscores changing network organization and hippocampal physiology that may account for lifespan transitions in intellectual ability and memory, and the onset of behavioral disorders.

One sentence summary

The synaptome architecture of the mouse brain undergoes continuous changes that organize brain circuitry across the lifespan.
PHGDH supports liver ceramide synthesis and sustains lipid homeostasis
Authors: Kang Yun Pyo , Falzone Aimee , Liu Min , Saller James J. , Karreth Florian A. , DeNicola Gina M.
Published: November 2019

Background

D-3-phosphoglycerate dehydrogenase (PHGDH), which encodes the first enzyme in serine biosynthesis, is overexpressed in human cancers and has been proposed as a drug target. However, whether PHGDH is critical for the proliferation or homeostasis of tissues following the postnatal period is unknown.

Methods

To study PHGDH inhibition in adult animals, we developed a knock-in mouse model harboring a PHGDH shRNA under the control of a doxycycline-inducible promoter. With this model, PHGDH depletion can be globally induced in adult animals, while sparing the brain due to poor doxycycline delivery.

Results

We found that PHGDH depletion is well tolerated and no overt phenotypes were observed in multiple highly proliferative cell compartments. Further, despite detectable knockdown, liver and pancreatic function were normal. Interestingly, diminished PHGDH expression in the liver reduced serine and ceramide levels without increasing the levels of deoxysphingolipids. Further, liver triacylglycerol profiles were altered, with an accumulation of longer chain, polyunsaturated tails upon PHGDH knockdown.

Conclusions

These results suggest that dietary serine is adequate to support the function of healthy, adult murine tissues, but PHGDH-derived serine supports liver ceramide synthesis and sustains general lipid homeostasis.
Tool recommender system in Galaxy using deep learning
Authors: Kumar Anup , Grüning Björn , Backofen Rolf
Published: November 2019

Galaxy is a web-based and open-source scientific data-processing platform. Researchers compose pipelines in Galaxy to analyse scientific data. These pipelines, also known as workflows, can be complex and difficult to create from thousands of tools, especially for researchers new to Galaxy. To make creating workflows easier, faster and less error-prone, a predictive system is developed to recommend tools facilitating further analysis. A model is created to recommend tools by analysing workflows, composed by researchers on the European Galaxy server, using a deep learning approach. The higher-order dependencies in workflows, represented as directed acyclic graphs, are learned by training a gated recurrent units (GRU) neural network, a variant of a recurrent neural network (RNN). The weights of tools used in the neural network training are derived from their usage frequencies over a period of time. The hyper-parameters of the neural network are optimised using Bayesian optimisation. An accuracy of 97% in predicting tools is achieved by the model for precision@1, precision@2 and precision@3 metrics. It is accessed by a Galaxy API to recommend tools in real-time. Multiple user interface (UI) integrations on the server communicate with this API to apprise researchers of these recommended tools interactively.

Contact

kumara@informatik.uni-freiburg.de

gruening@informatik.uni-freiburg.de

backofen@informatik.uni-freiburg.de
Purification and molecular characterization of phospholipase, antigen 5 and hyaluronidases from the venom of the Asian hornet (Vespa velutina)
Authors: Monsalve Rafael I. , Gutiérrez Ruth , Hoof Ilka , Lombardero Manuel
Published: November 2019

The aim of this study was to purify potential allergenic components of Vespa velutina venom, the yellow legged Asian Hornet, and perform a preliminary characterization of the purified proteins. Starting from the whole venom of V.velutina, several chromatographic steps allowed to purify the phospholipase (named Vesp v 1), as well as the antigen 5 (Vesp v 5, the only allergenic component described as such so far). The two hyaluronidase isoforms found (Vesp v 2A and Vesp v 2B) cannot be separated from each other, but they are partially purified and characterized. Purity of the isolated proteins in shown by SDSPAGE, as well as by the results of the N-terminal sequencing. This characterization and nLC-MS/MS data provide most of the sequence for Vesp v 1 and Vesp v 5 (72 and 84% coverage, respectively), confirming that the whole sequences of the isolated natural components match with the data available in public transcriptomic databases. It is of particular interest that Vesp v 1 is a glycosylated phospholipase, a fact that had only described so far for the corresponding allergen components of Dolichovespula maculata and Solenopsis invicta.

The availability of the complete sequences of Vespa velutina components permits comparison with homologous sequences from other Hymenoptera. These data demonstrate the higher similarity among the species of the genera Vespa and Vespula, in comparison to Polistes species, as it is especially observed with the hyaluronidases isoforms: the isoform Vesp v 2A only exists in the former genera, and not in Polistes; in addition, the most abundant isoform (Vesp v 2B) exhibits 93% sequence identity with the Ves v 2 isoform of Vespula vulgaris.

Finally, the isolated components might be useful for improving the diagnosis of patients that could be allergic to stings of this invasive Asian hornet, as it has been the case of an improved diagnosis and treatment of other Hymenoptera-sensitized patients.

Data Availability Statement

Proteomic study data are deposited and made available publicly when data are published with the ProteomeExchange identifier PXD015381 in the Mass spectrometry Interactive Virtual Environment (MassIVE).

Allergen nomenclature for Vesp v 5 (and also for any future demonstrated allergen from Vespa velutina) has been approved by the WHO/IUIS Committee (www.allergen.org); when this manuscript is accepted, the WHO/IUIS Committee will be informed so that the complete sequences included in this manuscript are also included in their database (with links to the UNIPROT database, who will also be informed that the data can be made public).
Functional hyperemia drives fluid exchange in the paravascular space
Authors: Kedarasetti Ravi Teja , Turner Kevin L. , Echagarruga Christina , Gluckman Bruce G. , Drew Patrick J. , Costanzo Francesco
Published: November 2019

Maintaining the ionic and chemical composition of the extracellular spaces in the brain is extremely important for its health and function. However, the brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that the fluid movement through the paravascular space (PVS) surrounding penetrating arteries can help remove metabolites from the brain. The dynamics of fluid movement in the PVS and its interaction with arterial dilation and brain mechanics are not well understood. Here, we performed simulations to understand how arterial pulsations and dilations interact with brain deformability to drive fluid flow in the PVS. In simulations with compliant brain tissue, arterial pulsations did not drive appreciable flows in the PVS. In contrast, when the artery dilated with dynamics like those seen during functional hyperemia, there was a marked movement of fluid through the PVS. Our simulations suggest that in addition to its other purposes, functional hyperemia may serve to increase fluid exchange between the PVS and the subarachnoid space, improving the clearance of metabolic waste. We measured displacement of the blood vessels and the brain tissue simultaneously in awake, head-fixed mice using two-photon microscopy. Our measurements show that brain tissue can deform in response to fluid movement in the PVS, as predicted by simulations. The results from our simulations and experiments show that the deformability of the soft brain tissue needs to be accounted for when studying fluid flow and metabolite transport in the brain.
Correlations in population dynamics in multi-component networks
Authors: Saraf Sonica , Young Lai-Sang
Published: November 2019

This is a theoretical study of correlations in spiking activity between neuronal populations. We focus on the spike firing of entire local populations without regard to the identities of the neurons that fire the spikes, and show that such a population-level metric is more robust than correlations between pairs of neurons. Between any source and target populations, there is an intrinsic response time characterized by the phase-shift that maximizes the correlation between their spiking. We find that the alignment of gamma-band rhythms contributes significantly to the positive correlations between populations. Hence, the correlation metric sheds light on the transference of gamma rhythms between populations; the effectiveness of such transference has been hypothesized to be connected to communication between brain regions. We investigate the dependence of correlations on connectivity and degree of synchrony, and consider multi-component network motifs with configurations known to occur in real cortex, studying the correlations between components that are directly or indirectly connected, by single or multiple pathways, with or without feedback. Mechanistic explanations are offered for many of the phenomena observed.
Cell-type specific asynchronous modulation of PKA by dopamine during reward based learning
Authors: Lee Suk Joon , Lodder Bart , Chen Yao , Patriarchi Tommaso , Tian Lin , Sabatini Bernardo L.
Published: November 2019

Canonical reinforcement learning models postulate that dopamine neurons encode reward prediction error (RPE) and provide a teaching signal to striatal spiny projection neurons (SPNs) in the form of dopamine (DA) release. DA is thought to guide learning via dynamic modulation of protein kinase A (PKA) in SPNs. However, this fundamental assumption remains untested in behaving animals. Here we utilized multi-channel fiber photometry and fluorescence lifetime photometry (FLiP) to monitor the activity of DA neurons, extracellular DA levels, and net PKA activity in SPNs in the nucleus accumbens during learning. We found dynamic encoding of RPE in the activity of DA neurons, which is both necessary and sufficient to explain striatal DA levels and SPN PKA activity. The modulation of PKA in SPNs that express type-1 (D1R-SPNs) and type-2 (D2R-SPNs) DA receptors was dichotomous such that in each cell class it is selectively sensitive to increases and decreases in DA, respectively, and occur at and support different phases of learning. Thus, PKA-dependent pathways in D1R- and D2R-SPNs are asynchronously engaged by RPE-encoding DA signals to promote different aspects of reinforcement learning: the former responsible for the initial association between action and outcome and the latter responsible for refining the learned association.
Principles of tactile search over the body
Authors: Halfen Elizabeth J. , Magnotti John F. , Rahman Md. Shoaibur , Yau Jeffrey M.
Published: November 2019

Although we experience complex patterns over our entire body, how we selectively perceive multi-site touch over our bodies remains poorly understood. Here, we characterized tactile search behavior over the body using a tactile analog of the classic visual search task. Participants judged whether a target stimulus (e.g., 10-Hz vibration) was present or absent on the upper or lower limbs. When present, the target stimulus could occur alone or with distractor stimuli (e.g., 30-Hz vibrations) on other body locations. We varied the number and spatial configurations of the distractors as well as the target and distractor frequencies and measured the impact of these factors on search response times. First, we found that response times were faster on target-present trials compared to target-absent trials. Second, response times increased with the number of stimulated sites, suggesting a serial search process. Third, search performance differed depending on stimulus frequencies. This frequency-dependent behavior may be related to perceptual grouping effects based on timing cues. We constructed models to explore how the locations of the tactile cues influenced search behavior. Our modeling results reveal that, in isolation, cues on the index fingers make relatively greater contributions to search performance compared to stimulation experienced on other body sites. Additionally, co-stimulation of sites within the same limb or simply on the same body side preferentially influence search behavior. Our collective findings identify some principles of attentional search that are common to vision and touch, but others that highlight key differences that may be unique to body-based spatial perception.

New & Noteworthy

Little is known about how we selectively experience multi-site touch over the body. Using a tactile analog of the classic visual search paradigm, we show that tactile search behavior for flutter cues is generally consistent with a serial search process. Modeling results reveal the preferential contributions of index finger stimulation and two-site interactions involving ipsilateral and within-limb patterns. Our results offer initial evidence for spatial and temporal principles underlying tactile search behavior over the body.
Predicting master transcription factors from pan-cancer expression data
Authors: Reddy Jessica , Fonseca Marcos A. S. , Corona Rosario I , Nameki Robbin , Segato Dezem Felipe , Klein Isaac A. , Chang Heidi , Chaves-Moreira Daniele , Afeyan Lena , Malta Tathiane M , Lin Xianzhi , Abbasi Forough , Font-Tello Alba , Sabedot Thais , Cejas Paloma , Rodríguez-Malavé Norma , Seo Ji-Heui , Lin De-Chen , Matulonis Ursula , Karlan Beth Y , Gayther Simon A , Gusev Alexander , Noushmehr Houtan , Long Henry , Freedman Matthew L. , Drapkin Ronny , Abraham Brian J , Young Richard A. , Lawrenson Kate
Published: November 2019

The function of critical developmental regulators can be subverted by cancer cells to control expression of oncogenic transcriptional programs. These "master transcription factors" (MTFs) are often essential for cancer cell survival and represent vulnerabilities that can be exploited therapeutically. The current approaches to identify candidate MTFs examine super-enhancer associated transcription factor-encoding genes with high connectivity in network models. This relies on chromatin immunoprecipitation-sequencing (ChIP-seq) data, which is technically challenging to obtain from primary tumors, and is currently unavailable for many cancer types and clinically relevant subtypes. In contrast, gene expression data are more widely available, especially for rare tumors and subtypes where MTFs have yet to be discovered. We have developed a predictive algorithm called CaCTS (Cancer Core Transcription factor Specificity) to identify candidate MTFs using pan-cancer RNA-sequencing data from The Cancer Genome Atlas. The algorithm identified 273 candidate MTFs across 34 tumor types and recovered known tumor MTFs. We also made novel predictions, including for cancer types and subtypes for which MTFs have not yet been characterized. Clustering based on MTF predictions reproduced anatomic groupings of tumors that share 1-2 lineage-specific candidates, but also dictated functional groupings, such as a squamous group that comprised five tumor subtypes sharing 3 common MTFs. PAX8, SOX17, and MECOM were candidate factors in high-grade serous ovarian cancer (HGSOC), an aggressive tumor type where the core regulatory circuit is currently uncharacterized. PAX8, SOX17, and MECOM are required for cell viability and lie proximal to super-enhancers in HGSOC cells. ChIP-seq revealed that these factors co-occupy HGSOC regulatory elements globally and co-bind at critical gene loci including MUC16 (CA-125). Addiction to these factors was confirmed in studies using THZ1 to inhibit transcription in HGSOC cells, suggesting early down-regulation of these genes may be responsible for cytotoxic effects of THZ1 on HGSOC models. Identification of MTFs across 34 tumor types and 140 subtypes, especially for those with limited understanding of transcriptional drivers paves the way to therapeutic targeting of MTFs in a broad spectrum of cancers.
In vivo nuclear RNA structurome reveals RNA-structure regulation of mRNA processing in plants
Authors: Liu Zhenshan , Liu Qi , Yang Xiaofei , Zhang Yueying , Norris Matthew , Chen Xiaoxi , Cheema Jitender , Ding Yiliang
Published: November 2019

mRNA processing is critical for gene expression. A challenge in regulating mRNA processing is how to recognize the actual mRNA processing sites, such as splice and polyadenylation sites, when the sequence content is insufficient for this purpose. Previous studies suggested that RNA structure affects mRNA processing. However, the regulatory role of RNA structure in mRNA processing remains unclear. Here, we performed in vivo selective 2’-hydroxyl acylation analysed by primer extension (SHAPE) chemical profiling on Arabidopsis nuclear RNAs and generated the in vivo nuclear RNA structure landscape. We found that nuclear mRNAs fold differently from cytosolic mRNAs. Notably, we discovered a two-nucleotide single-stranded RNA structure feature upstream of 5’ splice sites that is strongly associated with splicing and the selection of alternative 5’ splice sites. Moreover, we found the single-strandedness of branch point is also associated with 3’ splice site recognition. We also identified an RNA structure feature comprising two close-by single-stranded regions that is specifically associated with both polyadenylation and alternative polyadenylation events. Our work demonstrates an RNA structure regulatory mechanism for mRNA processing.
Computational analysis of filament polymerization dynamics in cytoskeletal networks
Authors: Caldas Paulo , Radler Philipp , Sommer Christoph , Loose Martin
Published: November 2019

The polymerization–depolymerization dynamics of cytoskeletal proteins play essential roles in the self-organization of cytoskeletal structures, in eukaryotic as well as prokaryotic cells. While advances in fluorescence microscopy and in vitro reconstitution experiments have helped to study the dynamic properties of these complex systems, methods that allow to collect and analyze large quantitative datasets of the underlying polymer dynamics are still missing. Here, we present a novel image analysis workflow to study polymerization dynamics of active filaments in a non-biased, highly automated manner. Using treadmilling filaments of the bacterial tubulin FtsZ as an example, we demonstrate that our method is able to specifically detect, track and analyze growth and shrinkage of polymers, even in dense networks of filaments. We believe that this automated method can facilitate the analysis of a large variety of dynamic cytoskeletal systems, using standard time-lapse movies obtained from experiments in vitro as well as in the living cell. Moreover, we provide scripts implementing this method as supplementary material.
Crystal structure and Hirshfeld surface analysis of a zinc xanthate complex containing the 2,2′-bipyridine ligand
Authors: Qadir Adnan M. , Kansiz Sevgi , Rosair Georgina M. , Dege Necmi , Safyanova Inna S.
Published: November 2019

In the title compound, (2,2′-bipyridine-κ2
N,N′)bis(2-methoxyethyl xanthato-κS)zinc(II), [Zn(C4H7O2S2)2(C10H8N2)], the ZnII ion is coordinated to two N atoms of the 2,2′-bipyridine ligand and two S atoms from two 2-methoxyethyl xanthate ligands. The ZnII ion lies on a crystallographic twofold rotation axis and has distorted tetrahedral coordination geometry. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, forming supramolecular chains propagating along the a-axis direction. Weak intramolecular C—H...S hydrogen bonds are also observed. The intermolecular contacts in the crystal were further analysed using Hirshfield surface analysis, which indicates that the most significant contacts are H...H (36.3%), followed by S...H/H...S (24.7%), C...H/H...C (15.1%), O...H/H...O (14.4%), N...H/H...N (4.1%) and C...C (2.9%).
Utilising low cost RGB-D cameras to track the real time progress of a manual assembly sequence
Authors: Oyekan John , Fischer Axel , Hutabarat Windo , Turner Christopher , Tiwari Ashutosh
Published: November 2019

Purpose

The purpose of this paper is to explore the role that computer vision can play within new industrial paradigms such as Industry 4.0 and in particular to support production line improvements to achieve flexible manufacturing. As Industry 4.0 requires “big data”, it is accepted that computer vision could be one of the tools for its capture and efficient analysis. RGB-D data gathered from real-time machine vision systems such as Kinect ® can be processed using computer vision techniques.

Design/methodology/approach

This research exploits RGB-D cameras such as Kinect® to investigate the feasibility of using computer vision techniques to track the progress of a manual assembly task on a production line. Several techniques to track the progress of a manual assembly task are presented. The use of CAD model files to track the manufacturing tasks is also outlined.

Findings

This research has found that RGB-D cameras can be suitable for object recognition within an industrial environment if a number of constraints are considered or different devices/techniques combined. Furthermore, through the use of a HMM inspired state-based workflow, the algorithm presented in this paper is computationally tractable.

Originality/value

Processing of data from robust and cheap real-time machine vision systems could bring increased understanding of production line features. In addition, new techniques that enable the progress tracking of manual assembly sequences may be defined through the further analysis of such visual data. The approaches explored within this paper make a contribution to the utilisation of visual information “big data” sets for more efficient and automated production.
CSR performance and annual report readability: evidence from France
Authors: Bacha Sami , Ajina Aymen
Published: November 2019

Purpose

This study aims to examine the relationship between the corporate social responsibility (CSR) performance and the readability of annual report. The shareholder theory suggests that CSR firms will provide more transparent disclosures because this reflects a socially and environmentally responsible behavior and a firm’s commitment to high ethical standards. In the same time, the agency theory offers an opposite view. It predicts that opportunistic managers use CSR as an entrenchment strategy and hide their maneuvers through complex textual financial disclosures.

Design/methodology/approach

Based on a sample of 100 listed firms on the French CACAll-shares index over the period from 2013 to 2016, the authors use a panel regression analysis and run other estimation methods (IV-2SLS) and simultaneous equation model to address the endogeneity issues. They assess the readability of annual reports using the Gunning-Fog Index and the Flesch Index derived from the computational linguistics literature.

Findings

The results show a significant positive relationship between CSR performance and the readability of annual report. Firms engaging in CSR practices are more likely to provide transparent disclosures with higher readability because this reflects a socially responsible behavior and a firm’s commitment to high ethical standards. This result supports the stakeholder theory and the corporate reputational view. The finding is also robust to alternative readability measurements and to endogeneity bias.

Practical implications

This study helps all market participants to more comprehensively evaluate the CSR performance disclosed on annual report. It encourages managers to consider CSR as a means to prevent the opacity risk through improved information quality. It also drives French authorities to better regulate the narrative disclosure of CSR firms and change the way companies design their reporting practices. Moreover, it encourages CSR rating agencies to become the dominant definition of CSR evaluation by granting more importance to the quality of disclosed information.

Originality/value

This study extends previous research on the potential impact of CSR on information quality measured by annual report readability in the French context. Unlike prior studies on the impact of CSR on information quality, that focus exclusively on earnings management and adopt qualitative approaches to assess the SCR score, the authors use simultaneously the Gunning–Fog Index and the Flesch Index to assess the information quality and extract the CSR score from the CSRHub database of companies’ social, environmental and governance performance.
Predictors of knowledge transfer between expatriates and host country nationals
Authors: Zulkifly Nurul Afiqah , Ismail Maimunah , Hamzah Siti Raba’ah
Published: November 2019

Purpose

The purpose of this paper is to investigate the influences of cultural intelligence, feedback-seeking behavior and shared vision as a mediator on bi-directional knowledge transfer involving expatriates and host country nationals (HCNs).

Design/methodology/approach

This paper integrates the signaling theory, the social capital theory and the anxiety and uncertainty theory in investigating the relationships between predictors and knowledge transfer in a bi-directional manner. The participants of the study were 125 expatriate-HCN pairs of MNCs and local organizations in the areas of Klang Valley, Malaysia.

Findings

Shared vision was found to significantly mediate the influences of cultural intelligence and feedback-seeking behavior on knowledge transfer as perceived by the respective respondents.

Originality/value

Co-existence between expatriates and HCNs leads to many organizational outcomes including knowledge transfer. This paper additionally provides theoretical and practical implications to human resource practices.
Understanding emotional customer experience and co-creation behaviours in luxury hotels
Authors: Wu Szu-Hsin , Gao Yuhui
Published: November 2019

Purpose

A holistic understanding of sources that evoke customer emotions is essential for creating a positive emotional customer experience (ECX). Despite a significant focus on the cognitive aspect of customer experience and traditional customer behaviours (e.g. loyalty and satisfaction), limited attention has been paid to ECX and co-creation behaviours. The purpose of this paper is to address this important knowledge gap by identifying different emotions and prominent sources of ECX (i.e. emotion triggers and constructors) during service interactions. By doing so, key customer co-creation behaviours are also identified, which help enhance positive customer experience.

Design/methodology/approach

A combined application of the appraisal theory and thematic analysis was used to explore ECX, its sources and co-creation behaviours as observed from 1,063 TripAdvisor customer reviews of luxury hotels in Ireland.

Findings

The results show that a single service interaction can evoke multiple emotions during the interaction process. The findings capture prominent emotions that customers experience and various important emotion triggers (physical environment, service management and offerings and human interaction) and constructors (customer expectation, accumulated service experience and culture fusion and authenticity). Three main customer co-creation behaviours (reinforcing intention, active and resourceful behaviours), which help facilitate the co-creation of positive customer emotions, are also identified.

Originality/value

The study proposes a new framework that provides unique insights into ECX to guide service improvement and innovation. A novel approach of applying the appraisal theory to a netnographic study is used to develop an ECX framework, which integrates various emotion triggers and constructors, and subsequent customer co-creation behaviours in the hotel industry.