bluuebunny/crossref_metadata_2025 huggingface dataset:
FAIR enough? A perspective on the status of nucleotide sequence data and metadata on public archives
Authors: Hassenrück Christiane , Poprick Tobias , Helfer Véronique , Molari Massimiliano , Meyer Raissa , Kostadinov Ivaylo
Published: September 2021

Knowledge derived from nucleotide sequence data is increasing in importance in the life sciences, as well as decision making (mainly in biodiversity policy). Metadata standards have been established to facilitate sustainable sequence data management according to the FAIR principles (Findability, Accessibility, Interoperability, Reusability). Here, we review the status of metadata available for raw read Illumina amplicon and whole genome shotgun sequencing data derived from ecological metagenomic material that are accessible at the European Nucleotide Archive (ENA), as well as the compliance of the primary sequence data (fastq files) with data submission requirements. While overall basic metadata, such as geographic coordinates, were retrievable in 98% of the cases for this type of sequence data, interoperability was not always ensured and other (mainly conditionally) mandatory parameters were often not provided at all. Metadata standards, such as the ‘Minimum Information about any(x) Sequence (MIxS)’, were only infrequently used despite a demonstrated positive impact on metadata quality. Furthermore, the sequence data itself did not meet the prescribed requirements in 31 out of 39 studies that were manually inspected. To tackle the most immediate needs to improve FAIR sequence data management, we provide a list of minimal suggestions to researchers, research institutions, funding agencies, reviewers, publishers, and databases, that we believe might have a potentially large positive impact on sequence data and metadata FAIRness, which is crucial for further research and its derived applications.
Active Translation Control of CD4 T Cell Activation by Regulatory T Cells
Authors: So Lomon , Obata-Ninomiya Kazushige , Hu Alex , Muir Virginia , Takamori Ayako , Song Jing , Buckner Jane H. , Savan Ram , Ziegler Steven F.
Published: September 2021

Increased protein synthesis is a hallmark of lymphocyte activation. Regulatory T cells (Tregs) suppress the activation and subsequent effector functions of CD4 effector T cells (Teffs). However, molecular mechanisms that enforce Treg-mediated suppression in CD4 Teff are not fully clear. Control of CD4 Teff activation by Tregs has largely been defined at the transcriptional level, which does not reflect changes in post-transcriptional control. We found that Tregs suppressed activation-induced global protein synthesis in CD4 Teffs prior to cell division. We analyzed genome-wide changes in the transcriptome and translatome of activated CD4 Teffs using two independent approaches. We show that mRNAs encoding for the protein synthesis machinery are regulated at the level of translation in activated Teffs. Strikingly, Tregs suppressed global protein synthesis of CD4 Teffs by specifically inhibiting mRNAs of the translation machinery at the level of mTORC1-mediated translation control. Lastly, we found that the RNA helicase eIF4A inhibitor rocaglamide A (RocA) can suppress CD4 Teff activation in vitro to alleviate inflammatory CD4 Teff activation caused by acute Treg depletion in vivo. These data provide evidence that peripheral tolerance is enforced by Tregs through mRNA translational control in CD4 Teffs. Therefore, therapeutic targeting of the protein synthesis machinery can be expected to mitigate inflammatory responses invoked by Treg loss of function.
Tracking extracellular vesicle (EV) cargo as a platform for studying EVomics, signaling, and targeting in vivo
Authors: Nikonorova Inna A. , Wang Juan , Cope Alexander L. , Tilton Peter , Power Kaiden M. , Walsh Jonathon D. , Akella Jyothi S. , Krauchunas Amber R. , Shah Premal , Barr Maureen M.
Published: September 2021

Extracellular vesicle (EV)-based signaling is a challenge to study, due to EV small size, heterogeneity, and limited information on cargo content in vivo. We present Caenorhabditis elegans as a discovery platform that allows single EV tracking from source to target tissue in living animals. We enriched ciliary EVs using GFP-tagged PKD-2 cargo followed by mass spectrometry analysis to identify 2,888 cargo candidates. By integrating our dataset with single-cell transcriptomic data, we identified EV cargo produced by individual neurons and other cell and tissue types. A single cilium produces multiple EVs with distinct protein content. Ciliary EVs carry nucleic acid binding proteins. We observed transfer of EV cargo from the male reproductive tract to the hermaphrodite uterus during mating, a direct demonstration of animal-to-animal EV targeting.

One-Sentence Summary

Here we present a discovery platform for studying animal extracellular vesicle composition and biogenesis.
DuoxandJak/Statsignalling influence disease tolerance in Drosophila duringPseudomonas entomophilainfection
Authors: Prakash Arun , Monteith Katy M. , Bonnet Mickael , Vale Pedro F.
Published: September 2021

Disease tolerance describes an infected host’s ability to maintain health independently of the ability to clear microbe loads. The Jak/Stat pathway plays a pivotal role in humoral innate immunity by detecting tissue damage and triggering cellular renewal, making it a candidate tolerance mechanism. Here, we find that inDrosophila melanogasterinfected withPseudomonas entomophiladisruptingROS-producingdual oxidase (duox) or the negative regulator of Jak/StatSocs36E, render male flies less tolerant. Another negative regulator of Jak/Stat,G9a- which has previously been associated with variable tolerance of viral infections – did not affect the rate of mortality with increasing microbe loads compared to flies with functionalG9a, suggesting it does not affect tolerance of bacterial infection as in viral infection. Our findings highlight that ROS production and Jak/Stat signalling influence the ability of flies to tolerate bacterial infection sex-specifically and may therefore contribute to sexually dimorphic infection outcomes inDrosophila.
SCONCE: A method for profiling Copy Number Alterations in Cancer Evolution using Single Cell Whole Genome Sequencing
Authors: Hui Sandra , Nielsen Rasmus
Published: September 2021

Copy number alterations are a significant driver in cancer growth and development, but remain poorly characterized on the single cell level. Although genome evolution in cancer cells is Markovian through evolutionary time, copy number alterations are not Markovian along the genome. However, existing methods call copy number profiles with Hidden Markov Models or change point detection algorithms based on changes in observed read depth, corrected by genome content, and do not account for the stochastic evolutionary process. We present a theoretical framework to use tumor evolutionary history to accurately call copy number alterations in a principled manner. In order to model the tumor evolutionary process and account for technical noise from low coverage single cell whole genome sequencing data, we developed SCONCE, a method based on a Hidden Markov Model to analyze read depth data from tumor cells using matched normal cells as negative controls. Using a combination of public datasets and simulations, we show SCONCE accurately decodes copy number profiles, with broader implications for understanding tumor evolution. SCONCE is implemented in C++11 and is freely available from https://github.com/NielsenBerkeleyLab/sconce.
Mice With Monoallelic GNAO1 Loss Exhibit Reduced Inhibitory Synaptic Input To Cerebellar Purkinje Cells
Authors: Feng Huijie , Yuan Yukun , Williams Michael R. , Roy Alex J. , Leipprandt Jeffery , Neubig Richard R.
Published: September 2021

GNAO1 encodes Gαo, a heterotrimeric G protein alpha subunit in the Gi/o family. In this report, we used a Gnao1 mouse model “G203R” previously described as a “gain-of-function” Gnao1 mutant with movement abnormalities and enhanced seizure susceptibility. Here, we report an unexpected second mutation resulting in a loss-of-function Gαo protein and describe alterations in central synaptic transmission.

Whole cell patch clamp recordings from Purkinje cells (PCs) in acute cerebellar slices from Gnao1 mutant mice showed significantly lower frequencies of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) compared to WT mice. There was no significant change in sEPSCs or mEPSCs. Whereas mIPSC frequency was reduced, mIPSC amplitudes were not affected, suggesting a presynaptic mechanism of action. A modest decrease in the number of molecular layer interneurons was insufficient to explain the magnitude of IPSC suppression. Paradoxically, Gi/o inhibitors (pertussis toxin), enhanced the mutant-suppressed mIPSC frequency and eliminated the difference between WT and Gnao1 mice. While GABAB receptor regulates mIPSCs, neither agonists nor antagonists of this receptor altered function in the mutant mouse PCs. This study is the first electrophysiological investigation of the role of Gi/o protein in cerebellar synaptic transmission using an animal model with a loss-of-function Gi/o protein.

Significance Statement

This is the first report on the electrophysiological mechanisms of a movement disorder animal model with monoallelic Gnao1 loss. This study illustrates the role of Gαo protein in regulating GABA release in mouse cerebellum. This study could also facilitate the discovery of new drugs or drug repurposing for GNAO1-associated disorders. Moreover, since GNAO1 shares pathways with other genes related to movement disorders, developing drugs for the treatment of GNAO1-associated movement disorders could further the pharmacological intervention for other monogenic movement disorders.
CHEK2 SIGNALING IS THE KEY REGULATOR OF OOCYTE SURVIVAL AFTER CHEMOTHERAPY
Authors: Emori Chihiro , Boucher Zachary , Bolcun-Filas Ewelina
Published: September 2021

Radiation and chemotherapy can damage the primordial follicle reserve in female cancer patients leading to ovarian failure and infertility. Preservation of ovarian function requires treatment strategies that prevent loss of immature oocytes in primordial follicles during cancer therapy. Checkpoint kinase 2 (CHEK2) inhibition prevents loss of primordial oocytes caused by DNA damage and thus is a promising target for ovoprotective treatment against genotoxic agents. To determine which cancer treatments could benefit from ovoprotective activity of CHEK2 inhibition we investigated oocyte survival inChek2-/- mice exposed to different chemotherapy drugs. Here, we show that loss of CHEK2 function prevents elimination of primordial oocytes damaged by cisplatin, cyclophosphamide, mafosfamide, doxorubicin, and etoposide, suggesting it could be used to reduce ovarian damage caused by wide range of drugs. Using genetic knockouts we reveal a critical role for TRP53 in oocyte response to chemotherapy drugs and show that both targets of CHEK2—TAp63 and TRP53— are activated by cisplatin and cyclophosphamide. Furthermore, we show that checkpoint kinase inhibitor and radiation- and chemotherapy sensitizer AZD7762 reduces oocyte elimination after radiation and chemotherapy treatments, despite its cytotoxic effect on ovarian somatic cells. Altogether, these findings demonstrate the role for CHEK2 as the master regulator of primordial oocyte survival or death and credential its targeting for ovoprotective treatments.

SIGNIFICANCE

Chemotherapy and radiation are ovotoxic and increase the risk of premature ovarian insufficiency and infertility in women cancer survivors. Development of treatment strategies preserving ovarian function and ensuring future reproductive health of female cancer patients depends on better understanding of the mechanisms underlying ovarian toxicity caused by different chemotherapy treatments. Preservation of long-term ovarian function can only be achieved by preventing the loss of immature oocytes in primordial follicles during toxic cancer therapies. Checkpoint kinase 2 (CHEK2) inhibition is an attractive strategy for protecting ovarian reserve with a potential additional benefit of sensitizing cancer cells to radiation and chemotherapy. Using a genetic approach, we show that blocking CHEK2 function is sufficient to prevent elimination of primordial oocytes damaged by chemotherapy drugs such as cisplatin, cyclophosphamide, mafosfamide, doxorubicin and etoposide. Many chemotherapy drugs are used in combination (e.g. cyclophosphamide with doxorubicin), thus the protective effect of CHEK2 inhibition is likely to be beneficial for a broad spectrum of patient treatments.
Satellite glia are essential modulators of sympathetic neuron survival, activity, and autonomic function
Authors: Mapps Aurelia A. , Boehm Erica , Beier Corrine , Keenan William T. , Langel Jennifer , Liu Michael , Hattar Samer , Zhao Haiqing , Tampakakis Emmanouil , Kuruvilla Rejji
Published: September 2021

Satellite glia are the major glial cells in sympathetic ganglia, enveloping neuronal cell bodies. Despite this intimate association, how satellite glia contribute to sympathetic functions remain unclear. Here, we show that satellite glia are critical for metabolism, survival, and activity of sympathetic neurons and modulate autonomic behaviors in mice. Adult ablation of satellite glia results in impaired mTOR signaling, soma atrophy, reduced noradrenergic enzymes, and loss of sympathetic neurons. However, persisting neurons have elevated activity, and satellite glia-ablated mice show increased pupil dilation and heart rate, indicative of enhanced sympathetic tone. Satellite glia-specific deletion of Kir4.1, an inward-rectifying potassium channel, largely recapitulates the cellular defects observed in glia-ablated mice, suggesting that satellite glia act in part via extracellular K+buffering. These findings highlight neuron-satellite glia as functional units in regulating sympathetic output, with implications for disorders linked to sympathetic hyper-activity such as cardiovascular disease and hypertension.
High-throughput functionalization of theToxoplasmakinome uncovers a novel regulator of invasion and egress
Authors: Smith Tyler A. , Lopez-Perez Gabriella S. , Shortt Emily , Lourido Sebastian
Published: September 2021

Protein kinases regulate fundamental aspects of cell biology in all eukaryotes, making them attractive chemotherapeutic targets in Apicomplexan parasites such as the causative agents of malaria (Plasmodiumspp.) and toxoplasmosis (Toxoplasma gondii). However, the precise roles of individual parasite kinases cannot be inferred simply from sequence identity, due to rewiring of signaling pathways and the shifting repertoire of kinases across species. To systematically examine the parasite kinome, we developed a high-throughput (HiT) CRISPR-mediated tagging strategy to endogenously label all predicted cytosolic protein kinases with a synthetic sequence encoding the minimal auxin-inducible degron (mAID) linked to a fluorophore and epitope tag. The system enables the assembly of thousands of tagging vectors from synthetic sequences in a single reaction and the pooled generation of mutants to examine kinase localization and function. We examined the phenotypes associated with kinase knock-down in 1,160 arrayed clones by replica-plating in the presence or absence of auxin and found broad defects across the lytic cycle for 109 clonal isolates, assigning localizations to 39 proteins, and associating 15 kinases within 6 distinct morphological phenotypes. The relative fitness of tagged alleles was also examined by tracking the relative abundance of individual guide RNAs as parasite populations progressed through the lytic cycle, in the presence or absence of auxin. Pooled screening had a high predictive value and differentiated between delayed and acute death. Demonstrating the value of this resource, we identified a novel kinase associated with delayed death as a novel regulator of invasion and egress. We call the previously unstudied kinase Store Potentiating/Activating Regulatory Kinase (SPARK), based on its impact on intracellular Ca2+stores at key moments during the lytic cycle. Despite having a similar kinase domain to the mammalian PDK1, SPARK lacks the canonical lipid-binding domain and we find no indication SPARK positively regulates other AGC kinases, suggesting a rewiring of signaling pathways to accommodate parasite adaptations. The HiT vector screening system extends the applications of genome-wide screens into complex cellular phenotypes, providing a scalable and versatile platform for the dissection of apicomplexan cell biology.
Single Object Profiles Regression Analysis (SOPRA): A novel method for analyzing high content cell-based screens
Authors: Gurumurthy Rajendra Kumar , Pleissner Klaus-Peter , Chumduri Cindrilla , Meyer Thomas F. , Mäurer André P.
Published: September 2021

Motivation

High content screening (HCS) experiments generate complex data from multiple object features for each cell within a treated population. Usually these data are analyzed by using population-averaged values of the features of interest, increasing the amount of false positives and the need for intensive follow-up validation. Therefore, there is a strong need for novel approaches with reproducible hit prediction by identifying significantly altered cell populations.

Results

Here we describe SOPRA, a workflow for analyzing image-based HCS data based on regression analysis of non-averaged object features from cell populations, which can be run on hundreds of samples using different cell features. Following plate-wise normalization the values are counted within predetermined binning intervals, generating unique frequency distribution profiles (histograms) for each population, which are then normalized to control populations. Statistically significant differences are identified using a regression model approach. Significantly changed profiles can be used to generate a heatmap from which altered cell populations with similar phenotypes are identified, enabling detection of siRNAs and compounds with the same ‘on-target’ profile, reducing the number of false positive hits. A screen for cell cycle progression was used to validate the workflow, which identified statistically significant changes induced by siRNA-mediated gene perturbations and chemical inhibitors of different cell cycle stages.
A Drosophila Su(H) Model of Adams-Oliver Syndrome Reveals Notch Cofactor Titration as a Mechanism Underlying Developmental Defects
Authors: Gagliani Ellen K. , Gutzwiller Lisa M. , Kuang Yi , Odaka Yoshinobu , Hoffmeister Phillipp , Hauff Stefanie , Turkiewicz Aleksandra , Harding-Theobald Emily , Dolph Patrick J. , Borggrefe Tilman , Oswald Franz , Gebelein Brian , Kovall Rhett A.
Published: September 2021

Notch signaling is a conserved pathway that converts extracellular receptor-ligand interactions into changes in gene expression via a single transcription factor (CBF1/RBPJ in mammals; Su(H) in Drosophila). In humans, RBPJ variants have been linked to Adams-Oliver syndrome (AOS), a rare autosomal dominant disorder characterized by scalp, cranium, and limb defects. Here, we found that a previously described Drosophila Su(H) allele encodes a missense mutation that alters an analogous residue found in an AOS-associated RBPJ variant. Importantly, genetic studies support a model that Drosophila with a single copy of the AOS-like Su(H) allele behave in an opposing manner as flies with a Su(H) null allele due to a dominant activity of sequestering either the Notch co-activator or the antagonistic Hairless co-repressor. Consistent with this model, AOS-like Su(H) and Rbpj variants decrease DNA binding activity compared to wild type proteins, but these variants do not significantly alter protein binding to the Notch co-activator or the fly and mammalian co-repressors, respectively. Taken together, these data suggest a cofactor sequestration mechanism underlies AOS phenotypes associated with RBPJ variants, whereby a single RBPJ allele encodes a protein with compromised DNA binding activity that retains cofactor binding, resulting in Notch target gene dysregulation.
Basic reproduction numbers of three strains of mouse hepatitis viruses in mice
Authors: Nakayama Masataka , Kyuwa Shigeru
Published: September 2021

Mouse hepatitis virus (MHV) is a murine coronavirus and one of the most important pathogens in laboratory mice. Although various strains of MHV have been isolated, they are generally excreted in the feces and transmitted oronasally via aerosols and contaminated bedding. In this study, we attempted to determine the basic reproduction numbers of three strains of MHV to improve our understanding of MHV infections in mice. Five-week-old female C57BL/6J mice were inoculated intranasally with either the Y, NuU, or JHM variant strain of MHV and housed with two naive mice. After 4 weeks, the presence or absence of anti-MHV antibody in the mice was determined by the enzyme-linked immunosorbent assay. We also examined the distribution of MHV in the organs of Y, NuU, or JHM variant-infected mice. Our data suggest that the transmissibility of MHV is correlated with viral growth in the gastrointestinal tract of infected mice. To the best of our knowledge, this is the first report to address the basic reproduction numbers among pathogens in laboratory animals.
Dissection of function and recognition mechanism of M. tuberculosis ESX-1 secreted virulence factor EspC
Authors: Sharma Ruby , Kashyap Vipin K. , Kumar Manoj , Bansal Abhisheka , Saxena Ajay K.
Published: September 2021

Mycobacterium tuberculosis uses the ESAT-6 system-1/type VII (ESX-1) system for secretion of virulence proteins into the host cell, however the mechanism of virulence proteins secretion, molecular components and regulation of ESX-1 system are only partly understood. In the current study, we have analyzed the biological function and recognition mechanism between ESX-1 virulence EspC and EccA1 ATPase proteins. The EspC enters into A549 human lung carcinoma cells and exhibited cytotoxicity, as observed in MTT Assay. To understand the recognition mechanism between EspC and EccA1 ATPase, the EspC and EccA1 mutants were generated based on EspC~EccA1 interactions, as observed in molecular modeling. Binding analysis shows that EspC export arm interacts specifically to the β-hairpin insertion motif of the TPR domain of EccA1 ATPase. Mutations in these epitopes lead to significant decrease/or abolish the binding between EspC and EccA1 ATPase. Our study provides insight into biological function and recognition mechanism between EspC and EccA1 ATPase, which can be used as target to prevent EspC secretion/ or in general virulence factor secretion by mycobacterial ESX-1 system.
Coat color mismatch improves survival of a keystone boreal herbivore: energetic advantages exceed lost camouflage
Authors: Kennah Joanie L. , Peers Michael J. L. , Wal Eric Vander , Majchrzak Yasmine N. , Menzies Allyson K. , Studd Emily K. , Boonstra Rudy , Humphries Murray M. , Jung Thomas S. , Kenney Alice J. , Krebs Charles J. , Boutin Stan
Published: September 2021

Climate warming is causing asynchronies between animal phenology and environments. Mismatched traits, like coat color change mismatched with snow, can decrease survival. However, coat change does not serve a singular adaptive benefit of camouflage, and alternate coat change functions may confer advantages that supersede mismatch costs. We found that mismatch reduced rather than increased, autumn mortality risk of snowshoe hares in Yukon by 86.5 %. We suggest that the increased coat insulation and lower metabolic rates of winter acclimatized hares confer energetic advantages to white mismatched hares that reduce their mortality risk. We found that white mismatched hares forage 17-77 minutes less per day than matched brown hares between 0 and -10 °C, thus lowering their predation risk and increasing survival. We found no effect of mismatch on spring mortality risk, where mismatch occurred at warmer temperatures, suggesting a potential temperature limit where the costs of conspicuousness outweigh energetic benefits.
Purinergic receptor P2RY14 cAMP signaling regulates EGFR-driven Schwann cell precursor self-renewal and nerve tumor initiation in neurofibromatosis
Authors: Patritti-Cram Jennifer , Wu Jianqiang , Kuninaka Shinji , Coover Robert A. , Hennigan Robert F. , Rizvi Tilat A. , Chaney Katherine E. , Ravindran Ramya , Cancelas Jose A. , Spinner Robert J. , Ratner Nancy
Published: September 2021

Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by nerve tumors called neurofibromas, in which Schwann cells (SCs) lack NF1 and show deregulated RAS signaling. NF1 is also implicated in regulation of cAMP. Gene expression profiling and protein expression identified P2RY14 in SCs and SC precursors (SCPs) implicating P2RY14 as a candidate upstream regulator of cAMP in EGF-dependent SCP. We found that SCP self-renewal was reduced by genetic or pharmacological inhibition of P2RY14. In NF1 deficient SCs and malignant peripheral nerve sheath tumor (MPNST) cells, P2RY14 inhibition decreased EGFR-driven phospho-Akt and increased cAMP signaling. In a neurofibroma mouse model, genetic deletion of P2RY14 increased mouse survival, delayed neurofibroma initiation and rescued cAMP signaling. Conversely, elevation of cAMP diminished SCP number in vitro and diminished SC proliferation in neurofibroma bearing mice in vivo. These studies identify the purinergic receptor P2RY14 as a critical G-protein-coupled receptor (GPCR) in NF1 mutant SCPs and SCs and suggest roles for EGFR-GPCR crosstalk in facilitating SCP self-renewal and neurofibroma initiation via cAMP and EGFR-driven phospho-Akt.
γ-TuRCs are required for asymmetric microtubule nucleation from the somatic Golgi of Drosophila neurons
Authors: Mukherjee Amrita , Conduit Paul T.
Published: September 2021

Microtubules are polarised polymers nucleated by multi-protein γ-tubulin ring complexes (γ-TuRCs). Within neurons, microtubule polarity is plus-end-out in axons and mixed or minus-end-out in dendrites. Previously we showed that within the soma of Drosophila sensory neurons γ-tubulin localises asymmetrically to Golgi stacks, Golgi-derived microtubules grow asymmetrically towards the axon, and growing microtubule plus-ends are guided towards the axon and restricted from entering dendrite in a Kinesin-2-dependent manner (Mukerjee et al., 2020). Here we show that depleting γ-TuRCs perturbs the direction of microtubule growth from the Golgi stacks, consistent with a model for asymmetric microtubule nucleation involving γ-TuRCs and other nucleation-promoting factors. We also directly observe microtubule turning along microtubule bundles and show that depleting APC, proposed to link Kinesin-2 to plus ends, reduces microtubule turning and increases plus end growth into dendrites. These results support a model of asymmetric nucleation and guidance within the neuronal soma that helps establish and maintain overall microtubule polarity.
The retromer complex regulates C. elegans development and mammalian ciliogenesis
Authors: Xie Shuwei , Smith Ellie , Dierlam Carter , Mathew Danita , Davis Angelina , Williams Allana , Naslavsky Naava , Iyer Jyoti , Caplan Steve
Published: September 2021

The mammalian retromer is comprised of subunits VPS26, VPS29 and VPS35, and a more loosely-associated sorting nexin (SNX) heterodimer. Despite known roles for the retromer in multiple trafficking events in yeast and mammalian cells, its role in development is poorly understood, and its potential function in primary ciliogenesis remains unknown. Using CRISPR-Cas9 editing, we demonstrated that vps-26 homozygous knockout C. elegans have reduced brood sizes and impaired vulval development, as well as decreased body length which has been linked to defects in primary ciliogenesis. Since many endocytic proteins are implicated in the generation of primary cilia, we addressed whether the retromer regulates ciliogenesis in mammalian cells. We observed VPS35 localized to the primary cilium, and depletion of VPS26, VPS35 or SNX1/SNX5 led to decreased ciliogenesis. Retromer also coimmunoprecipitated with the capping protein, CP110, and was required for its removal from the mother centriole. Herein, we characterize new roles for the retromer in C. elegans development and in the regulation of ciliogenesis in mammalian cells, and suggest a novel role for the retromer in CP110 removal from the mother centriole.
Spin-resolved charge density and wavefunction refinements using MOLLYNX: a review
Authors: Souhassou Mohamed , Kiblin Iurii , Deutsch Maxime , Voufack Ariste Bolivar , Lecomte Claude , Claiser Nicolas
Published: September 2021

MOLLYNX is a new crystallographic tool developed to access a more precise description of the spin-dependent electron density of magnetic crystals, taking advantage of the richness of experimental information from high-resolution X-ray diffraction (XRD), unpolarized neutron (UND) and polarized neutron diffraction (PND). This new program is based either on the well known Hansen–Coppens multipolar model (MOLLYNX-mult) or on a new expansion over a set of atomic orbitals (MOLLYNX-orb). The main difference between the two models is the basis of the expansion: in MOLLYNX-mult the expansion is over atom centered real spherical harmonics, in MOLLYNX-orb the expansion is over a set of atomic orbitals with which mono and bicentric contributions are calculated. This new approach of MOLLYNX-orb can also be applied to nonmagnetic crystals. This paper summarizes the theoretical ground of two models and describes the first applications to organic, organometallic and inorganic magnetic materials
Layer groups: Brillouin-zone and crystallographic databases on the Bilbao Crystallographic Server
Authors: de la Flor Gemma , Souvignier Bernd , Madariaga Gotzon , Aroyo Mois I.
Published: September 2021

The section of the Bilbao Crystallographic Server (https://www.cryst.ehu.es/) dedicated to subperiodic groups contains crystallographic and Brillouin-zone databases for the layer groups. The crystallographic databases include the generators/general positions (GENPOS), Wyckoff positions (WYCKPOS) and maximal subgroups (MAXSUB). The Brillouin-zone database (LKVEC) offers k-vector tables and Brillouin-zone figures of all 80 layer groups which form the background of the classification of their irreducible representations. The symmetry properties of the wavevectors are described applying the so-called reciprocal-space-group approach and this classification scheme is compared with that of Litvin & Wike [(1991), Character Tables and Compatibility Relations of the Eighty Layer Groups and Seventeen Plane Groups. New York: Plenum Press]. The specification of independent parameter ranges of k vectors in the representation domains of the Brillouin zones provides a solution to the problems of uniqueness and completeness of layer-group representations. The Brillouin-zone figures and k-vector tables are described in detail and illustrated by several examples.
Crystal structure, Hirshfeld surface analysis and density functional theory study of 1-nonyl-3-phenylquinoxalin-2-one
Authors: Abad Nadeem , Chkirate Karim , Al-Ostoot Fares Hezam , Van Meervelt Luc , Lahmidi Sanae , Ferfra Souad , Ramli Youssef , Essassi El Mokhtar
Published: September 2021

In the title molecule, C23H28N2O, the phenyl ring is inclined to the quinoxaline ring system at a dihedral angle of 20.40 (9)°. In the crystal, C—H...O interactions between neighbouring molecules form chains along the a-axis direction. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H (70.6%), H...C/C...H (15.5%) and H...O/O...H (4.6%) interactions. The optimized structure calculated using density functional theory at the B3LYP/6–311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gap is 3.8904 eV. Part of the n-nonyl chain attached to one of the nitrogen atoms of the quinoxaline ring system shows disorder and was refined with a double conformation with occupancies of 0.604 (11) and 0.396 (11).
Crystal structure of the Al20Mn5.37Ni1.31 phase in the Al–Mn–Ni system
Authors: Hu Qifa , Wen Bin , Fan Changzeng
Published: September 2021

The intermetallic phase with composition Al20Mn5.37Ni1.31 (icosaaluminium pentamanganese nickel) was synthesized by high-temperature sintering of a mixture with initial chemical composition Al60Mn7Ni3. Al20Mn5.37Ni1.31 adopts the Co2Al5 structure type in space-group type P63/mmc, replacing the Co atoms with the transition-metal atoms Mn and Ni. Structure analysis revealed that one of the two transition-metal sites is partially occupied by Ni [refined occupancy 0.342 (2)] and the other is co-occupied by Mn and Ni with a ratio of 0.895 (14):0.105 (14). The present refined chemical composition is supported by complementary energy-dispersive X-ray fluorescence (EDX) analysis and is in agreement with the previously determined Al–Mn–Ni phase diagram [Balanetskyy et al. (2011). J. Alloys Compd, 509, 3795–3805].
Synergistic effect of polybenzoxazine/ZrO2encapsulated polyurethane nanocomposite coatings for enhanced barrier properties of steel in seawater
Authors: Xavier Joseph Raj
Published: September 2021

Purpose

The purpose of this study is to use polybenzoxazine (Pbz) functionalized ZrO2nanoparticles to synthesize polyurethane (PU)-PbZ/ZrO2nanocomposite. The results derived from the electrochemical impedance spectroscopy (EIS) and polarization studies indicated the superior anticorrosive activity of PU-Pbz/ZrO2nanocomposite coatings compared to those of plain PU coatings. The decreased corrosion current was detected on the scratch of the PU-Pbz/ZrO2nanocomposite-coated mild steel surface by scanning electrochemical microscopy (SECM) compared to other studied coatings. The superior anticorrosive and mechanical properties of the proposed nanocomposite coatings provide a new horizon in the development of high-performance anticorrosive coatings for various industries.

Design/methodology/approach

The Pbz functionalized ZrO2nanoparticles were characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX) and thermogravimetric analysis (TGA) in terms of the structural, morphological and thermal properties of these coatings. A different formulation of coatings such as PU, PU-Pbz, PU-ZrO2and PU-Pbz/ZrO2were prepared and investigated for their corrosion protection performance on mild steel in natural seawater by electrochemical techniques. The surface morphological studies were done by SEM/EDX and XRD analysis.

Findings

The superior anticorrosive property of the proposed nanocomposite coatings provides a new horizon in the development of high-performance anticorrosive coatings for various industries. Addition of Pbz wrapped ZrO2nanoparticles into the PU coating resulted in the blockage of charge transfer at the metal/electrolyte interface, which reduced the dissolution of mild steel. It was revealed from the SEM/EDX analysis that the formation of the corrosion products at the metal/electrolyte interface behaved as the passive layer which reduced the dissolution of steel.

Originality/value

The inclusion of polybenzoxazine functionalized ZrO2nanoparticles to the polyurethane coating reinforces the barrier and mechanical properties of PU-Pbz/ZrO2nanocomposite, which is due to the synergistic effect of ZrO2and Pbz.
The role of buyer-seller guanxi facets and positions in social commerce: an analysis of the buyer's perspective in Taiwan
Authors: Wu Wen-Kuei , Wu Hsiao-Chung , Lai Chih-Sung
Published: September 2021

Purpose

This study aims to explore how a buyer's perceived buyer-seller (B-S) guanxi facets (i.e. ganqing, renqing and mianzi) and guanxi positions (i.e. zi-ji-ren, shou-ren and sheng-ren) affect the seller's influence effectiveness (SIE) and purchase intention (PI) in social commerce.

Design/methodology/approach

This study conducted an online survey in three cities of Taiwan and collected a total of 364 data. The structural equation modeling and cluster analysis were used to test research hypotheses.

Findings

The results indicate that (1) each guanxi facet exerts a different and positive impact on SIE, but only one guanxi facet – renqing – helps improve PI, (2) guanxi facets can be used to predict the buyer's perceived guanxi position toward the seller, (3) the effect of guanxi facets on SIE and PI varies across B-S guanxi positions and (4) the SIE positively mediates effects of guanxi facets on the PI.

Originality/value

This study demonstrates the individual effect of each guanxi facet on SIE and PI and affirms the implicit guanxi position features guanxi facets and determines the buyer's perceived SIE and PI as well. To the best of our knowledge, these findings are rarely proposed in previous research and are beneficial for understanding the guanxi mechanism in social commerce.
Peatland microhabitat heterogeneity drives phototrophic microbe distribution and photosynthetic activity
Authors: Hamard Samuel , Küttim Martin , Céréghino Regis , Jassey Vincent E. J.
Published: September 2021

Phototrophic microbes are widespread in soils, but their contribution to soil carbon (C) uptake remains underexplored in most terrestrial systems, including C‐accreting systems such as peatlands. Here, by means of metabarcoding and ecophysiological measurements, we examined how microbial photosynthesis and its biotic (e.g., phototrophic community structure, biomass) and abiotic drivers (e.g., Sphagnum moisture, light intensity) vary across peatland microhabitats. Using a natural gradient of microhabitat conditions from pool to forest, we show that the structure of phototrophic microbial communities shifted from a dominance of eukaryotes in pools to prokaryotes in forests. We identified five groups of co‐occurring phototrophic operational taxonomic units with specific environmental preferences across the gradient. Along with such structural changes, we found that microbial C uptake was the highest in the driest and shadiest microhabitats. This study renews and improves current views on phototrophic microbes in peatlands, as the contribution of microbial photosynthesis to peatland C uptake has essentially been studied in wet microhabitats.
Risk of caesarean delivery in labour induction: a systematic review and external validation of predictive models
Authors: López‐Jiménez N , García‐Sánchez F , Hernández‐Pailos R , Rodrigo‐Álvaro V , Pascual‐Pedreño A , Moreno‐Cid M , Delgado‐Rodríguez M , Hernández‐Martínez A
Published: September 2021

Background

Despite the existence of numerous published models predicting the risk of caesarean delivery in women undergoing induction of labour (IOL), validated models are scarce.

Objectives

To systematically review and externally assess the predictive capacity of caesarean delivery risk models in women undergoing IOL.

Search strategy

Studies published up to 15 January 2021 were identified through PubMed, CINAHL, Scopus and ClinicalTrials.gov, without temporal or language restrictions.

Selection criteria

Studies describing the derivation of new models for predicting the risk of caesarean delivery in labour induction.

Data collection and analysis

Three authors independently screened the articles and assessed the risk of bias (ROB) according to the prediction model risk of bias assessment tool (PROBAST). External validation was performed in a prospective cohort of 468 pregnancies undergoing IOL from February 2019 to August 2020. The predictive capacity of the models was assessed by creating areas under the receiver operating characteristic curve (AUCs), calibration plots and decision curve analysis (DCA).

Main results

Fifteen studies met the eligibility criteria; 12 predictive models were validated. The quality of most of the included studies was not adequate. The AUC of the models varied from 0.520 to 0.773. The three models with the best discriminative capacity were those of Levine et al. (AUC 0.773, 95% CI 0.720–0.827), Hernández et al. (AUC 0.762, 95% CI 0.715–0.809) and Rossi et al. (AUC 0.752, 95% CI 0.707–0.797).

Conclusions

Predictive capacity and methodological quality were limited; therefore, we cannot currently recommend the use of any of the models for decision making in clinical practice.

Tweetable abstract

Predictive models that predict the risk of cesarean section in labor inductions are currently not applicable.
Redback spider bites in children in South Australia: A 10‐year review of antivenom effectiveness
Authors: Cocks Jane , Chu Simon , Gamage Lalith , Rossaye Sasha , Schutz Jacquie , Soon Aun Woon (Cindy)
Published: September 2021

Objective

To describe the South Australian paediatric redback spider bite experience and to examine the hypothesis that redback antivenom (RBAV) treatment in children is clinically effective.

Methods

Retrospective chart review of all children under 18 years of age presenting to the EDs of the three major paediatric or mixed hospitals in Adelaide, South Australia, with a discharge diagnosis of redback spider envenomation between 1 January 2010 and 31 March 2020. The main outcome measures include: patient and bite demographics; presenting symptoms and signs; treatment provided; clinical effects at 2 h post RBAV administration on pain, diaphoresis, blood pressure, heart rate and systemic features; overall clinical impression of RBAV effectiveness and resolution of symptoms prior to discharge.

Results

There were 256 patient encounters involving 235 patients. Latrodectism was described in one‐third (34%) of the cases. Sixty‐one patients received RBAV and in 57 (93%) patients the RBAV had good clinical effect. Two hours post RBAV administration, pain resolved in 71%, hypertension resolved in 62%, diaphoresis resolved in 43% and tachycardia resolved in 82%. There were no cases of urticaria or anaphylaxis and one case of serum sickness.

Conclusions

This retrospective review of redback spider envenomation in South Australian children over a 10‐year period has demonstrated clinical effectiveness of RBAV in paediatric patients across all age groups, observed in both clinician perceived results and measurable outcomes. RBAV remains an effective treatment for redback envenomation in children.
International and comparative human resource management: an Asia‐Pacific perspective
Authors: De Cieri Helen , Sanders Karin , Lin Caihui (Veronica)
Published: September 2021

In this paper, we review articles in the research field of international and comparative human resource management (HRM), published in Asia Pacific Journal of Human Resources since the journal’s inception in the 1960s. Our review is based on 155 articles, including 43 conceptual, opinion, editorial, and review articles, and 112 empirical studies, and examines the trends over decades by examining four major areas: 1) characteristics of the articles; 2) research topics within the international and comparative HRM; 3) theoretical frameworks; 4) country contexts; and 5) methodologies. While there have been many valuable contributions, new challenges have emerged. Based on our analysis, we provide suggestions for future research on international and comparative HRM. We call for scholars to draw attention to context and to theoretical and methodological innovation, in order to develop research with high impact and practical relevance.
Identification of the β thalassemia allele β–50 and analysis of the hematology data of carriers in a southern Chinese population
Authors: Long Ju , Liu Enqi
Published: September 2021

During a routine test, we identified a 38‐year‐old man who had a positive hematology screening result but was negative for hot spot variants of his thalassemia gene. Further analysis identified β–50 (HBB: c.‐100G>A). It was first suggested that β–50 was a β+‐thal allele, and some research groups suggested this allele was a silent β‐thal allele. To fully understand the hematological phenotype of the β–50 allele, we screened for individuals carrying β–50 in the general population and performed hematology analysis on these carriers. A real‐time PCR detection system was designed to verify samples carrying β–50. Twenty‐one thousand samples and 43 pedigree samples were screened, and 86 β–50 carriers were detected. We performed hematological analysis on 65 individuals older than 3 years who had normal serum ferritin and analyzed the data. A total of 34.62% of the β–50/βN individuals had mean cellular volume (MCV) or mean cellular hemoglobin (MCH) values slightly lower than the positive cutoff value of screening; the β–50 carriers’ Hb A2 value was slightly elevated. According to the test results, β–50 carriers have slight changes in hematology parameters, including slight decreases in MCV and MCH and slight increases in Hb A2; however, these effects do not reach the degree of traditional β+ alleles. Females with genotype β–50/β0 show a degree of decline in hematological indicators during pregnancy. Therefore, we should describe β–50 as a β++ thalassemia allele, and identification of β–50 can explain slight changes in hematological indicators in some carriers.
Increasing severity of early‐onset atopic dermatitis, but not late‐onset, associates with development of aeroallergen sensitization and allergic rhinitis in childhood
Authors: Schoos Ann‐Marie Malby , Chawes Bo Lund , Bønnelykke Klaus , Stokholm Jakob , Rasmussen Morten Arendt , Bisgaard Hans
Published: September 2021

Background

Early exposure to allergens through a defect skin barrier has been proposed as a mechanism for inducing sensitization and development of allergic diseases. We hypothesized that early‐onset, severe atopic dermatitis (AD) is associated with development of aeroallergen sensitization and allergic rhinitis.

Methods

We included 368 children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) at‐risk mother‐child cohort. AD was diagnosed prospectively based on Hanifin&Rajka's criteria and severity assessed using the Scoring Atopic Dermatitis (SCORAD) index. Early‐onset AD was defined as debut ≤1 year, late‐onset as debut from 1–6 years. Aeroallergen sensitization and allergic rhinitis were diagnosed at ages 6–7 and 12 years. Associations between early‐onset and late‐onset AD and allergy endpoints were calculated using general estimating equations (GEE) models to compute the overall odds ratios (OR) for both time points.

Results

Early‐onset AD (yes/no) and severity (SCORAD) were associated with development of aeroallergen sensitization during childhood; GEE OR = 1.68 [1.08; 2.62], p = .02 and 1.08 [1.03; 1.12], p < .001, whereas late‐onset AD showed a borderline significant association and late‐onset severity showed no association; GEE OR = 1.65 [0.92; 2.94], p = .08 and 1.01 [0.97; 1.06], p = .55. The same trend was seen for allergic rhinitis with significant association between early‐onset AD and allergic rhinitis; GEE OR = 1.56 [1.01; 2.41], p = .04 and severity; GEE OR = 1.09 [1.05; 1.13], p < .001, whereas late‐onset AD showed no association. The effects on sensitization and rhinitis of early‐onset versus late‐onset AD severity were significantly different: p‐interactionsensitization = .03 and p‐interactionrhinitis < .01.

Conclusion

Increasing severity of early‐onset AD, but not late‐onset AD, associates with aeroallergen sensitization and allergic rhinitis later in childhood.