bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear translocation of spike mRNA and protein is a novel pathogenic feature of SARS-CoV-2
Authors: Sattar Sarah , Kabat Juraj , Jerome Kailey , Feldmann Friederike , Bailey Kristina , Mehedi Masfique
Published: September 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe pathophysiology in vulnerable older populations and appears to be highly pathogenic and more transmissible than SARS-CoV or MERS-CoV [1, 2]. The spike (S) protein appears to be a major pathogenic factor that contributes to the unique pathogenesis of SARS-CoV-2. Although the S protein is a surface transmembrane type 1 glycoprotein, it has been predicted to be translocated into the nucleus due to the novel nuclear localization signal (NLS) “PRRARSV”, which is absent from the S protein of other coronaviruses. Indeed, S proteins translocate into the nucleus in SARS-CoV-2-infected cells. To our surprise, S mRNAs also translocate into the nucleus. S mRNA colocalizes with S protein, aiding the nuclear translocation of S mRNA. While nuclear translocation of nucleoprotein (N) has been shown in many coronaviruses, the nuclear translocation of both S mRNA and S protein reveals a novel pathogenic feature of SARS-CoV-2.

Author summary

One of the novel sequence insertions resides at the S1/S2 boundary of Spike (S) protein and constitutes a functional nuclear localization signal (NLS) motif “PRRARSV”, which may supersede the importance of previously proposed polybasic furin cleavage site “RRAR”. Indeed, S protein’s NLS-driven nuclear translocation and its possible role in S mRNA’s nuclear translocation reveal a novel pathogenic feature of SARS-CoV-2.
Lineage-specific oncogenes drive growth of major forms of human cancer using common downstream mechanisms
Authors: Kauko Otto , Turunen Mikko , Pihlajamaa Päivi , Häkkinen Antti , Queiroz Rayner M. L. , Pääkkönen Mirva , Ventelä Sami , Gaetani Massimiliano , Lundström Susanna , Murgia Antonio , Sahu Biswajyoti , Routila Johannes , Irjala Heikki , Griffin Julian L. , Lilley Kathryn S. , Kivioja Teemu , Hautaniemi Sampsa , Taipale Jussi
Published: September 2022

Mutations in hundreds of genes have been associated with formation of human cancer, with different oncogenic lesions prevalent in different cancer types. Yet, the malignant phenotype is simple, characterized by unrestricted growth of cells that invade neighboring healthy tissue and in many cases metastasize to distant organs. One possible hypothesis explaining this dichotomy is that the cancer genes regulate a common set of target genes, which then function as master regulators of essential cancer phenotypes, such as growth, invasion and metastasis. To identify mechanisms that drive the most fundamental feature shared by all tumors – unrestricted cell proliferation – we used a multiomic approach to identify common transcriptional and posttranslational targets of major oncogenic pathways active in different cancer types, and combined this analysis with known regulators of the cell cycle. We identified translation and ribosome biogenesis as common targets of both transcriptional and posttranslational oncogenic pathways. By combining proteomic analysis of clinical samples with functional studies of cell cultures, we also establish NOLC1 as a key node whose convergent regulation both at transcriptional and posttranslational level is critical for tumor cell proliferation. Our results indicate that lineage-specific oncogenic pathways commonly regulate the same set of targets important for growth control, revealing novel key downstream nodes that could be targeted for cancer therapy or chemoprevention.
MTG-Link: leveraging barcode information from linked-reads to assemble specific loci
Authors: Guichard Anne , Legeai Fabrice , Tagu Denis , Lemaitre Claire
Published: September 2022

Background

Local assembly with short and long reads has proven to be very useful in many applications: reconstruction of the sequence of a locus of interest, gap-filling in draft assemblies, as well as alternative allele reconstruction of large insertion variants. Whereas linked-read technologies have a great potential to assemble specific loci as they provide long-range information while maintaining the power and accuracy of short-read sequencing, there is a lack of local assembly tools for linked-read data.

Results

We present MTG-Link, a novel local assembly tool dedicated to linked-reads. The originality of the method lies in its read subsampling step which takes advantage of the barcode information contained in linked-reads mapped in flanking regions. We validated our approach on several datasets from different linked-read technologies. We show that MTG-Link is able to assemble successfully large sequences, up to dozens of Kb. We also demonstrate that the read subsampling step of MTG-Link considerably improves the local assembly of specific loci compared to other existing short-read local assembly tools. Furthermore, MTG-Link was able to fully characterize large insertion variants in a human genome and improved the contiguity of a 1.3 Mb locus of biological interest in several individual genomes of the mimetic butterfly (Heliconius numata).

Conclusions

MTG-Link is an efficient local assembly tool designed for different linked-read sequencing technologies. MTG-Link source code is available at https://github.com/anne-gcd/MTG-Link and as a Bioconda package.

Contact

anne.guichard@irisa.fr
Non-destructive collection and metabarcoding of arthropod environmental DNA remained on a terrestrial plant
Authors: Yoneya Kinuyo , Ushio Masayuki , Miki Takeshi
Published: September 2022

For the conservation and community ecology of arthropods and pest controls on terrestrial plants, survey of arthropods is a crucial step. However, efficient surveys are hindered by challenges in collecting small arthropods, and identifying the species. Environmental DNA (eDNA)-based techniques, such as eDNA metabarcording, help overcome these difficulties in aquatic systems. To apply eDNA metabarcording to terrestrial arthropods, we developed a non-destructive eDNA collection method. In this method, termed “plant flow collection,” we spray distilled or tap water, or use rainfall, which eventually flows over the surface of the plant, and is collected in a container that is set at the plant base. DNA is extracted from the filtered water samples and a DNA barcode region, such as cytochrome c oxidase subunit I (COI) gene, of the extracted DNA is amplified and sequenced using a high-throughput sequencer. We identified more than 38 taxonomic groups of arthropods at the family level, of which 7 were visually observed or artificially introduced species, whereas the other 31 groups of arthropods, including 18 species, were not observed in the visual survey. Put together, these results show that the developed method is effective for detecting the presence of arthropods in plants.
Light-induced nanoscale deformation in azobenzene thin film triggers rapid intracellular Ca2+increase via mechanosensitive cation channels
Authors: Peussa Heidi , Fedele Chiara , Tran Huy , Fadjukov Julia , Mäntylä Elina , Priimägi Arri , Nymark Soile , Ihalainen Teemu O.
Published: September 2022

Epithelial cells are in continuous dynamic biochemical and physical interaction with their extracellular environment. Ultimately, this interplay guides fundamental physiological processes. In these interactions, cells generate fast local and global transients of Ca2+ions, which act as key intracellular messengers. However, the mechanical triggers initiating these responses have remained unclear. Light-responsive materials offer intriguing possibilities to dynamically modify the physical niche of the cells. Here, we use a light-sensitive azobenzene-based glassy material that can be micropatterned with visible light to undergo spatiotemporally controlled deformations. The material allows mechanical stimulation of single cells or multicellular assemblies, offering unique opportunities for experimental mechanobiology. Real-time monitoring of consequential rapid intracellular Ca2+signals reveal that Piezo1 is the key mechanosensitive ion channel generating the Ca2+transients after nanoscale mechanical deformation of the cell culture substrate. Furthermore, our studies indicate that Piezo1 preferably responds to lateral material movement at cell-material interphase rather than to absolute topographical change of the substrate. Finally, experimentally verified computational modeling of the signaling kinetics suggests that the lateral mechanical stimulus triggers multiplexed intercellular signaling that involves Na+, highlighting the complexity of mechanical signaling in multicellular systems. These results give mechanistic understanding on how cells respond to material dynamics and deformations.
Benchmarking strategies for cross-species integration of single-cell RNA sequencing data
Authors: Song Yuyao , Miao Zhichao , Brazma Alvis , Papatheodorou Irene
Published: September 2022

The growing number of available single cell gene expression datasets from different species creates opportunities to explore evolutionary relationships between cell types across species. Cross-species integration of single-cell RNA-sequencing data has been particularly informative in this context. However, in order to do so robustly it is essential to have rigorous benchmarking and appropriate guidelines to ensure that integration results truly reflect biology. We benchmarked 28 combinations of gene homology mapping methods and data integration algorithms in a variety of biological settings. We examined the capability of each strategy to perform species-mixing of known homologous cell types and to preserve biological heterogeneity using 9 established metrics. We also developed a new biology conservation metric to address the maintenance of cell type distinguishability. Overall, scANVI, scVI and SeuratV4 methods achieved a balance between species-mixing and biology conservation. For evolutionarily distant species, including in-paralogs was beneficial. SAMap outperformed when integrating whole-body atlases between species with challenging gene homology annotation. We provided our freely available cross-species integration and assessment pipeline to help analyse new data and develop new algorithms.
Developmental trajectories of the default mode, executive control, and salience networks from the third trimester through the newborn period
Authors: Scheinost Dustin , Chang Joseph , Brennan-Wydra Emma , Lacadie Cheryl , Constable R. Todd , Chawarska Katarzyna , Ment Laura R.
Published: September 2022

Social cognition is critical to early learning. Functional imaging studies in adults and older children suggest the involvement of the default mode (DMN), executive control (ECN), and salience (SAL) networks in social cognition. These networks are vulnerable to environmental insults, and abnormalities of intra- and inter-network connectivity of the three are emerging as biomarkers of neurobehavioral disorders. However, the developmental trajectories of the DMN, ECN, and SAL across the third trimester of gestation and perinatal transition remain largely unknown. Employing resting-state functional MRI studies at 30-32, 34-36, and 40-44 weeks postmenstrual age (PMA), we tested the hypothesis that both intra- and inter-network functional connectivity in the DMN, ECN, and SAL develop across the 30-46 weeks PMA time interval in a longitudinal/cross-sectional sample of 84 fetuses and neonates. A secondary analysis addressed the impact of maternal mental health assessed at 28 weeks PMA on tri-network development from 30-46 weeks PMA. The DMN, ECN, and SAL develop across the third trimester of gestation and the first postnatal month. At the intra-network level, significant increases occurred between 36 to 44 weeks PMA for all three, with network strength values significantly different from 0 beginning at 40 weeks PMA for all. Functional connectivity increased less rapidly in the DMN than in the ECN and SAL networks, suggesting slower maturation of the network subserving social interactions. In contrast, significant inter-network DMN – ECN connectivity greater than 0 was found from 36 weeks PMA through the first postnatal month, suggesting the emergence of inter-network functional connectivity in the fetal brain. Finally, higher maternal mental health symptoms measured at the beginning of the third trimester negatively affected the developmental trajectory of the SAL network across the critical time interval of 30 weeks to 44 weeks PMA. Together, these data provide a framework to compare fetuses and neonates at risk for neurobehavioral disorders and assess the impact of the environment on the developing brain.
Pericytes control vascular stability and auditory spiral ganglion neuron survival
Authors: Zhang Yunpei , Neng Lingling , Sharma Kushal , Hou Zhiqiang , Johnson Anatasiya , Song Junha , Dabdoub Alain , Shi Xiaorui
Published: September 2022

The inner ear has a rich population of pericytes, a multi-functional mural cell essential for sensory hair cell heath and normal hearing. However, the mechanics of how pericytes contribute to the homeostasis of the auditory vascular-neuronal complex in the spiral ganglion is not yet known. In this study, using an inducible and conditional pericyte depletion mouse (PdgfrbCreERT2+/-;ROSA26iDTR+/-) model, we demonstrate, for the first time, that pericyte depletion causes loss of vascular volume and spiral ganglion neurons (SGNs) and adversely affects hearing sensitivity. Using anin vitrotrans-well co-culture system, we show pericytes markedly promote neurite and vascular branch growth in neonatal SGN explants and adult SGNs. The pericyte-controlled neural growth is strongly mediated by pericyte-released exosomes containing vascular endothelial growth factor-A (VEGF-A). Treatment of neonatal SGN explants or adult SGNs with pericyte-derived exosomes significantly enhances angiogenesis, SGN survival, and neurite growth, all of which were inhibited by a selective blocker of the VEGF receptor 2 (Flk1). Our study demonstrates that pericytes in the adult ear are critical for vascular stability and SGN health. Cross-talk between pericytes and SGNs via exosomes is essential for neuronal and vascular health and normal hearing.
Paracrine CSF1 signaling regulates macrophage migration dynamics towards ovarian cancer cells in a 3D microfluidic model that recapitulates in vivo infiltration patterns in patient-derived xenograft models
Authors: Scott Alexis L , Kulawiec Diana , Jazwinska Dorota , Zervantonakis Ioannis K
Published: September 2022

Ovarian cancer is the second most deadly gynecologic cancer in the United States, and tumorassociated macrophages in the ovarian cancer microenvironment are the most abundant immune cell type and are associated poor survival. Here, we utilize three-dimensional microfluidic assays to investigate the dynamics of macrophage infiltration towards ovarian cancer cells. Experimental results demonstrate that both ovarian cancer cell lines and patient-derived xenograft models promote the infiltration of macrophages into a 3D collagen type I extracellular matrix. Additionally, blocking CSF1 signaling reduced the number of recruited macrophages as well as migration speed, while macrophage recruitment was enhanced by addition of recombinant CSF1. We further demonstrated that results obtained with our microfluidic model are consistent with the recruitment of macrophages in vivo by patient-derived xenograft models, and that a xenograft model with high CSF1 expression showed an enhanced ability to recruit macrophages both in vitro and in vivo. These results highlight the role of CSF1 signaling in ovarian cancer, as well as the utility of microfluidic models in recapitulating the 3D ovarian cancer microenvironment.
Testing the evolutionary drivers of nitrogen-fixing symbioses in challenging soil environments
Authors: Siniscalchi Carolina M. , Kates Heather R. , Soltis Pamela S. , Soltis Douglas E. , Guralnick Robert P. , Folk Ryan A.
Published: September 2022

While the importance of root nodular symbioses (RNS) in plants has long been recognized, the ecological and evolutionary factors maintaining RNS remain obscure. RNS is associated with environmental stressors such as aridity and nitrogen-poor soils; the ability to tolerate harsh environments may provide ecological opportunities for diversification, yet, nodulators are also diverse outside these environments.

We test several environmental determinants of increased survival and enhanced diversification of RNS species, using an explicitly phylogenetic approach for the first time. We assembled the largest phylogeny of the nitrogen-fixing clade to date and a comprehensive set of abiotic niche estimates and nodulation data. We used comparative phylogenetic tools to test environmental and diversification associations.

We found that RNS is associated with warm, arid, and nitrogen-poor habitats. However, RNS was gained long before lineages entered these habitats. RNS is associated with accelerated diversification, but diversification rates are heterogeneous among nodulators, and non-legume nodulators do not show elevated diversification.

Our findings undermine the interpretation that RNS directly drove the invasion of challenging habitats, and do not support a direct relationship between soil or climate and the diversity of nodulators. Still, RNS may have been an important exaptation allowing further niche evolution.
Cyclitol secondary metabolism is a central feature ofBurkholderialeaf symbionts
Authors: Danneels Bram , Blignaut Monique , Marti Guillaume , Sieber Simon , Vandamme Peter , Meyer Marion , Carlier Aurélien
Published: September 2022

The symbioses between plants of the Rubiaceae and Primulaceae families withBurkholderiabacteria represent unique and intimate plant-bacterial relationships. Many of these interactions have been identified through PCR-dependent typing methods, but there is little information available about their functional and ecological roles. We assembled seventeen new endophyte genomes representing endophytes from thirteen plant species, including those of two previously unknown associations. Genomes of leaf endophytes belonging toBurkholderia s.l. show extensive signs of genome reduction, albeit to varying degrees. Except for one endophyte, none of the bacterial symbionts could be isolated on standard microbiological media. Despite their taxonomic diversity, all endophyte genomes contained gene clusters linked to the production of specialized metabolites, including genes linked to cyclitol sugar analog metabolism and in one instance non-ribosomal peptide synthesis. These genes and gene clusters are unique withinBurkholderia s.l. and are likely horizontally acquired. We propose that the acquisition of secondary metabolite gene clusters through horizontal gene transfer is a prerequisite for the evolution of a stable association between these endophytes and their hosts.
Vesicles driven by dynein and kinesin exhibit directional reversals without external regulators
Authors: D’Souza Ashwin I. , Grover Rahul , Monzon Gina A. , Santen Ludger , Diez Stefan
Published: September 2022

Intracellular transport along cytoskeletal filaments propelled by molecular motors ensures the targeted delivery of cargoes to their destinations. Such transport is rarely unidirectional but rather bidirectional, including intermittent pauses and directional reversals owing to the simultaneous presence of opposite-polarity motors. It has been unclear whether such a complex motility pattern results from the sole mechanical interplay between opposite-polarity motors or requires external regulators. Here, we addressed this outstanding question by reconstituting cargo motility along microtubules in vitro by attaching purified Dynein-Dynactin-BICD2 (DDB) and kinesin-3 (KIF16B) to large unilamellar vesicles. Strikingly, we found that this minimal system is sufficient to recapitulate runs, pauses and reversals similar to in vivo cargo motility. In our experiments, reversals were always preceded by vesicle pausing and the transport directionality could be tuned by the relative numbers of opposite-polarity motors on the vesicles. Unexpectedly, during all runs the vesicle velocity was not influenced by the presence of the opposing motors. To gain mechanistic insight into bidirectional transport, we developed a mathematical model which predicts that low numbers of engaged motors are critical to transition between runs and pauses. Taken together, our results suggest that motors diffusively anchored to membranous cargo transiently engage in a tug-of-war during pauses where stochastic motor attachment and detachment events can lead to directional reversals without the necessity of external regulators.
α2-ADRENERGIC MODULATION OF Ih IN ADULT-BORN GRANULE CELLS IN THE OLFACTORY BULB
Authors: Hu Ruilong , Shankar Janam , Dong Grant Z. , Villar Pablo S. , Araneda Ricardo C.
Published: September 2022

In the olfactory bulb (OB), a large population of axon-less inhibitory interneurons, the granule cells (GCs), coordinate network activity and tune the output of principal neurons, the mitral and tufted cells (MCs), through dendrodendritic interactions. Furthermore, GCs undergo neurogenesis throughout life, providing a source of plasticity to the neural network of the OB. The function and integration of GCs in the OB is regulated by several afferent neuromodulatory signals, including noradrenaline (NA), a state-dependent neuromodulator that plays a crucial role in the regulation of cortical function and task-specific decision processes. However, the mechanisms by which NA regulates GC function are not fully understood. Here, we show that NA modulates hyperpolarization-activated currents (Ih) via the activation of α2-adrenergic receptors in adult-born GCs (abGCs), thus directly acting on channels that play essential roles in regulating neuronal excitability and network oscillations in the brain. This modulation affects the dendrodendritic output of GCs leading to an enhancement of lateral inhibition onto the MCs. Furthermore, we show that NA modulates subthreshold resonance in GCs, which could affect the temporal integration of abGCs. Together, these results provide a novel mechanism by which a state-dependent neuromodulator acting on Ih can regulate GC function in the bulb.
A filamentous phage triggers antiviral responses in cystic fibrosis basal airway epithelial cells
Authors: Popescu Medeea C , Haddock Naomi L , Burgener Elizabeth B , Rojas-Hernandez Laura S , Kaber Gernot , Hargil Aviv , Bollyky Paul L , Milla Carlos E
Published: September 2022

Basal airway epithelial cells are a multipotent stem cell population which gives rise to several airway cell types. Basal cells are known to be critical to airway epithelium homeostasis and repair, and altered basal cell phenotypes have been reported in cystic fibrosis and idiopathic pulmonary fibrosis. However, very little is known about how basal cells respond to stimuli in the cystic fibrosis airway environment. Cystic fibrosis patients experience chronic infection with Pseudomonas aeruginosa and contain both high quantities of lipopolysaccharide (LPS) as well as the filamentous bacteriophage Pf produced by biofilm-state P. aeruginosa in the airway. In this study, we sought to investigate the transcriptional responses of human basal cells from both healthy controls and patients with cystic fibrosis to LPS and Pf phage. Basal cells from wildtype and cystic fibrosis donors were cultured in vitro and exposed to LPS and/or Pf phage, followed by single-cell sequencing on the 10x platform. We report that basal cells show strong antiviral responses and neutrophil chemokine production in response to Pf phage. We validate these findings in additional donors by qRT-PCR and show that Pf phage is internalized by basal cells. We also show that Pf decreases basal cell migration and proliferation. We demonstrate that Pf phage, a bacteria-infecting virus which does not replicate in mammalian cells, is taken up by basal cells and activates immune responses. Further studies are needed to determine the impact of this antiviral response to bacterial clearance.

Author Summary

When we experience a lung infection or injury, the stem cells of the airway—called basal epithelial cells—are crucial for healing the affected tissue. Basal cells proliferate and migrate to close gaps in the epithelium and replace injured and dead cells. We are also learning that basal cells can directly contribute to the immune response against lung pathogens, although little is understood about how basal cells sense viruses and bacteria, and what molecules they secrete in response. In our work, we sought to investigate the role that basal cells play in the course of an infection with the common human pathogen Pseudomonas aeruginosa. We stimulated basal cells with lipopolysaccharide (LPS), a potent immunogen produced by Pseudomonas, as well as the Pseudomonas-infecting virus Pf4. We have previously shown that Pf4, which is produced in high amounts by lung-infecting Pseudomonas, affects the immune response to this bacterium. In our work here, we show that Pf4 is recognized as a virus by basal cells and changes the transcriptional response to LPS, derailing the antibacterial immune response to Pseudomonas. These findings raise the question of whether other bacteria-infecting viruses alter immune responses, and how these viruses interact with other airway cells.
“Lead (Pb) impairs thyroid hormone mediated changes in brain development and body length in Xenopus laevis tadpoles”
Authors: Dahora Lara I. , Robinson Alayna M. , Buenaventura Christopher , Bailey Hannah , Thompson Christopher K.
Published: September 2022

Lead (Pb) poisoning during early development is associated with behavioral and cognitive deficits, but the specific mechanisms by which Pb impairs brain development are not fully understood. One potential mechanism is that Pb poisoning may impair thyroid hormone (TH)- mediated changes in brain development To address this issue, we performed experiments to assess the effects of Pb poisoning on (TH) -dependent changes in cellular and molecular mechanisms in the developing Xenopus laevis tadpole brain. We treated stage 48 tadpoles to combinations of 1000 ppb Pb bath for seven days and added one of three different concentrations of thyroxine (T4) for the final two days of treatment. We found that lead exposure decreased body length, including in T4-treated tadpoles. We also performed immuno-staining for proliferative marker pH3 and found that Pb disrupts T4-induced increases in neuronal proliferation. Finally, we used syGlass VR data visualization software to measure volume of the forebrain, midbrain, and hindbrain in 3D and found that Pb exposure impaired T4-mediated changes in brain volume. Last, we found that Pb poisoning reduced the T4-mediated increase in proliferating cell nuclear antigen (PCNA), a TH-sensitive gene. These results illustrate that Pb poisoning impairs some TH-dependent changes in the developing brain.
Transcription factors interact with RNA to regulate genes
Authors: Oksuz Ozgur , Henninger Jonathan E , Warneford-Thomson Robert , Zheng Ming M , Erb Hailey , Overholt Kalon J , Hawken Susana Wilson , Banani Salman F , Lauman Richard , Vancura Adrienne , Robertson Anne L , Hannett Nancy M , Lee Tong I , Zon Leonard I. , Bonasio Roberto , Young Richard A.
Published: September 2022

Transcription factors (TFs) orchestrate the gene expression programs that define each cell’s identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat. RNA-binding contributes to TF function by promoting the dynamic association between DNA, RNA and TF on chromatin. TF-RNA interactions are a conserved feature essential for vertebrate development and disrupted in disease. We propose that the ability to bind DNA, RNA and protein is a general property of many TFs and is fundamental to their gene regulatory function.
Uncovering the Mechanism of the Proton-Coupled Fluoride Transport in the CLCF Antiporter
Authors: Mills Kira R. , Torabifard Hedieh
Published: September 2022

Fluoride is a natural antibiotic abundantly present in the environment and, in micromolar concentrations, is able to inhibit enzymes necessary for bacteria to survive. However, as is the case with many antibiotics, bacteria have evolved resistance methods, including through the use of recently discovered membrane proteins. One such protein is the CLCF F-/H+ antiporter protein, a member of the CLC superfamily of anion-transport proteins, most notably known for their ability to transport chloride ions. While it possesses many similarities to the other CLC proteins, it also differs in several key ways, and though previous studies have examined this F- transporter, many questions are still left unanswered. To reveal details of the transport mechanism used by CLCF, we have employed molecular dynamics simulations and umbrella sampling calculations. Our results have led to several discoveries, including the mechanism of proton import and how it is able to aid in the fluoride export. Additionally, we have determined the role of the previously identified residues Glu118, Glu318, Met79, and Tyr396. This work is among the first computational studies of the CLCF F-/H+ antiporter and is the first to propose a mechanism which couples both the proton and anion transport.
Characterising modulatory effects of transcranial random noise stimulation using the perceptual template model
Authors: Gotsis Stephanie , van Boxtel Jeroen , Teufel Christoph , Edwards Mark , Christensen Bruce
Published: September 2022

Neural noise is an inherent property of all nervous systems. However, the mechanisms by which such random and fluctuating neural activity influences perception are still unclear. To elucidate the relationship between neural noise and perceptual performance we require techniques that can safely manipulate neural noise in humans. Transcranial random noise stimulation (tRNS), a form of electrical brain stimulation, has been proposed to increase neural noise according to principles of stochastic resonance (SR); where small to moderate intensities of tRNS improve performance, while higher intensities are detrimental. To date, high intensity (i.e., >2mA) tRNS effects on neural noise levels have not been directly quantified, nor have the detrimental effects proposed by SR been demonstrated in early visual processing. For this purpose, we applied a maximum current intensity of 3mA high-frequency tRNS to the visual cortex (V1) during an orientation discrimination task across increasing external visual noise levels, and fit the perceptual template model to contrast thresholds to quantify intrinsic mechanisms related to noise underlying changes in perceptual performance. We found that tRNS generally worsened perceptual performance by increasing observer’s internal noise and reducing the ability to filter external noise compared to sham. While most observers experienced detrimental effects, others demonstrated improved perceptual performance (i.e., reduced internal noise and better noise filtering). Preliminary evidence suggests that individual baseline internal noise levels may drive the observed beneficial or detrimental observer responses to tRNS. These findings have important implications for the application of tRNS to investigate the impact of internal noise and noise filtering processes on perception.
Cytoophidia safeguard binucleation of Drosophila male accessory gland cells
Authors: You Dong-Dong , Zhou Xiao-Li , Wang Qiao-Qi , Liu Ji-Long
Published: September 2022

Although most cells are mononuclear, the nucleus can exist in the form of binucleate or even multinucleate to respond to different physiological processes. The male accessory gland of Drosophila is the organ that produces semen, and its main cells are binucleate. Here we observe that CTP synthase (CTPS) forms filamentous cytoophidia in binuclear main cells, primarily located at the cell boundary. In CTPSH355A, a point mutation that destroys the formation of cytoophidia, we find that the nucleation mode of the main cells changes, including mononucleates and vertical distribution of binucleates. Although the overexpression of CTPSH355A can restore the level of CTPS protein, it will neither form cytoophidia nor eliminate the abnormal nucleation pattern. Therefore, our data indicate that there is an unexpected functional link between the formation of cytoophidia and the maintenance of binucleation in Drosophila main cells.
Structural and Immunological Similarities Between the Metacyclic and Bloodstream Form Variant Surface Glycoproteins of the African Trypanosome
Authors: Chandra Monica , Đaković Sara , Foti Konstantina , Zeelen Johan , van Straaten Monique , Aresta-Branco Francisco , Tihon Eliane , Lübbehusen Nicole , Ruppert Thomas , Glover Lucy , Papavasiliou F. Nina , Stebbins C. Erec
Published: September 2022

During infection of mammalian hosts, African trypanosomes thwart immunity using antigenic variation of the dense Variant Surface Glycoprotein (VSG) coat, accessing a large repertoire of thousands of genes and pseudogenes and switching to antigenically distinct copies. The parasite is transferred to mammalian hosts through the bite of the tsetse fly. In the salivary glands of the fly, the pathogen adopts the metacyclic form and expresses a limited repertoire of VSG genes specific to that developmental stage. It has remained unknown whether the metacyclic VSGs possess distinct properties associated with this particular and discrete phase of the parasite life cycle. We show here using bioinformatic, crystallographic, and immunological analyses of three metacyclic VSGs that they closely mirror the known classes of bloodstream form VSGs both in structure and in the immunological responses they elicit.
Travelling waves observed in MEG data can be explained by two discrete sources
Authors: Zhigalov Alexander , Jensen Ole
Published: September 2022

Growing evidence suggests that travelling waves are functionally relevant for cognitive operations in the brain. Several electroencephalography (EEG) studies report on a perceptual alpha-echo, representing the brain response to a random visual flicker, propagating as a travelling wave across the cortical surface. In this study, we ask if the propagating activity of the alpha-echo is best explained by a set of discrete sources mixing at the sensor level rather than a cortical travelling wave. To this end, we presented participants with gratings modulated by random noise and simultaneously acquired the ongoing MEG. The perceptual alpha-echo was estimated using the temporal response function linking the visual input to the brain response. At the group level, we observed a spatial decay of the amplitude of the alpha-echo with respect to the sensor where the alpha-echo was the largest. Importantly, the propagation latencies consistently increased with the distance. Interestingly, the propagation of the alpha-echoes was predominantly centro-lateral, while EEG studies reported mainly posterior-frontal propagation. Moreover, the propagation speed of the alpha-echoes derived from the MEG data was around 10 m/s, which is higher compared to the 2 m/s reported in EEG studies. Using source modelling, we found an early component in the primary visual cortex and a phase-lagged late component in the parietal cortex, which may underlie the travelling alpha-echoes at the sensor level. We then simulated the alpha-echoes using realistic EEG and MEG forward models by placing two sources in the parietal and occipital cortices in accordance with our empirical findings. The two-source model could account for both the direction and speed of the observed alpha-echoes in the EEG and MEG data. Our results demonstrate that the propagation of the perceptual echoes observed in EEG and MEG data can be explained by two sources mixing at the scalp level equally well as by a cortical travelling wave. This conclusion however does not put into question continuous travelling waves reported in intracranial recordings.
A comparison of deep-learning-based inpainting techniques for experimental X-ray scattering
Authors: Chavez Tanny , Roberts Eric J. , Zwart Petrus H. , Hexemer Alexander
Published: September 2022

The implementation is proposed of image inpainting techniques for the reconstruction of gaps in experimental X-ray scattering data. The proposed methods use deep learning neural network architectures, such as convolutional autoencoders, tunable U-Nets, partial convolution neural networks and mixed-scale dense networks, to reconstruct the missing information in experimental scattering images. In particular, the recovered pixel intensities are evaluated against their corresponding ground-truth values using the mean absolute error and the correlation coefficient metrics. The results demonstrate that the proposed methods achieve better performance than traditional inpainting algorithms such as biharmonic functions. Overall, tunable U-Net and mixed-scale dense network architectures achieved the best reconstruction performance among all the tested algorithms, with correlation coefficient scores greater than 0.9980.
HTD2: a single-crystal X-ray diffractometer for combined high-pressure/low-temperature experiments at laboratory scale
Authors: Fischer Andreas , Langmann Jan , Vöst Marcel , Eickerling Georg , Scherer Wolfgang
Published: September 2022

High-pressure (HP) X-ray diffraction experiments at low temperature (LT) require dedicated instruments as well as non-standard sample environments and measuring strategies. This is especially true when helium cryogenic temperatures below 80 K are targeted. Furthermore, only experiments on single-crystalline samples provide the prerequisites to study subtle structural changes in the p–T phase diagram under extreme LT and HP conditions in greater detail. Due to special hardware requirements, such measurements are usually in the realm of synchrotron beamlines. This contribution describes the design of an LT/HP diffractometer (HTD2) to perform single-crystal X-ray diffraction experiments using a laboratory source in the temperature range 400 > T > 2 K while applying pressures of up to 20 GPa.
Slow protein dynamics probed by time-resolved oscillation crystallography at room temperature
Authors: Aumonier Sylvain , Engilberge Sylvain , Caramello Nicolas , von Stetten David , Gotthard Guillaume , Leonard Gordon A. , Mueller-Dieckmann Christoph , Royant Antoine
Published: September 2022

The development of serial crystallography over the last decade at XFELs and synchrotrons has produced a renaissance in room-temperature macromolecular crystallography (RT-MX), and fostered many technical and methodological breakthroughs designed to study phenomena occurring in proteins on the picosecond-to-second timescale. However, there are components of protein dynamics that occur in much slower regimes, of which the study could readily benefit from state-of-the-art RT-MX. Here, the room-temperature structural study of the relaxation of a reaction intermediate at a synchrotron, exploiting a handful of single crystals, is described. The intermediate in question is formed in microseconds during the photoreaction of the LOV2 domain of phototropin 2 from Arabidopsis thaliana, which then decays in minutes. This work monitored its relaxation in the dark using a fast-readout EIGER X 4M detector to record several complete oscillation X-ray diffraction datasets, each of 1.2 s total exposure time, at different time points in the relaxation process. Coupled with in crystallo UV–Vis absorption spectroscopy, this RT-MX approach allowed the authors to follow the relaxation of the photoadduct, a thioether covalent bond between the chromophore and a cysteine residue. Unexpectedly, the return of the chromophore to its spectroscopic ground state is followed by medium-scale protein rearrangements that trigger a crystal phase transition and hinder the full recovery of the structural ground state of the protein. In addition to suggesting a hitherto unexpected role of a conserved tryptophan residue in the regulation of the photocycle of LOV2, this work provides a basis for performing routine time-resolved protein crystallography experiments at synchrotrons for phenomena occurring on the second-to-hour timescale.
Subject independent emotion recognition using EEG and physiological signals – a comparative study
Authors: Arthanarisamy Ramaswamy Manju Priya , Palaniswamy Suja
Published: September 2022

Purpose

The aim of this study is to investigate subject independent emotion recognition capabilities of EEG and peripheral physiological signals namely: electroocoulogram (EOG), electromyography (EMG), electrodermal activity (EDA), temperature, plethysmograph and respiration. The experiments are conducted on both modalities independently and in combination. This study arranges the physiological signals in order based on the prediction accuracy obtained on test data using time and frequency domain features.

Design/methodology/approach

DEAP dataset is used in this experiment. Time and frequency domain features of EEG and physiological signals are extracted, followed by correlation-based feature selection. Classifiers namely – Naïve Bayes, logistic regression, linear discriminant analysis, quadratic discriminant analysis, logit boost and stacking are trained on the selected features. Based on the performance of the classifiers on the test set, the best modality for each dimension of emotion is identified.

Findings

 The experimental results with EEG as one modality and all physiological signals as another modality indicate that EEG signals are better at arousal prediction compared to physiological signals by 7.18%, while physiological signals are better at valence prediction compared to EEG signals by 3.51%. The valence prediction accuracy of EOG is superior to zygomaticus electromyography (zEMG) and EDA by 1.75% at the cost of higher number of electrodes. This paper concludes that valence can be measured from the eyes (EOG) while arousal can be measured from the changes in blood volume (plethysmograph). The sorted order of physiological signals based on arousal prediction accuracy is plethysmograph, EOG (hEOG + vEOG), vEOG, hEOG, zEMG, tEMG, temperature, EMG (tEMG + zEMG), respiration, EDA, while based on valence prediction accuracy the sorted order is EOG (hEOG + vEOG), EDA, zEMG, hEOG, respiration, tEMG, vEOG, EMG (tEMG + zEMG), temperature and plethysmograph.

Originality/value

Many of the emotion recognition studies in literature are subject dependent and the limited subject independent emotion recognition studies in the literature report an average of leave one subject out (LOSO) validation result as accuracy. The work reported in this paper sets the baseline for subject independent emotion recognition using DEAP dataset by clearly specifying the subjects used in training and test set. In addition, this work specifies the cut-off score used to classify the scale as low or high in arousal and valence dimensions. Generally, statistical features are used for emotion recognition using physiological signals as a modality, whereas in this work, time and frequency domain features of physiological signals and EEG are used. This paper concludes that valence can be identified from EOG while arousal can be predicted from plethysmograph.
Exploring the psychological contract breach of nurses in healthcare: an exploratory study
Authors: Gulzar Saba , Hussain Kanwal , Akhlaq Ather , Abbas Zuhair , Ghauri Shagufta
Published: September 2022

Purpose

Recent advancements in the field of organizational psychology have transformed the employees’ perceptions related to the reactions of the employment relationship. The main aim of the study is to explore the consequences of psychological contracts among the nursing staff and how to provide better patient care and quality service in the health-care system as nurses play a pivotal role in the context of Pakistan. Significantly, this study attempts to bridge the research gap by exploring consequences of psychological contracts. Drawing on the social exchange theory, this study examined the psychological contracts of nurses and their reactions to the perceived violation.

Design/methodology/approach

This research adopted a qualitative method and was based on an exploratory approach. Data were collected through in-depth semi-structured interviews from 21 nurses working in public, private and charity hospitals in Karachi, Pakistan. The thematic content analysis is employed for the analysis of data by using NVivo software.

Findings

The study identified the relational and transactional elements related to the psychological contract of nurses who predominantly consisted of supervisor support, autonomy, tangible/intangible rewards and trust. The intrinsic motivation which relates to their devotion to work was found as an additional element to balance their psychological contract. This research also establishes that the psychological contract of nurses is being violated in their work settings.

Practical implications

By highlighting the importance of psychological contract breach, the findings demonstrate that health-care institutions should take measures to cope with psychological contract breach issues at the workplace.

Originality/value

This study contributes to the body of knowledge by exploring psychological contract breach. Substantially, there are rare studies conducted on psychological contract breach among nurses in developing country context (Pakistan). However, this study adds to the previous studies related to the psychological contract of nurses in the context of Pakistan by using social exchange theories. Finally, this study enables the management of healthcare to balance the psychological contract issues effectively.
An integrated building information modeling (BIM)-based lifecycle-oriented framework for sustainable building design
Authors: Kylili Angeliki , Georgali Phoebe-Zoe , Christou Petros , Fokaides Paris
Published: September 2022

Purpose

The built environment is taking enormous leaps towards its digitalization. Computer-aided tools such as building information modeling (BIM) are found in the forefront of this evolution, playing a critical role in creating the foundations for the upcoming development of smart low-carbon cities. However, the potential of BIM is still untapped – links will need to be created among the available and forthcoming methodologies under one integral operational system. The purpose of this paper is to present an integrated BIM-based life cycle-oriented framework for achieving sustainable constructions at the pre-construction phase. The developed framework represents an example of the approaches that the construction industry will need to adopt to integrate the different tools under an integrated smart city context.

Design/methodology/approach

The methodological approach follows the development of four same-volume different-configuration three-dimensional BIM designs, which are coupled with life cycle assessment (LCA) tools for establishing sustainable building design.

Findings

The results of this paper indicated that the choice of building design and shape can play a significant role in reducing the embodied energy and embodied carbon of buildings, achieving a reduction of up to 15% compared to a reference building of same volume and gross floor area.

Originality/value

The originality of this paper is found in its approach application by coupling three-dimensional BIM models with LCA data, the use of reinforcement detailing in an nD BIM study and the employment of country-specific LCA databases.