bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible changes in fidelity of DNA polymerase δ in ancestral mammals
Authors: Katoh Kazutaka , Iwabe Naoyuki , Miyata Takashi
Published: October 2020

DNA polymerase δ (polδ) is one of the major DNA polymerases that replicate chromosomal genomes in eukaryotes. Given the essential role of this protein, its phylogenetic tree was expected to reflect the relationship between taxa, like many other essential proteins. However, the tree of the catalytic subunit of polδ showed an unexpectedly strong heterogeneity among vertebrate lineages in evolutionary rate at the amino acid level, suggesting unusual amino acid substitutions specifically in the ancestral mammalian lineage. Structural and phylogenetic analyses were used to pinpoint where and when these amino acid substitutions occurred: around the 3′-5′ exonuclease domain in later mammal ancestry, after the split between monotremes and therians. The 3′-5′ exonuclease domain of this protein is known to have an impact on the fidelity of replication. Based on these observations, we explored the possibility that the amino acid substitutions we identified in polδ affected the mutation rate of entire chromosomal genomes in this time period.
Genomic and microscopic evidence of stable high density and maternally inheritedWolbachiainfections inAnophelesmosquitoes
Authors: Walker Thomas , Quek Shannon , Jeffries Claire L. , Bandibabone Janvier , Dhokiya Vishaal , Bamou Roland , Kristan Mojca , Messenger Louisa A. , Gidley Alexandra , Hornett Emily A. , Anderson Enyia R. , Cansado-Utrilla Cintia , Hegde Shivanand , Bantuzeko Chimanuka , Stevenson Jennifer C. , Lobo Neil F. , Wagstaff Simon C. , Antonio Nkondjio Christophe , Heinz Eva , Hughes Grant L.
Published: October 2020

Wolbachia, a widespread bacterium that can reduce pathogen transmission in mosquitoes, has been detected within populations ofAnopheles (An.)malaria vectors. In theAn. gambiaecomplex, the primary vectors in Sub-Saharan Africa,Wolbachiastrains are at low density and infection frequencies in wild populations. PCR-independent evidence is required to determine whetherWolbachiastrains are true endosymbionts inAnophelesgiven most studies to date have used nested-PCR to identify strains. Here we report high-density strains found in geographically diverse populations ofAn. mouchetiandAn.demeilloni. Fluorescentin situhybridization localized a heavy infection in the ovaries ofAn. mouchetiand maternal transmission was observed. Genome sequencing of both strains obtained genome depths and coverages comparable to other known infections. Notably, homologs of cytoplasmic incompatibility factor (cif) genes were present indicating these strains possess the capacity to induce the phenotype cytoplasmic incompatibility which allowsWolbachiato spread through populations. The characteristics of these two strains suggest they are ideal candidates forWolbachiabiocontrol strategies inAnopheles.
Core Antibiotic-Induced Transcriptional Signatures Reflect Susceptibility to All Members of an Antibiotic Class
Authors: Martinsen Melanie A. , Cartagena Alexis Jaramillo , Bhattacharyya Roby P.
Published: October 2020

Current growth-based antibiotic susceptibility testing (AST) is too slow to guide early therapy. We previously developed a diagnostic approach that quantifies antibiotic-induced transcriptional signatures to distinguish susceptible from resistant isolates, providing phenotypic AST 24-36h faster than current methods. Here, we show that 10 transcripts optimized for AST of one fluoroquinolone, aminoglycoside, or beta-lactam reflect susceptibility to other members of that class. This finding will streamline development and implementation of this strategy, facilitating efficient antibiotic deployment.
CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in Huntington’s disease
Authors: Yu Dahyun , Zarate Nicole , White Angel , Coates De’jah , Tsai Wei , Nanclares Carmen , Cuccu Francesco , Yue Johnny S. , Brown Taylor G. , Mansky Rachel , Jiang Kevin , Kim Hyuck , Nichols-Meade Tessa , Larson Sarah N. , Gundry Katie , Zhang Ying , Tomas-Zapico Cristina , Lucas Jose J. , Benneyworth Michael , Öz Gülin , Cvetanovic Marija , Araque Alfonso , Gomez-Pastor Rocio
Published: October 2020

Background

Huntington’s Disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion inthe HTTgene for which no therapies are available. This mutation causes HTT protein misfolding and aggregation, preferentially affecting medium spiny neurons (MSNs) of the basal ganglia. Transcriptional perturbations in synaptic genes and neuroinflammation are key processes that precede MSN dysfunction and motor symptom onset. Understanding the interplay between these processes is crucial to develop effective therapeutic strategies to treat HD. We investigated whether protein kinase CK2α’, a kinase upregulated in MSNs in HD and previously associated with Parkinson’s disease (PD), participates in the regulation of neuroinflammation and synaptic function during HD progression.

Methods

We used the heterozygous knock-in zQ175 HD mouse model and compared that to zQ175 mice lacking one allele of CK2α’. We performed neuropathological analyses using immunohistochemistry, cytokine proteome profiling, RNA-seq analyses in the striatum, electrophysiological recordings, and behavioral analyses. We also used the murine immortalized striatal cell lines STHdhQ7and STHdhQ111and studied the expression of various synaptic genes dysregulated by CK2α’.

Results

We showed that CK2α’ haploinsufficiency in zQ175 mice ameliorated neuroinflammation, HTT aggregation, transcriptional alterations, excitatory synaptic transmission, and motor coordination deficits. RNA-seq analyses also revealed a connection between α-syn, a protein associated with PD, and the transcriptional perturbations mediated by CK2α’ in HD. We also found increased α-syn serine 129 phosphorylation (pS129-α-syn), a post-translational modification linked to α-synucleinopathy, in the nuclei of MSNs in zQ175 mice and in patients with HD. Levels of pS129-α-syn were ameliorated in zQ175 lacking one allele of CK2α’.

Conclusions

Our data demonstrated that CK2α’ contributes to transcriptional dysregulation of synaptic genes and neuroinflammation in zQ175 mice and its depletion improved several HD-like phenotypes in this mouse model. These effects were related to increased phosphorylation of S129-α-syn in the striatum of HD mice, suggesting that CK2α’ contributes to worsening HD by mediating synucleinopathy. Our study highlights a possible convergent mechanism of neurodegeneration between HD and PD and suggests targeting CK2α’ as a potential therapeutic strategy to ameliorate synaptic dysfunction in HD as well as other neurodegenerative diseases.
Evolution and adaptation ofPseudomonas aeruginosain the paranasal sinuses of people with cystic fibrosis
Authors: Armbruster Catherine R. , Marshall Christopher W. , Melvin Jeffrey A. , Zemke Anna C. , Garber Arkadiy I. , Moore John , Li Kelvin , Zamora Paula F. , Fritz Ian L. , Manko Christopher , Weaver Madison , Gaston Jordan , Morris Alison , Methé Barbara , Lee Stella E. , Cooper Vaughn S. , Bomberger Jennifer M.
Published: October 2020

People with the genetic disorder cystic fibrosis (CF) harbor lifelong respiratory infections, with morbidity and mortality frequently linked to chronic lung infections dominated by the opportunistically pathogenic bacteriumPseudomonas aeruginosa. During chronic CF lung infections, a single clone ofP. aeruginosacan persist for decades and dominate end-stage CF lung disease due to its propensity to adaptively evolve to the respiratory environment, a process termed “pathoadaptation”. Chronic rhinosinusitis (CRS), chronic inflammation and infection of the sinonasal space, is highly prevalent in CF and the sinuses may serve as the first site in the respiratory tract to become colonized by bacteria that then proceed to seed lung infections. We identified three evolutionary genetic routes by whichP. aeruginosaevolves in the sinuses of people with CF, including through the evolution of mutator lineages and proliferative insertion sequences and culminating in early genomic signatures of host-restriction. Our findings raise the question of whether a significant portion of the pathoadaptive phenotypes previously thought to have evolved in response to selective pressures in the CF lungs may have first arisen in the sinuses and underscore the link between sinonasal and lung disease in CF.

Graphical abstract and highlights

Pseudomonas aeruginosaundergoes adaptive evolution in the sinuses of people with CF

Over time, pathoadapted strains display early signatures of genome degradation consistent with recent host restriction

Mutations previously thought to occur in CF lungs may have first evolved in sinuses
Novel enzyme for dimethyl sulfide-releasing in bacteria reveals a missing route in the marine sulfur cycle
Authors: Li Chun-Yang , Wang Xiu-Juan , Chen Xiu-Lan , Sheng Qi , Zhang Shan , Wang Peng , Quareshy Mussa , Rihtman Branko , Shao Xuan , Gao Chao , Li Fuchuan , Li Shengying , Chen Yin , Zhang Yu-Zhong
Published: October 2020

Dimethylsulfoniopropionate (DMSP) is an abundant and ubiquitous organosulfur molecule and plays important roles in the global sulfur cycle. Cleavage of DMSP produces volatile dimethyl sulfide (DMS), which has impacts on the global climate. Multiple pathways for DMSP catabolism have been identified. Here we identified yet another novel pathway, the ATP DMSP lysis pathway. The key enzyme, AcoD, is an ATP-dependent DMSP lyase. AcoD belongs to the acyl-CoA synthetase superfamily, which is totally different from other DMSP lyases, showing a new evolution route. AcoD catalyses the conversion of DMSP to DMS by a two-step reaction: the ligation of DMSP with CoA to form the intermediate DMSP-CoA, which is then cleaved to DMS and acryloyl-CoA. The novel catalytic mechanism was elucidated by structural and biochemical analyses. AcoD is widely distributed in many bacterial lineages including Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria and Firmicutes, revealing this new pathway plays important roles in global DMSP/DMS cycles.
Pairwise genetic interactions modulate lipid plasma levels and cellular uptake
Authors: Zimon Magdalena , Huang Yunfeng , Trasta Anthi , Liu Jimmy Z. , Chen Chia-Yen , Halavatyi Aliaksandr , Blattmann Peter , Klaus Bernd , Whelan Christopher D. , Sexton David , John Sally , Huber Wolfgang , Tsai Ellen A. , Pepperkok Rainer , Runz Heiko
Published: October 2020

Genetic interactions (GIs), the joint impact of different genes or variants on a phenotype, are foundational to the genetic architecture of complex traits. However, identifying GIs through human genetics is challenging since it necessitates very large population sizes, while findings from model systems not always translate to humans. Here, we combined exome-sequencing and genotyping in the UK Biobank with combinatorial RNA-interference (coRNAi) screening to systematically test for pairwise GIs between 30 lipid GWAS genes. Gene-based protein-truncating variant (PTV) burden analyses from 240,970 exomes revealed additive GIs forAPOBwithPCSK9andLPL, respectively. Both, genetics and coRNAi identified additive GIs for 12 additional gene pairs. Overlapping non-additive GIs were detected only forTOMM40at theAPOElocus withSORT1andNCAN. Our study identifies distinct gene pairs that modulate both, plasma and cellular lipid levels via additive and non-additive effects and nominates drug target pairs for improved lipid-lowering combination therapies.
Rab34 GTPase mediates ciliary membrane biogenesis in the intracellular ciliogenesis pathway
Authors: Ganga Anil Kumar , Kennedy Margaret C. , Oguchi Mai E. , Gray Shawn D. , Oliver Kendall E. , Knight Tracy A. , De La Cruz Enrique M. , Homma Yuta , Fukuda Mitsunori , Breslow David K.
Published: October 2020

Primary cilia form by two pathways: an extracellular pathway in which the cilium grows out from the cell surface and an intracellular pathway in which the nascent cilium forms inside the cell. Here we identify the GTPase Rab34 as a selective mediator of intracellular ciliogenesis. We find that Rab34 is required for formation of the ciliary vesicle at the mother centriole and that Rab34 marks the ciliary sheath, a unique sub-domain of assembling intracellular cilia. Rab34 activity is modulated by divergent residues within its GTPase domain, and ciliogenesis requires GTP binding and turnover by Rab34. Because Rab34 is found on assembly intermediates that are unique to intracellular ciliogenesis, we tested its role in the extracellular pathway used by MDCK cells. Consistent with Rab34 acting specifically in the intracellular pathway, MDCK cells ciliate independently of Rab34 and paralog Rab36. Together, these findings reveal a new context-specific molecular requirement for ciliary membrane biogenesis.
Integrating protein copy numbers with interaction networks to quantify stoichiometry in mammalian endocytosis
Authors: Duan Daisy , Hanson Meretta , Holland David O. , Johnson Margaret E
Published: October 2020

Proteins that drive processes like clathrin-mediated endocytosis (CME) are expressed at various copy numbers within a cell, from hundreds (e.g. auxilin) to millions (e.g. clathrin). Between cell types with identical genomes, copy numbers further vary significantly both in absolute and relative abundance. These variations contain essential information about each protein’s function, but how significant are these variations and how can they be quantified to infer useful functional behavior? Here, we address this by quantifying the stoichiometry of proteins involved in the CME network. We find robust trends across three cell types in proteins that are sub- vs super-stoichiometric in terms of protein function, network topology (e.g. hubs), and abundance. To perform this analysis, we first constructed the interface resolved network of 82 proteins involved in CME in mammals, plus lipid and cargo binding partners, totaling over 600 specific binding interactions. Our model solves for stoichiometric balance by optimizing each copy of a protein interface to match up to its partner interfaces, keeping the optimized copies as close as possible to observed copies. We find highly expressed, structure-forming proteins such as actin and clathrin do tend to be super-stoichiometric, or in excess of their partners, but they are not the most extreme cases. We test sensitivity of network stoichiometry to protein removal and find that hub proteins tend to be less sensitive to removal of any single partner, thus acting as buffers that compensate dosage changes. As expected, tightly coupled protein pairs (e.g.CAPZA2 and CAPZB) are strongly correlated. Unexpectedly, removal of functionally similar cargo adaptor proteins produces widely variable levels of disruption to the network stoichiometry. Our results predict that knockdown of the adaptor protein DAB2 will globally impact the stoichiometry of most other cargo adaptor proteins in Hela cells, with significantly less impact in fibroblast cells. This inexpensive analysis can be applied to any protein network, synthesizing disparate sources of biological data into a relatively simple and intuitive model of binding stoichiometry that can aid in dynamical modeling and experimental design.
Sodium channel toxin-resistance mutations do not govern batrachotoxin (BTX) autoresistance in poison birds and frogs
Authors: Abderemane-Ali Fayal , Rossen Nathan D. , Kobiela Megan E. , Craig Robert A. , Garrison Catherine E. , O’Connell Lauren A. , Du Bois J. , Dumbacher John P. , Minor Daniel L.
Published: October 2020

Poisonous organisms carry small molecule toxins that alter voltage-gated sodium channel (Na✓) function. Among these, batrachotoxin (BTX) fromPitohuitoxic birds andPhyllobatespoison frogs, stands out because of its lethality and unusual effects on Navfunction. How these toxin-bearing organisms avoid autointoxication remains poorly understood. In poison frogs, a NavDIVS6 pore-forming helix N→T mutation has been proposed as the BTX resistance mechanism. Here, we show that this variant is absent fromPitohuiand poison frog Navs, incurs a strong cost that compromises channel function, and fails to produce BTX-resistant channels when tested in the context of poison frog Navs. We further show that captive-raised poison frogs are BTX resistant, even though they bear BTX-sensitive Navs. Hence, our data refute the hypothesis that BTX autoresistance is rooted in Navmutations and instead suggest that more generalizable mechanisms such as toxin sequestration act to protect BTX-bearing species from autointoxication.
Genetic Circuits Combined with Machine Learning Provides Fast Responding Living Sensors
Authors: Saltepe Behide , Bozkurt Eray Ulaş , Güngen Murat Alp , Çiçek A. Ercüment , Şeker Urartu Özgür Şafak
Published: October 2020

Whole cell biosensors (WCBs) have become prominent in many fields from environmental analysis to biomedical diagnostics thanks to advanced genetic circuit design principles. Despite increasing demand on cost effective and easy-to-use assessment methods, a considerable amount of WCBs retains certain drawbacks such as long response time, low precision and accuracy. Furthermore, the output signal level does not correspond to a specific analyte concentration value but shows comparative quantification. Here, we utilized a neural network-based architecture to improve the aforementioned features of WCBs and engineered a gold sensing WCB which has a long response time (18 h). Two Long-Short Term-Memory (LSTM)-based networks were integrated to assess both ON/OFF and concentration dependent states of the sensor output, respectively. We demonstrated that binary (ON/OFF) network was able to distinguish between ON/OFF states as early as 30 min with 78% accuracy and over 98% in 3 h. Furthermore, when analyzed in analog manner, we demonstrated that network can classify the raw fluorescence data into pre-defined analyte concentration groups with high precision (82%) in 3 h. This approach can be applied to a wide range of WCBs and improve rapidness, simplicity and accuracy which are the main challenges in synthetic biology enabled biosensing.
Transcriptional profiling reveals conserved and species-specific plant defense responses during the interaction of the early divergent plantPhyscomitrium patenswithBotrytis cinerea
Authors: Reboledo Guillermo , Agorio Astrid , Vignale Lucía , Batista-García Ramón Alberto , De León Inés Ponce
Published: October 2020

Bryophytes were among the first plants that colonized earth and they evolved key defense mechanisms to counteract microbial pathogens present in the new environment. Although great advances have been made on pathogen perception and subsequent defense activation in angiosperms, limited information is available in early divergent land plants. In this study, a transcriptomic approach uncovered the molecular mechanisms underlying the defense response of the bryophytePhyscomitrium patensagainst the important plant pathogenBotrytis cinerea. A total of 3.072 differentially expressed genes were significantly affected duringB. cinereainfection, including genes encoding proteins with known function in angiosperm immunity and involved in pathogen perception, signaling, transcription, hormonal signaling, metabolic pathways such as shikimate and phenylpropanoid, and proteins with diverse role in defense against biotic stress. Similarly as in other plants,B. cinereainfection leads to downregulation of genes involved in photosynthesis and cell cycle progression. These results highlight the existence of evolutionary conserved defense responses to pathogens throughout the green plant lineage, suggesting that they were probably present in the common ancestors of land plants. Moreover, several genes acquired by horizontal transfer from prokaryotes and fungi, and a high number ofP. patens-specific orphan genes were differentially expressed duringB. cinereainfection, indicating that they are part of the moss immune response and probably played an ancestral role related to effective adaptation mechanisms to cope with pathogen invasion during the conquest of land.

Key Message

Evolutionary conserved defense mechanisms present in extant bryophytes and angiosperms, as well as moss-specific defenses are part of the immune response of the early divergent land plantPhyscomitrium patens.
Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness
Authors: Oropeza E , Seker S , Carrel S , Mazumder A , Jimenez A , VandenHeuvel SN , Noltensmeyer DA , Punturi NB , Lei JT , Lim B , Raghavan S , Bainbridge MN , Haricharan S
Published: October 2020

Cell cycle dysregulation is prerequisite for cancer formation. However, it is unknown whether the mode of dysregulation affects disease characteristics. Here, we conduct comprehensive analyses of cell cycle checkpoint dysregulation events in breast cancer using patient data complemented by experimental investigations in multiple model systems: genetically-engineered mice, patient-derived xenografts, biomatrices, and cell lines. We find thatATMmutation predisposes the diagnosis of primary estrogen receptor (ER)+/human epidermal growth factor (HER)2- cancer in older women. Conversely, CHK2 dysregulation induces formation of metastatic, premenopausal ER+/HER2- breast cancer (p=0.001) that is treatment-resistant (HR=6.15, p=0.01). Lastly, while mutations inATRalone are rare,ATR/TP53co-mutation is 12-fold enriched over expected in ER+/HER2- disease (p=0.002) and associates with metastatic progression (HR=2.01, p=0.006). Concordantly, ATR dysregulation induces metastatic phenotypes inTP53mutant, but not wild-type, cells. These results newly identify a role for distinct cell cycle dysregulation events in determining cancer subtype, metastatic potential, and treatment responsiveness.

Statement of Significance

These findings reframe the paradigm of cancer classification by demonstrating that cell cycle dysregulation decisions during malignant transformation can causally direct the type of cancer that evolves, its metastatic potential, and treatment responsiveness. These results provide rationale for delineating mode of checkpoint kinase dysregulation to improve diagnostic and therapeutic choices.
Unsupervised Learning of Brain State Dynamics during Emotion Imagery using High-Density EEG
Authors: Hsu Sheng-Hsiou , Lin Yayu , Onton Julie , Jung Tzyy-Ping , Makeig Scott
Published: October 2020

Here we assume that emotional states correspond to functional dynamic states of brain and body, and attempt to characterize the appearance of these states in high-density scalp electroencephalographic (EEG) recordings acquired from 31 participants during 1-2 hour sessions, each including fifteen 3-5 min periods of self-induced emotion imagination using the method of guided imagery. EEG offers an objective and high-resolution measurement of whatever portion of cortical electrical dynamics is resolvable from scalp recordings. Despite preliminary progress in EEG-based emotion decoding using supervised machine learning methods, few studies have applied data-driven, unsupervised decomposition approaches to investigate the underlying EEG dynamics by characterizing brain temporal dynamics during emotional experience. This study applies an unsupervised approach – adaptive mixture independent component analysis (adaptive mixture ICA, AMICA) that learns a set of ICA models each accounted for portions of a given multi-channel EEG recording. We demonstrate that 20-model AMICA decomposition can identify distinct EEG patterns or dynamic states active during each of the fifteen emotion-imagery periods. The transition in EEG patterns revealed the time-courses of brain-state dynamics during emotional imagery. These time-courses varied across emotions: “grief” and “happiness” showed more abrupt transitions while “contentment” was nearly indistinguishable from the preceding rest period. The spatial distributions of independent components (ICs) of the AMICA models showed higher similarity within-subject across emotions than within-emotion across subjects. No significant differences in IC distributions were found between positive and negative emotions. However, significant changes in IC distributions during emotional imagery compared to rest were identified in brain areas such as the left prefrontal cortex, the posterior cingulate cortex, the motor cortex, and the visual cortex. The study demonstrates the feasibility of AMICA in modeling high-density and nonstationary EEG and its utility in providing data-driven insights into brain state dynamics during self-paced emotional experiences, which have been difficult to measure. This approach can advance our understanding of highly dynamical emotional processes and improve the performance of EEG-based emotion decoding for affective computing and human-computer interaction.
A Python-based optimization framework for high-performance genomics
Authors: Shajii Ariya , Numanagić Ibrahim , Leighton Alexander T. , Greenyer Haley , Amarasinghe Saman , Berger Bonnie
Published: October 2020

Exponentially-growing next-generation sequencing data requires high-performance tools and algorithms. Nevertheless, the implementation of high-performance computational genomics software is inaccessible to many scientists because it requires extensive knowledge of low-level software optimization techniques, forcing scientists to resort to high-level software alternatives that are less efficient. Here, we introduce Seq—a Python-based optimization framework that combines the power and usability of high-level languages like Python with the performance of low-level languages like C or C++. Seq allows for shorter, simpler code, is readily usable by a novice programmer, and obtains significant performance improvements over existing languages and frameworks. We showcase and evaluate Seq by implementing seven standard, widely-used applications from all stages of the genomics analysis pipeline, including genome index construction, finding maximal exact matches, long-read alignment and haplotype phasing, and demonstrate its implementations are up to an order of magnitude faster than existing hand-optimized implementations, with just a fraction of the code. By enabling researchers of all backgrounds to easily implement high-performance analysis tools, Seq further opens the door to the democratization and scalability of computational genomics.
Fluid Intelligence and Time Management and Artificial Neural Networks
Authors: Tiitto Markus Ville , Lodder Robert A.
Published: October 2020

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. Our lab is currently conducting a pilot study to assess the effects of the online game Minecraft as a therapeutic video game (TVG) to train executive function deficits in children with ADHD. The effect of the TVG intervention in combination with stimulants is being investigated to develop a drug-device combination therapy that can address both the dopaminergic dysfunction and executive function deficits present in ADHD. Although the results of this study will be used to guide the clinical development process, additional guidance for the optimization of the executive function training activities will be provided by a computational model of executive functions built with artificial neural networks (ANNs). This model uses ANNs to complete virtual tasks resembling the executive function training activities that the study subjects practice in the Minecraft world, and the schedule of virtual tasks that result in maximum improvements in ANN performance on these tasks will be investigated as a method to inform the selection of training regimens in future clinical studies. This study first proposes the use of recurrent neural networks to model the fluid intelligence executive function. This model is then combined with a previously developed model using convolutional neural networks to model working memory and prepotent impulsivity to produce virtual “subjects” who complete a computational simulation of a Time Management task that requires the use of both of these executive functions to complete. The capability of this model to produce groups of virtual “subjects” with significantly different levels of performance on the Time Management task is demonstrated.
Value Shapes Abstraction During Learning
Authors: Cortese Aurelio , Yamamoto Asuka , Hashemzadeh Maryam , Sepulveda Pradyumna , Kawato Mitsuo , De Martino Benedetto
Published: October 2020

The human brain excels at constructing and using abstractions, such as rules, or concepts. Here, in two fMRI experiments, we demonstrate a mechanism of abstraction built upon the valuation of sensory features. Human volunteers learned novel association rules linking simple visual features. Mixture-of-experts reinforcement learning algorithms revealed that, with learning, high-value abstract representations increasingly guided participants’ behaviour, resulting in better choices and higher subjective confidence. We also found that the brain area computing value signals - the ventromedial prefrontal cortex – prioritized and selected latent task elements during abstraction, both locally and through its connection to the visual cortex. Such coding scheme predicts a causal role for valuation: in a second experiment, we used multivoxel neural reinforcement to test for the causality of feature valuation in the sensory cortex as a mechanism of abstraction. Tagging the neural representation of a task’s feature with rewards evoked abstraction-based decisions. Together, these findings provide a new interpretation of value as a goal-dependent, key factor in forging abstract representations.
Allosteric regulation in CRISPR/Cas1-Cas2 protospacer acquisition mediated by DNA in association with Cas2
Authors: Long Chunhong , Dai Liqiang , E Chao , Da Lin-Tai , Yu Jin
Published: October 2020

Cas1 and Cas2 are highly conserved proteins across CRISPR-Cas systems and play a significant role in protospacer acquisition. Here we study the protospacer (or ps) DNA binding, recognition, and response to cleavage on the protospacer-adjacent-motif complementary sequence or PAMc by Cas1-Cas2, implementing all-atom molecular dynamics simulations. First, we noticed that two active sites of Cas1&1’ bind asymmetrically to two identical PAMc in the simulation. For psDNA containing only one PAMc to be recognized, it is then found that the non-PAMc association site remains destabilized until after the bound PAMc being cleaved. Thus, correlation appears to exist between the two active sites, which can be allosterically mediated by psDNA and Cas2&2’ in bridging. To substantiate such findings, we further simulated Cas1-Cas2 in complex with synthesized psDNA sequences psL and psH, which have been measured with low and high efficiency in acquisition, respectively. Notably, such inter-site correlation becomes largely enhanced for Cas1-Cas2 in complex with psH, and remains low with psL. Hence, our studies demonstrate that PAMc recognition and cleavage in one active site of Cas1-Cas2 allosterically regulates non-PAMc association/reaction in the other site, and such allosteric regulation is mediated by non-catalytic Cas 2 and DNA protospacer in acquisition.
Father-child dyads exhibit unique inter-subject synchronisation during co-viewing of animation video stimuli
Authors: Azhari Atiqah , Bizzego Andrea , Esposito Gianluca
Published: October 2020

Inter-subject synchronisation reflects the entrainment of two individuals to each other’s brain signals during passive joint tasks. Within the parent-child dyad, the temporal coordination of signals indicates an attunement to each other’s emotional states. Despite the ubiquity with which parents and their children watch screen media together, no study has investigated intersubject synchronisation in father-child dyads during such a co-viewing activity. The present study examined whether father-child dyads would exhibit unique inter-subject synchronisation during co-viewing of narrative visual scenes that is unique to the dyad and hence would not be observed in control dyads (i.e. randomly paired signals). Hyperscanning fNIRS was used to record the prefrontal cortex (PFC) signals of 29 fathers and their preschool-aged children (11 girls, 18 boys) as each pair engaged in a typical activity of watching children’s shows together. Three 1-min video clips from “Brave”, “Peppa Pig” and “The Incredibles” were presented to each dyad and children’s ratings of video positivity and familiarity were obtained afterwards. PFC activity was analysed according to four clusters: medial left, medial right, frontal left and frontal right clusters. Results from synchrony analyses demonstrated that true father-child dyads showed significantly greater inter-subject synchronisation than control dyads, especially in the medial left cluster during the emotionally arousing conflict scene. Dyads with older fathers displayed less synchrony and older fathers, compared to younger ones, were also found to exhibit greater activity in the frontal right cluster. These findings point to a unique inter-subject synchronisation that exists in father-child relationships during shared co-viewing of narrative scenes which could be potentially modulated by parental age.
Primary cilia formation does not rely on WNT/β-catenin signaling
Authors: Bernatik Ondrej , Paclikova Petra , Kotrbova Anna , Bryja Vitezslav , Cajanek Lukas
Published: October 2020

Primary cilia act as crucial regulators of embryo development and tissue homeostasis. They are instrumental for modulation of several signaling pathways, including Hedgehog, WNT, and TGF-β. However gaps exist in our understanding of how cilia formation and function is regulated.

Recent work has implicated WNT/β-catenin signaling pathway in the regulation of ciliogenesis, yet the results are conflicting. One model suggests that WNT/β-catenin signaling negatively regulates cilia formation, possibly via effects on cell cycle. In contrast second model proposes a positive role of WNT/β-catenin signaling on cilia formation, mediated by the re-arrangement of centriolar satellites in response to phosphorylation of the key component of WNT/β-catenin pathway, β-catenin.

To clarify these discrepancies, we investigated possible regulation of primary cilia by the WNT/β-catenin pathway in cell lines (RPE-1, NIH3T3, HEK293) commonly used to study ciliogenesis. We used WNT3a to activate or LGK974 to block the pathway, and examined initiation of ciliogenesis, cilium length, and percentage of ciliated cells. We show that the treatment by WNT3a has no- or lesser inhibitory effect on cilia formation. Importantly, the inhibition of secretion of endogenous WNT ligands using LGK974 blocks WNT signaling but does not affect ciliogenesis. Finally, using knock-out cells for key WNT pathway components, namely DVL1/2/3, LRP5/6 or AXIN1/2 we show that neither activation nor deactivation of the WNT/β-catenin pathway affects the process of ciliogenesis.

These results suggest that WNT/β-catenin-mediated signaling is not generally required for efficient cilia formation. In fact, activation of the WNT/β-catenin pathway in some systems seems to moderately suppress ciliogenesis.
Acetylation of conserved lysines fine-tune mitochondrial malate dehydrogenase activity in land plants
Authors: Balparda Manuel , Elsässer Marlene , Badia Mariana B. , Giese Jonas , Bovdilova Anastassia , Hüdig Meike , Reinmuth Lisa , Schwarzländer Markus , Finkemeier Iris , Schallenberg-Rüdinger Mareike , Maurino Veronica G.
Published: October 2020

Plants need to rapidly and flexibly adjust their metabolism to changes of their immediate environment. Since this necessity results from the sessile lifestyle of land plants, key mechanisms for orchestrating central metabolic acclimation are likely to have evolved early. Here, we explore the role of lysine acetylation as a posttranslational modification to directly modulate metabolic function. We generated a lysine acetylome of the mossPhyscomitrium patensand identified 638 lysine acetylation sites, mostly found in mitochondrial and plastidial proteins. A comparison with available angiosperm data pinpointed lysine acetylation as a conserved regulatory strategy in land plants. Focusing on mitochondrial central metabolism, we functionally analyzed acetylation of malate dehydrogenase (mMDH), which acts as a hub of plant metabolic flexibility. InP. patensmMDH1, we detected a single acetylated lysine located next to one of the four acetylation sites detected inArabidopsis thalianamMDH1. We assessed the kinetic behavior of recombinantA. thalianaandP. patensmMDH1 with site-specifically incorporated acetyl-lysines. Acetylation ofA. thalianamMDH1 at K169, K170, and K334 decreases its oxaloacetate reduction activity, while acetylation ofP. patensmMDH1 at K172 increases this activity. We found modulation of the malate oxidation activity only inA. thalianamMDH1, where acetylation of K334 highly activated it. Comparative homology modelling of MDH proteins revealed that evolutionarily conserved lysines serve as hotspots of acetylation. Our combined analyses indicate lysine acetylation as a common strategy to fine-tune the activity of central metabolic enzymes with likely impact on plant acclimation capacity.

Significance statement

We explore the role of lysine acetylation as a mechanism to directly modulate mitochondrial metabolism in land plants by generating the lysine acetylome of the mossPhyscomitrium patensand comparing with available angiosperm data. We found acetylation of evolutionarily conserved lysines as a strategy to fine-tune the activity of mitochondrial malate dehydrogenase in a species-dependent molecular context.
Unravelling the crystal structure of Nd5.8WO12−δ and Nd5.7W0.75Mo0.25O12−δ mixed ionic electronic conductors
Authors: Scherb Tobias , Fantin Andrea , Checchia Stefano , Stephan-Scherb Christiane , Escolástico Sonia , Franz Alexandra , Seeger Janka , Meulenberg Wilhelm A. , d'Acapito Francesco , Serra José M.
Published: October 2020

Mixed ionic electronic conducting ceramics Nd6−y
WO12−δ (δ is the oxygen deficiency) provide excellent stability in harsh environments containing strongly reactive gases such as CO2, CO, H2, H2O or H2S. Due to this chemical stability, they are promising and cost-efficient candidate materials for gas separation, catalytic membrane reactors and protonic ceramic fuel cell technologies. As in La6−y
WO12−δ, the ionic/electronic transport mechanism in Nd6−y
WO12−δ is expected to be largely controlled by the crystal structure, the conclusive determination of which is still lacking. This work presents a crystallographic study of Nd5.8WO12−δ and molybdenum-substituted Nd5.7W0.75Mo0.25O12−δ prepared by the citrate complexation route. High-resolution synchrotron and neutron powder diffraction data were used in combined Rietveld refinements to unravel the crystal structure of Nd5.8WO12−δ and Nd5.7W0.75Mo0.25O12−δ. Both investigated samples crystallize in a defect fluorite crystal structure with space group Fm
3
m and doubled unit-cell parameter due to cation ordering. Mo replaces W at both Wyckoff sites 4a and 48h and is evenly distributed, in contrast with La6−y
WO12−δ. X-ray absorption spectroscopy as a function of partial pressure pO2 in the near-edge regions excludes oxidation state changes of Nd (Nd3+) and W (W6+) in reducing conditions: the enhanced hydrogen permeation, i.e. ambipolar conduction, observed in Mo-substituted Nd6−y
WO12−δ is therefore explained by the higher Mo reducibility and the creation of additional – disordered – oxygen vacancies.
Structure of tetrakis(μ-decanoato-κ2
O:O′)bis[(4-methylpyridine-κN)copper(II)], a dimeric copper(II) complex
Authors: Gogoi Monsumi , Das Birinchi Kumar
Published: October 2020

The 4-methylpyridine (4-Mepy) based dimeric copper(II) carboxylate complex [Cu2(C10H19O2)4(C6H7N)2] or [Cu2(μ-O2CC9H19)4(4-Mepy)2] crystallizes with triclinic (P\overline{1}) symmetry. The two CuII ions exhibit a distorted square-pyramidal environment and are connected into a centrosymmetric paddle-wheel dinuclear cluster [Cu...Cu = 2.6472 (8) Å] via four bridging carboxylate ligands arranged in the syn–syn coordination mode. The apical positions around the paddle-wheel copper centers are occupied by the N atoms of the 4-methylpyridine ligands. The structure exhibits disorder of the terminal alkyl carbon atoms in the decanoate chains.
A multi-criteria decision-making model for selecting curtain wall systems in office buildings
Authors: Hamida Hamza , Alshibani Adel
Published: October 2020

Purpose

The purpose of this paper is to develop a model that facilitates the evaluation and selection processes of curtain wall systems used in office buildings.

Design/methodology/approach

A comprehensive literature review and interviews with local experts were conducted to identify common types of curtain wall systems used in office buildings and their selection criteria. A questionnaire was designed and completed using multi-criteria decision-making techniques through face-to-face meetings with consultants in the Eastern Province of Saudi Arabia. The proposed model was implemented in prototype software as a proof of concept.

Findings

The results revealed that fire resistance scored the highest weighting of all the criteria. Furthermore, precast concrete cladding panels were found to be the best system for use in office buildings located in the Eastern Province of Saudi Arabia. The model validation reveals that the score for any curtain wall system varies depending on the nature of the project and that the prioritisation of criteria can vary from one practitioner to another.

Originality/value

The model captures the knowledge of professionals who are experts in the prioritisation of criteria for selecting curtain wall systems. The research design presented expands the boundaries of knowledge of the relevant literature, through demonstrating a conceptual framework incorporating different techniques into a computerised model. It has practical implications through presenting a systematic procedure for developing and adopting a computerised decision-making tool, which aligns experts’ professional practice and requirements, for use in selecting fragmented options.
The impact of team potency and leadership member exchange on expatriate creative work involvement
Authors: Almazrouei Hanan Saber , Zacca Robert , Alfayez Noura
Published: October 2020

Purpose

The purpose of this study is to examine whether team potency moderates the effect of the leader member exchange (LMX) on the expatriate's creative work involvement such that the effect of leader member exchange on creative work involvement becomes less when team potency is high.

Design/methodology/approach

Data were gathered via a printed survey instrument, using a purposive sampling approach and administered directly to 150 expatriate (non-Emirate nationals) employees located in the Jabal Ali Dubai Free Zone of the United Arab Emirates (UAE).

Findings

Our findings indicate that the higher the level of team potency the less the effect of LMX on expatriate creative work involvement.

Practical implications

The findings suggest that, team potency, which is an asset in certain situations, can be a liability suppressing the effect of LMX on the expatriate employees creative work involvement. Expatriate employees experiencing satisfaction and fulfillment through the leadership exchange feel sufficiently empowered in their abilities to engage in creative work behaviors.

Originality/value

Testing a theoretical model within the intranational cultural diversity of an expatriate workforce may be a stronger source of diversity than other sources, providing for an original theoretical contribution to the extant literature. Moreover, the UAE, with its prominent network of expatriate employment integrated within the national economy presents a highly relevant contextual environment in which to study expatriate behavior.
COVID-19 economic shocks and fiscal policy options for Ghana
Authors: Dzigbede Komla D. , Pathak Rahul
Published: October 2020

Purpose

This article examines the fiscal challenges the coronavirus pandemic poses in African countries, using Ghana as a case study and summarizes the country's immediate monetary and fiscal responses to the pandemic. The article also discusses the potential impacts of coronavirus-related shocks on the Ghana economy and policy options the national government may pursue to counteract the pandemic's adverse long-term effects.

Design/methodology/approach

The article uses daily and monthly economic indicators to assess the immediate impact of the pandemic on Ghana's economy. The article also uses latest data from the Ghana Living Standards Survey (GLSS) to simulate potential shocks to the economy related to the coronavirus crisis and examines the outcomes from a potential government response that expands spending on an existing direct social assistance program.

Findings

The authors find that the coronavirus pandemic is associated with a significant increase in Ghana's poverty measures over time, and an expansion in government spending under an existing cash transfer program would partly offset the economic shocks related to the crisis and improve outcomes for poverty and inequality. The authors also argue that other well-targeted expenditure and revenue policies will support long-term economic resilience.

Research limitations/implications

The research suggests that a temporary expansion of the existing program of direct cash payments to poor households may be an effective social protection policy, as are well-targeted revenue and spending policies that support economic recovery and long-term fiscal sustainability.

Practical implications

The findings imply that while the pandemic might cause severe shocks in the economy, well-targeted spending and revenue policies that are anchored in sound macroeconomic management can promote economic resilience and long-term fiscal sustainability.

Social implications

Public managers must ensure that national policy responses to the coronavirus pandemic consider socio-economic indicators, such as poverty and income inequality.

Originality/value

The authors present research that uses novel household-level data and an evidence-based microsimulation framework to articulate potential public policy strategies that can guide national responses to, and recovery from, the coronavirus pandemic.
Luxury brands’ use of CSR and femvertising: the case of jewelry advertising
Authors: Pankiw Stephanie A. , Phillips Barbara J. , Williams David E.
Published: October 2020

Purpose

Luxury brands seek to differentiate themselves from competitors by engaging in corporate social responsibility (CSR) practices. Although many luxury brands participate in CSR activities, it is unclear if luxury brands communicate these CSR activities to consumers. Therefore, this study aims to explore two questions: are luxury jewelry brands communicating CSR (including women’s empowerment) in their advertising? And how should luxury jewelry brands communicate CSR messages in their advertising?

Design/methodology/approach

This paper uses a content analysis of luxury jewelry print advertisements and in-depth interviews with 20 female jewelry consumers analyzed using grounded theory to construct the luxury brand CSR advertising strategies theory.

Findings

Very few (3%) of print advertisements contain CSR messages, including femvertising and the theory presents four paths for brands to consider when promoting CSR practices, namely, ethical sourcing, cause-related marketing product, a signal of product care and quality and signal of an authentic relationship with the consumer.

Practical implications

The model provides four potential CSR advertising strategies and guidelines luxury jewelry brands can use to create successful advertising campaigns.

Originality/value

Luxury jewelry advertising has not been empirically examined and the study fills gaps in the understanding of luxury brands’ communication strategies. It adds to the knowledge and theorizing of the use and appropriateness of CSR appeals in a luxury brand context.