bluuebunny/crossref_metadata_2025 huggingface dataset:
Assembly and Cation-selectivity Mechanisms of Neuronal Gap Junction Channel Connexin 36 Elucidated by Cryo-EM
Authors: Mao Wenxuan , Chen Shanshuang
Published: April 2023

Electrical synapses are essential components of neural circuits. Dysfunction of electrical synapses can lead to obstacles in learning and memory. Neural signal transduction across electrical synapses is primarily mediated by a gap junction channel, Connexin 36 (Cx36), the lack of which causes impaired electrical couplings in cortical interneurons and thalamic reticular nucleus (TRN) neurons. Unique characteristics of Cx36 gap junction channel include its insensitivity in transjunctional membrane potential, as well as its preference for homomeric assembly, prone to exclude other paralogous connexins from co-assembly. However, the structural basis underlying Cx36 function and assembly remains elusive. Here, we report the cryo-EM structure of human Cx36 at 2.67 Å resolution and identified critical residues underpinning its obligatory homomeric assembly. In particular, we found non-canonical electrostatic interactions between protomers from opposing hemichannels and a steric complementary site between adjacent protomers within a hemichannel, which together offer a structural explanation for the assembly specificity in homomeric and heteromeric gap junction channels. Moreover, the narrowest restriction along the channel axis overlaps with an acidic patch, where Glu43, Asp47 and Asp48 may contribute to cation-selectivity. Also, the amino-terminal helix reported to be responsible for sensing membrane potential in other connexins was disordered in our Cx36 structure, in line with its channel activity independent of membrane potential. Together, this work elucidated the assembly mechanisms of the electrical synaptic gap junction channel, and offered possible explanations for sustained Cx36 activity upon membrane depolarization, which allows efficient action potential propagation across electrical synapses.
Multicomponent regulation of actin barbed end assembly by twinfilin, formin and capping protein
Authors: Ulrichs Heidi , Gaska Ignas , Shekhar Shashank
Published: April 2023

Living cells assemble their actin networks by regulating reactions at the barbed end of actin filaments. Formins accelerate elongation, capping protein (CP) arrests growth and twinfilin promotes depolymerization at barbed ends. How cells integrate these disparate activities within a shared cytoplasm to produce diverse actin networks, each with distinct morphologies and finely tuned assembly kinetics, is unclear. We used microfluidics-assisted TIRF microscopy to investigate how formin mDia1, CP and twinfilin influence the elongation of actin filament barbed ends. We discovered that the three proteins can simultaneously bind a barbed end in a multiprotein complex. Three-color single molecule experiments showed that twinfilin cannot bind actin filament ends occupied by formin mDia1 unless CP is present. The trimeric complex is short-lived (∼1s) and results in rapid dissociation of CP by twinfilin causing resumption of rapid formin- based elongation. Thus, the depolymerase twinfilin acts as a pro-formin factor that promotes polymerization when both CP and formin are present. While a single twinfilin binding event is sufficient to displace CP from the trimeric complex, it takes about 30 independent twinfilin binding events to remove capping protein from CP-bound barbed end. Our findings establish a new paradigm in which polymerases, depolymerases and cappers work in concert to tune cellular actin assembly.
B cells from aged mice do not have intrinsic defects in affinity maturation
Authors: Lee Jia Le , Innocentin Silvia , Silva-Cayetano Alyssa , Guillaume Stephane M. , Linterman Michelle A.
Published: April 2023

Affinity maturation, the progressive increase in serum antibody affinity after vaccination, is an essential process that contributes to an effective humoral response against vaccines and infections. Germinal centres (GCs) are key for affinity maturation, as they are where B cells undergo somatic hypermutation of their immunoglobulin genes in the dark zone, before going through positive selection in the light zone via interactions with T follicular helper cells and follicular dendritic cells. In aged mice, affinity maturation has been shown to be impaired, but whether B cell-intrinsic factors contribute to this defect remains unclear. In this study, we show that B cells from aged B cell receptor transgenic mice are able to become GC B cells, which are capable of receiving positive selection signals to a similar extent as B cells from young adult mice. Consistent with this, ageing also does not impact the ability of B cells to undergo somatic hypermutation and acquire affinity-enhancing mutations. Together, this shows that there are no B cell-intrinsic defects in affinity maturation with age when the B cell receptor repertoire is constant.
Assessing Genetic Diversity in Critically EndangeredChieniodendron hainanensePopulations within Fragmented Habitats in Hainan
Authors: Zhang Li , Zhang Hai-Li , Chen Yukai , Nizamani Mir Muhammad , Wu Tingtian , Liu Tingting , Zhou Qin
Published: April 2023

Abstract

Habitat fragmentation engenders a reduction in the geographic distribution of species, thereby rendering diminutive populations susceptible to extinction due to environmental, demographic, and genetic factors.Chieniodendron hainanense(henceforthC. hainanense) exemplifies a wild plant with extremely small populations (WPESP) and faces endangerment, necessitating urgent national conservation efforts. Elucidating the genetic diversity ofC. hainanenseis crucial for uncovering underlying mechanisms and devising protective strategies. In the present study, 35 specimens from six distinct cohort groups were genotyped utilizing genotyping-by-sequencing (GBS) and single nucleotide polymorphism (SNP) methodologies. The results indicated thatC. hainanenseexhibits limited genetic diversity. Observed heterozygosity withinC. hainanensepopulations spanned from 10.79% to 14.55%, with an average value of 13.15%. The sixC. hainanensepopulations can be categorized into two distinct groups: (1) Diaoluoshan and Baishaling, and (2) Wuzhishan, Huishan, Bawangling, and Jianfengling. The degree of genetic differentiation amongC. hainanensepopulations is relatively weak. The observed loss of diversity can be attributed to the effects of natural selection.
The vascularised chamber device significantly enhances the survival of transplanted liver organoids
Authors: Shi Denis D. , Makris Evelyn , Gerrand Yi-Wen , Lo Pu-Han , Yeoh George C. , Morrison Wayne A. , Mitchell Geraldine M. , Yap Kiryu K.
Published: April 2023

Organoid transplantation has a promising future in the treatment of liver disease, but a major limitation is the lack of guidance on the most appropriate method for transplantation that maximises organoid survival. Human induced pluripotent stem cell (hiPSC)-derived liver progenitor cell organoids were transplanted into four different transplantation sites in a mouse model of liver disease, using five organoid delivery methods. Organoids were transplanted into the vascularised chamber device established in the groin, or into the liver, spleen, and subcutaneous fat. For organoid transplantations into the liver, organoids were delivered either in Matrigel alone, or in Matrigel and a polyurethane scaffold. At 2 weeks post-transplantation, the vascularised chamber had the highest organoid survival, which was 5.1x higher than the site with second highest survival (p=0.0002), being the intra-hepatic scaffold approach. No organoid survival was observed when delivered into the liver without a scaffold, or when injected into the spleen. Very low survival occurred in transplantations into subcutaneous fat. Animals with the vascularised chamber also had the highest levels of human albumin (0.33 ± 0.09 ng/mL). This study provides strong evidence supporting the use of the vascularised chamber for future liver organoid transplantation studies, including its translation into clinical therapy.
ORFeus: A Computational Method to Detect Programmed Ribosomal Frameshifts and Other Non-Canonical Translation Events
Authors: Richardson Mary O. , Eddy Sean R.
Published: April 2023

Background

Canonical protein translation requires that ribosomes initiate translation at the correct start codon, maintain a single reading frame throughout elongation, and terminate at the first in-frame stop codon. However, ribosomal behavior can deviate at each of these steps, sometimes in a programmed manner. Certain mRNAs contain sequence and structural elements that cause ribosomes to begin translation at non-canonical start codons, shift reading frame, read through stop codons, or reinitiate on the same mRNA. These processes represent important translational control mechanisms that can allow an mRNA to encode multiple functional protein products or regulate protein expression. The prevalence of these events remains uncertain, due to the difficulty of systematic detection.

Results

We have developed a computational model to infer non-canonical translation events from ribosome profiling data.

Conclusion

ORFeus identifies known examples of alternative open reading frames and recoding events across different organisms and enables transcriptome-wide searches for novel events.
A unique cell division protein critical for the assembly of the bacterial divisome
Authors: Chu Xiao , Wang Lidong , Zhu Yiheng , Feng Zhengshan , Guan Qingtian , Song Lei , Luo Zhaoqing
Published: April 2023

Identification of unique essential bacterial genes is important for not only the understanding of their cell biology but also the development of new antimicrobials. Here we report a previously unrecognized core component of theAcinetobacter baumanniidivisome. Our results reveal that the protein, termed Aeg1 interacts with multiple cell division proteins, including FtsN, which is required for components of the divisome to localize to the midcell. We demonstrate that the FtsAE202Kand FtsBE65Amutants effectively bypassed the need of Aeg1 byA.baumannii, as did the activation variants FtsWM254Iand FtsWS274G. Our results suggest that Aeg1 is a cell division protein that arrives at the division site to initiate cell division by recruiting FtsN, which activates FtsQLB and FtsA to induce the septal peptidoglycan synthase FtsWI. The discovery of the new essential cell division protein has provided a new target for the development of antibacterial agents.
Building subtraction operators and controllers via molecular sequestration
Authors: Samaniego Christian Cuba , Qian Yili , Carleton Katelyn , Franco Elisa
Published: April 2023

We show how subtraction can be performed via a simple chemical reaction network that includes molecular sequestration. The network computes the difference between the production rate parameters of the two mutually sequestering species. We benefit from introducing a simple change of variables, that facilitates the derivation of an approximate solution for the differential equations modeling the chemical reaction network, under a time scale separation assumption that is valid when the sequestration rate parameter is sufficiently fast. Our main result is that we provide simple expressions confirming that temporal subtraction occurs when the inputs are constant or time varying. Through simulations, we discuss two sequestration-based architectures for feedback control in light of the subtraction operations they perform.
Tension sensing by FAK governs nuclear mechanotransduction, endothelial transcriptome and fate
Authors: Akhter Md Zahid , Yazbeck Pascal , Tauseef Mohammad , Anwar Mumtaz , Hossen Faruk , Datta Sayanti , Vellingiri Vigneshwaran , Joshi Jagdish Chandra , Srivastava Nityanand , Lenzini Stephen , Zhou Guangjin , Lee James , Jain Mukesh K , Shin Jae-Won , Mehta Dolly
Published: April 2023

Vascular endothelium forms a restrictive barrier to defend the underlying tissue against uncontrolled influx of circulating protein and immune cells. Mechanisms that mediate the transition from restrictive to leaky endothelium, a hallmark of tissue injury exemplified by acute lung injury (ALI), remain elusive. Using endothelial cell(EC)-Fak-/-mice, we show that FAK sensing and transmission of mechanical tension to the EC nucleus governs cell fate. In FAK- deleted EC, increased EC tension induced by Rho kinase caused tyrosine phosphorylation of nuclear envelope protein, emerin at Y74/Y95, and its localization in a nuclear cap. Activated emerin stimulated DNMT3a activity and methylation of theKLF2promoter, impairing the restrictive EC transcriptome, includingS1PR1. Inhibiting emerin phosphorylation or DNMT3a activity enabled KLF2 transcription ofS1PR1, rescuing the restrictive EC phenotype inEC-Fak-/-lungs. Thus, FAK sensing of tension transmission to the nucleus is crucial for maintaining a restrictive EC fate and lung homeostasis.
Arsenic induces two different interaction modes of SUMO with promyelocytic leukemia (PML) proteins
Authors: Hirano Seishiro , Udagawa Osamu , Kato-Udagawa Ayaka
Published: April 2023

Promyelocytic leukemia-nuclear bodies (PML-NBs) are dot-like protein assemblies and implicated in the pathogenesis of leukemia and viral infection. PML is the scaffold protein of PML-NB and its client proteins such as SUMO, DAXX, and Sp100 reside in PML-NBs. It is known that a short exposure to trivalent arsenic (As3+) induces the solubility change and the subsequent SUMOylation of PML, and the SUMO interacting motif (SIM) is not necessary for these biochemical changes. However, it has not been well studied how As3+initiates or enhances the association of SUMO with PML and the other PML-NB client proteins. Here, we report that As3+enhanced non-covalent association of PML with SUMO via the SUMO-SIM interaction which is dispensable for the solubility change and SUMOylation of PML. We also report that the As3+-induced solubility change of PML was not affected by ML792, a SUMO E1 enzyme inhibitor, even though the nuclear localization of SUMO2/3 and protein SUMOylation were halted by ML792. As3+did not change the solubility of DAXX and SUMOylation enzymes such as SAE1, UBA2, and UBC9. In contrast, As3+induced SUMOylation of Sp100 with a concomitant loss of its solubility like PML in human leukemia cell lines. Our current results indicate that both covalent and non-covalent associations of SUMO with PML are increased in As3+-exposed cells, and Sp100 may play a role in the maintenance of PML-NBs.
Clinical Methods Supporting Recognition of Early Post-Stroke Seizures: A Systematic Scoping Review
Authors: Gordon Clare , Emsley Hedley , Lightbody Catherine Elizabeth , Clegg Andrew , Harris Catherine , Harrison Joanna , Davidson Catherine Emma , Wall Jasmine , Watkins Caroline
Published: April 2023

Background

Stroke is one of the commonest cause of seizures and epilepsy and is the leading cause of epilepsy over the age of 60 (1, 2). Post-stroke seizures and epilepsy are associated with increased mortality, disability and recurrent hospital admissions (3, 4). Seizures occurring in the immediate aftermath of the acute stroke can complicate a patient’s stroke diagnosis and management or can even go undiagnosed resulting in increased risk of mortality, disability and hospital readmissions. There is limited evidence on detection, observation, diagnosis and management of early post-stroke seizures as part of acute stroke treatment.

Objectives

The objective of this series of scoping reviews is to map the extent and type of literature in relation to in-hospital early post-stroke seizures. For this paper, the specific objectives relate to the clinical methods used in the bedside identification and observation, usually performed by nurses, of early post-stroke seizures (EPSS) in adults being treated and managed for acute stroke.

Eligibility criteria

Participants included adults aged 18 years or older with acute ischaemic stroke or primary intracerebral haemorrhage and a diagnosis, or suspected diagnosis, of post-stroke seizures whilst receiving hospital care for their acute stroke.

Sources of evidence

Medline, CINAHL, Embase, and the Cochrane Library databases were searched, including papers published up to October 2021, limited to English language. A broad range of published literature was selected comprising of primary research, including case studies/case reports, conference abstracts, systematic reviews/meta-analyses, clinical guidelines and consensus statements. Reference lists of included studies were also searched.

Charting methods

A data charting table was developed by the reviewers, with key information selected for included articles. Findings have been aggregated to an overview of extent and type of evidence and identify gaps in evidence.

Results

We included two research papers, two clinical guidelines and four discussion papers. There was limited literature on clinical methods used to identify and observe acute stroke patients for seizures. We found no evaluation of different methods aimed at recognising and observing EPSS, and subsequently recommendations lacking detail and consensus on clinical processes.

Conclusion

Early post-stroke seizures are important to diagnose due to associated increases in post-stroke complications, mortality, disability and recurrent hospital admissions. Whilst the diagnostic challenge of EPSS is recognised, there is a need for research looking into how to improve the identification and observation of seizure activity in acute stroke settings.
Spatial distribution of hand-grasp motor task activity in spinal cord functional magnetic resonance imaging
Authors: Hemmerling Kimberly J. , Hoggarth Mark A. , Sandhu Milap S. , Parrish Todd B. , Bright Molly G.
Published: April 2023

Upper extremity motor paradigms during spinal cord functional magnetic resonance imaging (fMRI) can provide insight into the functional organization of the cord. Hand-grasping is an important daily function with clinical significance, but previous studies of similar squeezing movements have not reported consistent areas of activity and are limited by sample size and simplistic analysis methods. Here, we study spinal cord fMRI activation using a unimanual isometric hand-grasping task that is calibrated to participant maximum voluntary contraction (MVC). Two task modeling methods were considered: (1) a task regressor derived from an idealized block design (Ideal) and (2) a task regressor based on the recorded force trace normalized to individual MVC (%MVC). Across these two methods, group motor activity was highly lateralized to the hemicord ipsilateral to the side of the task. Activation spanned C5-C8 and was primarily localized to the C7 spinal cord segment. Specific differences in spatial distribution are also observed, such as an increase in C8 and dorsal cord activity when using the %MVC regressor. Furthermore, we explored the impact of data quantity and spatial smoothing on sensitivity to hand-grasp motor task activation. This analysis shows a large increase in number of active voxels associated with the number of fMRI runs, sample size, and spatial smoothing, demonstrating the impact of experimental design choices on motor activation.
A Nanoparticle RIG-I Agonist for Cancer Immunotherapy
Authors: Wang-Bishop Lihong , Wehbe Mohamed , Pastora Lucinda E. , Yang Jinming , Garland Kyle M. , Becker Kyle W. , Carson Carcia S. , Gibson-Corley Katherine N. , Ulkoski David , Krishnamurthy Venkata , Fedorova Olga , Richmond Ann , Pyle Anna Marie , Wilson John T.
Published: April 2023

Pharmacological activation of the retinoic acid-inducible gene I (RIG-I) pathway holds promise for increasing tumor immunogenicity and improving response to immune checkpoint inhibitors (ICI). However, the potency and clinical efficacy of 5’-triphosphate RNA (3pRNA) agonists of RIG-I is hindered by multiple pharmacological barriers, including poor pharmacokinetics, nuclease degradation, and inefficient delivery to the cytosol where RIG-I is localized. Here, we address these challenges through the design and evaluation of ionizable lipid nanoparticles (LNPs) for the delivery of 3p-modified stem-loop RNAs (SLRs). Packaging of SLRs into LNPs (SLR-LNPs) yielded surface charge-neutral nanoparticles with a size of ∼100 nm that activated RIG-I signalingin vitroandin vivo. SLR-LNPs were safely administered to mice via both intratumoral and intravenous routes, resulting in RIG-I activation in the tumor microenvironment (TME) and inhibition of tumor growth in mouse models of poorly immunogenic melanoma and breast cancer. Significantly, we found that systemic administration of SLR-LNPs reprogrammed the breast TME to enhance the infiltration of CD8+and CD4+T cells with antitumor function, resulting in enhanced response to αPD-1 ICI in an orthotopic EO771 model of triple negative breast cancer. Therapeutic efficacy was further demonstrated in a metastatic B16.F10 melanoma model, with systemically administered SLR-LNPs significantly reducing lung metastatic burden compared to combined αPD-1 + αCTLA-4 ICI. Collectively, these studies have established SLR-LNPs as a translationally promising immunotherapeutic nanomedicine for potent and selective activation of RIG-I with potential to enhance response to ICIs and other immunotherapeutic modalities.
Target Identification and Mechanistic Characterization of Indole Terpenoid Mimics: Proper Spindle Microtubule Assembly Is Essential for Cdh1-Mediated Proteolysis of CENP-A
Authors: Peng Yan , Zhang Yumeng , Fang Ruan , Jiang Hao , Lan Gongcai , Xu Zhou , Liu Yajie , Nie Zhaoyang , Ren Lu , Wang Fengcan , Zhang Shou-De , Ma Yuyong , Yang Peng , Ge Hong-Hua , Zhang Wei-Dong , Luo Cheng , Li Ang , He Weiwei
Published: April 2023

Centromere protein A (CENP-A), a histone H3 variant specific to centromeres, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. We conducted a structure-activity relationship (SAR) study of the cell cycle-arresting indole terpenoid mimic JP18 and found two more potent analogues, (+)-6-Br-JP18 and (+)-6-Cl-JP18. Tubulin was identified as a potential cellular target of these halogenated analogues by using the drug affinity responsive target stability (DARTS) based method. X-ray crystallography analysis revealed that both molecules bind to the colchicine-binding site of β-tubulin. Furthermore, we discovered that treatment of human cells with microtubule-targeting agents (MTAs), including these two compounds, led to CENP-A accumulation by destabilizing Cdh1, a co-activator of the APC/C E3 ubiquitin ligase. Our study establishes a link between microtubule dynamics and CENP-A accumulation using small-molecule tools and highlights the role of Cdh1 in CENP-A proteolysis.
Chemotactic interactions drive migration of membraneless active droplets
Authors: Dindo Mirco , Bevilacqua Alessandro , Soligo Giovanni , Monti Alessandro , Rosti Marco Edoardo , Laurino Paola
Published: April 2023

In nature, chemotactic interactions are ubiquitous and play a critical role in driving the collective behaviour of living organisms. Reproducing these interactionsin vitrois still a paramount challenge due to the complexity of mimicking and controlling cellular features, such as metabolic density, cytosolic macromolecular crowding and cellular migration, on a microorganism size scale. Here we generate enzymatically-active cell-size droplets able to move freely and, by following a chemical gradient, able to interact with the surrounding droplets in a collective manner. The enzyme within the droplets generates a pH gradient that extends outside the edge of the droplets. We discovered that the external pH gradient triggers droplet migration and controls its directionality, which is selectively towards the neighbouring droplets. Hence, by changing the enzyme activity inside the droplet we tuned the droplet migration speed. Further, we showed that these cellular-like features can facilitate the reconstitution of a simple and linear protometabolic pathway with improved overall activity. Our work suggests that simple and stable membraneless droplets can be applied to reproduce complex biological phenomena opening new perspectives as bioinspired materials and synthetic biology tools.
Quantifying Rift Valley fever virus transmission efficiency in a lamb-mosquito-lamb model
Authors: Bron Gebbiena M. , Wichgers Schreur Paul J. , Jong Mart C.M. de , Keulen Lucien van , Vloet Rianka P.M. , Koenraadt Constantianus J.M. , Kortekaas Jeroen , Bosch Quirine A. ten
Published: April 2023

Rift Valley fever virus (RVFV) is a (re)emerging mosquito-borne pathogen impacting human and animal health. How RVFV spreads through a population depends on population-level interactions between hosts and vectors (e.g., vector-to-host ratio and biting preference) and also on potential differences in individual following virus exposure (e.g., transmission efficiencies from host to vector and vice versa). Here, we estimated the probability for RVFV to transmit to naive animals by experimentally exposing lambs to a bite of an infectious mosquito (the transmission efficiency) and assessed if and how RVFV infection subsequently developed in the exposed animal.Aedes aegyptimosquitoes, previously infected via feeding on a viremic lamb, were used to expose naive lambs to the virus. Lambs were either exposed to 1-3 (low exposure) or 7-9 (high exposure) infectious mosquitoes. All lambs in the high exposure group became viremic and showed characteristic signs of Rift Valley fever within 2-4 days post exposure. In contrast, 3 out of 12 lambs in the low exposure group developed viremia and disease, with similar peaks in viremia as the high exposure group but with some heterogeneity in the onset of viremia. These results suggest that the likelihood for successful infection of a ruminant host is affected by the number of infectious mosquitoes biting, but also highlights that a lamb can be infected by a single mosquito. The per bite mosquito-to-host transmission efficiency was estimated at 28% (95% confidence interval: 15 - 47%). We subsequently combined this transmission efficiency with estimates for mosquito life traits into a Ross-McDonald mathematical model to illustrate scenarios under which major RVFV outbreaks could occur in naïve populations (i.e., R0>1). The model revealed that for efficient RVFV transmission relatively high vector-to-host ratios as well as strong feeding preference for competent hosts are required. Altogether, this study highlights the importance of experiments that mimic natural exposure to RVFV. The experiments facilitate a better understanding of the natural progression of disease and a direct way to obtain epidemiological parameters for mathematical models.
Competition between transcription and loop extrusion modulates promoter and enhancer dynamics
Authors: Platania Angeliki , Erb Cathie , Barbieri Mariano , Molcrette Bastien , Grandgirard Erwan , de Kort Marit AC , Meaburn Karen , Taylor Tiegh , Shchuka Virlana M , Kocanova Silvia , Monteiro Oliveira Guilherme , Mitchell Jennifer A , Soutoglou Evi , Lenstra Tineke L , Molina Nacho , Papantonis Argyris , Bystricky Kerstin , Sexton Tom
Published: April 2023

The spatiotemporal configuration of genes with distal regulatory elements, and the impact of chromatin mobility on transcription, remain unclear. Loop extrusion is an attractive model for bringing genetic elements together, but how this functionally interacts with transcription is also largely unknown. We combine live tracking of genomic loci and nascent transcripts with molecular dynamics simulations to assess the 4D arrangement of theSox2gene and its enhancer, in response to a battery of perturbations. We find that alterations in chromatin mobility, not promoter-enhancer distance, is more informative about transcriptional status. Active elements display more constrained mobility, consistent with confinement within specialized nuclear sites, and alterations in enhancer mobility distinguish poised from transcribing alleles. Strikingly, we find that whereas loop extrusion and transcription factor-mediated clustering contribute to promoter-enhancer proximity, they have antagonistic effects on chromatin dynamics. This provides an experimental framework for the underappreciated role of chromatin dynamics in genome regulation.
Introgression underlies phylogenetic uncertainty but not parallel plumage evolution in a recent songbird radiation
Authors: Rancilhac Loïs , Enbody Erik D. , Harris Rebecca , Saitoh Takema , Irestedt Martin , Liu Yang , Lei Fumin , Andersson Leif , Alström Per
Published: April 2023

Instances of parallel phenotypic evolution offer great opportunities to understand the evolutionary processes underlying phenotypic changes. However, confirming parallel phenotypic evolution and studying its causes requires a robust phylogenetic framework. One such example is the “black-and-white wagtails”, a group of five species in the songbird genusMotacilla: one species, the White Wagtail (M. alba), shows wide intra-specific plumage variation, while the four others form two pairs of very similar-looking species (African Pied WagtailM. aguimp+ Mekong WagtailM. samveasnaeand Japanese WagtailM. grandis+ White-browed WagtailM. maderaspatensis, respectively). However, the two species in each of these pairs were not recovered as sisters in previous phylogenetic inferences. Their relationships varied depending on the markers used, suggesting that gene tree heterogeneity might have hampered accurate phylogenetic inference. Here, we use whole genome resequencing data to explore the phylogenetic relationships within this group, with a special emphasis on characterizing the extent of gene tree heterogeneity and its underlying causes. We first used multispecies coalescent methods to generate a “complete evidence” phylogenetic hypothesis based on genome-wide variants, while accounting for incomplete lineage sorting and introgression. We then investigated the variation in phylogenetic signal across the genome, to quantify the extent of discordance across genomic regions, and test its underlying causes. We found that wagtail genomes are mosaics of regions supporting variable genealogies, because of ILS and inter-specific introgression. The most common topology across the genome, supportingM. albaandM. aguimpas sister species, appears to be influenced by ancient introgression. Additionally, we inferred another ancient introgression event, betweenM. albaandM. grandis. By combining results from multiple analyses, we propose a phylogenetic network for the black-and-white wagtails that confirms that similar phenotypes evolved in non-sister lineages, supporting parallel plumage evolution. Furthermore, the inferred reticulations do not connect species with similar plumage coloration, suggesting that introgression does not underlie parallel plumage evolution in this group. Our results demonstrate the importance of investigation of genome-wide patterns of gene tree heterogeneity to help understanding the mechanisms underlying phenotypic evolution.
Cdk/Cyclin activity helps set mitotic centrosome size by influencing the centrosome growth rate and growth period
Authors: Wong Siu-Shing , Wainman Alan , Saurya Saroj , Raff Jordan W.
Published: April 2023

Mitotic centrosomes assemble when centrioles recruit large amounts of pericentriolar material (PCM) around themselves in preparation for cell division. How the mitotic PCM grows to the correct size is unclear. InDrosophilasyncytial embryos, thousands of mitotic centrosomes assemble in a common cytoplasm as the embryo proceeds through 13 rounds of near-synchronous nuclear division. During nuclear cycles (NCs) 11-13 these divisions gradually slow, and we find that mitotic centrosomes respond by reciprocally slowing their growth rate and increasing their growth period so that they grow to a consistent size at each cycle. This size homeostasis is enforced, at least in part, by the Cdk/Cyclin cell cycle oscillator (CCO). Moderate levels of CCO activity appear to initially promote centrosome growth by stimulating Polo/PLK1 recruitment to centrosomes, while higher levels of activity subsequently inhibit centrosome growth by phosphorylating centrosome proteins to decrease their centrosomal recruitment and/or maintenance as the embryos enter mitosis. Thus, the CCO initially promotes, and subsequently restricts, mitotic centrosome growth to help ensure that centrosomes grow to a consistent size.
Functional Relations of CSLD2, CSLD3, and CSLD5 Proteins during Cell Wall Synthesis inArabidopsis
Authors: Yang Jiyuan , Sahu Abira , Adams Alexander , Yin Shuyao , Gu Fangwei , Mayes Heather B. , Nielsen Erik
Published: April 2023

Plant cell expansion is a dynamic process that is physically constrained by the deposition of new cell wall components. During tip growth, new cell wall materials are delivered at a restricted plasma membrane domain which results in a highly polarized expansion within that specified domain. Previous studies demonstrated that this process requires the activities of members of theCellulose Synthase-Like D (CSLD)subfamily of cell wall synthases. CSLD3 displays β-1,4 glucan synthase activity, but whether other members of CSLD subfamily share this conserved biochemical activity, and whether CSLD proteins form higher-order complexes to perform β-1,4 glucan synthase activities have not been determined. Here, we use genetic methods to demonstrate that CSLD2 and CSLD3 functions are interchangeable during root hair elongation and cell plate formation, while CSLD5 provides a unique and irreplaceable function in the formation of cell plates. Importantly, genetic analysis with inactivated versions of CSLD3 show that, unlike CESA proteins, CSLDs do not require the simultaneous presence of different isoforms to perform catalytic cell wall synthase activities.In vitrobiochemical activity experiments confirmed that CSLD2, CSLD3, and CSLD5 proteins displayed β-1,4 glucan synthases activities. Taken together, these results indicated that while all three vegetatively expressed CSLD proteins possess conserved β-1,4 glucan synthase activities, that CSLD5 has a more complicated and specialized role during cell plate formation.
Primary Ciliary Dyskinesia patient specific hiPSC-derived airway epithelium in Air Liquid Interface culture recapitulates disease specific phenotypesin vitro
Authors: von Schledorn Laura , Martín David Puertollano , Cleve Nicole , Zöllner Janina , Roth Doris , Staar Ben Ole , Hegermann Jan , Ringshausen Felix C. , Nawroth Janna , Martin Ulrich , Olmer Ruth
Published: April 2023

Primary ciliary dyskinesia (PCD) is a rare heterogenic genetic disorder associated with perturbed biogenesis or function of motile cilia. Motile cilia dysfunction results in diminished mucociliary clearance (MCC) of pathogens in the respiratory tract and chronic airway inflammation and infections successively causing progressive lung damage. Current approaches to treat PCD are symptomatic, only, indicating an urgent need for curative therapeutic options. Here, we developed anin vitromodel for PCD based on human induced pluripotent stem cell (hiPSC)-derived airway epithelium in Air-Liquid-Interface cultures. Applying transmission electron microscopy, immunofluorescence staining, ciliary beat frequency and mucociliary transport measurements, we could demonstrate that ciliated respiratory epithelia cells derived from two PCD patient specific hiPSC lines carrying mutations inDNAH5andNME5, respectively, recapitulate the respective diseased phenotype on a molecular, structural and functional level.
A high-throughput nematode sensory assay reveals an inhibitory effect of ivermectin on parasite gustation
Authors: Nunn Leonardo R. , Juang Terry D. , Beebe David J. , Wheeler Nicolas J. , Zamanian Mostafa
Published: April 2023

Sensory pathways first elucidated inCaenorhabditis elegansare conserved across free-living and parasitic nematodes, even though each species responds to a diverse array of compounds. Most nematode sensory assays are performed by tallying observations of worm behavior on two-dimensional planes using agarose plates. These assays have been successful in the study of volatile sensation but are poorly suited for investigation of water-soluble gustation or parasitic nematodes without a free-living stage. In contrast, gustatory assays tend to be tedious, often limited to the manipulation of a single individual at a time. We have designed a nematode sensory assay using a microfluidics device that allows for the study of gustation in a 96-well, three-dimensional environment. This device is suited for free-living worms and parasitic worms that spend their lives in an aqueous environment, and we have used it to show that ivermectin inhibits the gustatory ability of vector-borne parasitic nematodes.
Illuminating the charged leptons in the proton
Authors: Gonçalves Victor P. , Martins Daniel E.
Published: April 2023

The description of the structure of proton is fundamental in order to describe the standard model processes at the LHC as well as for the searching of new physics. Quantum fluctuations imply the presence of photons and leptons inside the proton, which admit a parton distribution function (PDF). Although the lepton PDFs are expected to be small, its presence opens new production mechanisms. In order to explore the lepton-induced processes at the LHC, a precise determination of the leptonic content of the proton is needed. In this paper we propose to constrain the content of charged leptons inside the proton through the study of the QED Compton scattering in ultraperipheral proton-nucleus collisions at the LHC. We estimate the total cross sections and associated distributions considering different models for the lepton PDFs and distinct lepton flavors. We demonstrate that a future experimental analysis of this process is feasible and that it can be used to constrain the content of electrons, muons, and taus inside the proton.

Published by the American Physical Society
2023
The crystal structure of the killer fibre erionite from Tuzköy (Cappadocia, Turkey)
Authors: Giacobbe Carlotta , Moliterni Anna , Di Giuseppe Dario , Malferrari Daniele , Wright Jonathan P. , Mattioli Michele , Raneri Simona , Giannini Cinzia , Fornasini Laura , Mugnaioli Enrico , Ballirano Paolo , Gualtieri Alessandro F.
Published: April 2023

Erionite is a non-asbestos fibrous zeolite classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen and is considered today similar to or even more carcinogenic than the six regulated asbestos minerals. Exposure to fibrous erionite has been unequivocally linked to cases of malignant mesothelioma (MM) and this killer fibre is assumed to be directly responsible for more than 50% of all deaths in the population of the villages of Karain and Tuzköy in central Anatolia (Turkey). Erionite usually occurs in bundles of thin fibres and very rarely as single acicular or needle-like fibres. For this reason, a crystal structure of this fibre has not been attempted to date although an accurate characterization of its crystal structure is of paramount importance for our understanding of the toxicity and carcinogenicity. In this work, we report on a combined approach of microscopic (SEM, TEM, electron diffraction), spectroscopic (micro-Raman) and chemical techniques with synchrotron nano-single-crystal diffraction that allowed us to obtain the first reliable ab initio crystal structure of this killer zeolite. The refined structure showed regular T—O distances (in the range 1.61–1.65 Å) and extra-framework content in line with the chemical formula (K2.63Ca1.57Mg0.76Na0.13Ba0.01)[Si28.62Al7.35]O72·28.3H2O. The synchrotron nano-diffraction data combined with three-dimensional electron diffraction (3DED) allowed us to unequivocally rule out the presence of offretite. These results are of paramount importance for understanding the mechanisms by which erionite induces toxic damage and for confirming the physical similarities with asbestos fibres.
Surface-modified cerium oxide as a corrosion inhibitor to enhance the performance of epoxy coatings
Authors: Dong Yinxia , Zhang Yingjun , Cui Xue-Jun , Li Mingtian , Xie Chun , Pan Zhongwen
Published: April 2023

Purpose

The study aims to investigate the anticorrosion performance of epoxy coatings using modified cerium oxide (CeO2) by terephthalic acid (CeO2-t) and fumaric acid (CeO2-f) as corrosion inhibitors.

Design/methodology/approach

The chemical state of CeO2-t, and CeO2-f were analyzed by infrared radiation (IR) and X-ray diffraction (XRD). The effect of different inhibitors on the coating properties was analyzed by neutral salt spray tests (NSST) and electrochemical impedance spectroscopy (EIS).

Findings

The results of IR and XRD illustrate that the modification of CeO2 was successful, and fumaric acid underwent a ring-opening reaction with epoxy resin (EP) in the coatings. The results of NSST and EIS showed that the coatings containing CeO2-f exhibited the best anticorrosion performance.

Originality/value

CeO2 is an effective inhibitor of the organic coatings. When surface modified, it is chemically bonded to EP, enhancing the anticorrosion performance of EP.
Online food delivery habits and its environmental impact during the COVID-19 pandemic: an Italian and Polish study
Authors: Varese Erica , Cesarani Maria Chiara , Kabaja Bartłomiej , Sołtysik Mariusz , Wojnarowska Magdalena
Published: April 2023

Purpose

The purpose of this paper is to investigate, through a quantitative research, the impact of the COVID-19 pandemic on online food delivery in Italy and Poland, as well as to ascertain whether or not, under a consumer perspective, respondents consider such method as impacting on the environment and on food waste.

Design/methodology/approach

An empirical survey of consumers at Italian and Polish Universities was conducted using the online survey computer-assisted web interview (CAWI) method.

Findings

Results reveal that the COVID-19 pandemic has modified consumer habits in both Italy and Poland, though the researched sample does not have full knowledge of these changes. Moreover, the study has proved once again that online food delivery may impact negatively on the environment and the food waste issue.

Originality/value

This paper fills a gap in literature since, by the authors' knowledge, it is the first quantitative study analysing Italian and Polish young consumers as to online food delivery habits and their approach to sustainability aspects of this purchasing method.
Does workplace toxicity undermine psychological capital (PsyCap) of the employees? Exploring the moderating role of gratitude
Authors: Mahipalan Manju , Garg Naval
Published: April 2023

Purpose

This paper aims to examine the relationship between workplace toxicity and psychological capital (PsyCap). It also investigates the moderating role of gratitude in the toxicity–PsyCap link.

Design/methodology/approach

The study is based on explorative-cum-descriptive research design. The sample comprises 411 employees engaged in banking, insurance, IT, automobile and oil and gas companies. The collected data is explored for reliability, validity, multicollinearity and common method variance estimates. Also, the relationship between workplace toxicity and PsyCap and the moderating effect of gratitude are examined using structural equation modelling.

Findings

The findings report a negative association between toxicity and PsyCap. Also, the study concludes a significant moderating effect of gratitude. The study recommends the institutionalisation of a gratitude-based organisation to reduce the impact of workplace bullying and uncivil behaviour.

Originality/value

The study is based on primary data and one of the few studies that explore psychological capital as a dependent variable, which is influenced by toxic behaviours at work.
Optimal strategies for nanostores under competition in community group buying
Authors: Shu Lingli , Li Xiaoyan , Liang Xuedong
Published: April 2023

Purpose

For nanostores, striving to become the community group-buying leader is gaining prominence. This paper aims to construct Hotelling linear models to investigate whether nanostores should be registered as leaders and their decisions in a competitive environment.

Design/methodology/approach

This paper constructs three Hotelling linear models: neither nanostore registers as community leader, only one nanostore registers as community leader and both nanostores register as community leader. The competitive operation strategies of two general nanostores under three scenarios are solved.

Findings

The study finds that nanostores without a cost advantage may benefit from being the first leader. The nanostore's preferred decisions depend on the investment cost parameters of its own and competitors which may lead to market share competition. Furthermore, consumers' sensitivity to community group-buying service has a negative effect on nanostores' profit.

Originality/value

The study is one of the few to consider the competition between community leaders. Besides, the study considers that the utilities functions of consumers are concurrently impacted by the service decisions, along with the price in different nanostores. It can provide nanostores useful implications in the dynamic industry.
Library book recommendation with CNN-FM deep learning approach
Authors: Shi Xiaohua , Hao Chen , Yue Ding , Lu Hongtao
Published: April 2023

Purpose

Traditional library book recommendation methods are mainly based on association rules and user profiles. They may help to learn about students' interest in different types of books, e.g., students majoring in science and engineering tend to pay more attention to computer books. Nevertheless, most of them still need to identify users' interests accurately. To solve the problem, the authors propose a novel embedding-driven model called InFo, which refers to users' intrinsic interests and academic preferences to provide personalized library book recommendations.

Design/methodology/approach

The authors analyze the characteristics and challenges in real library book recommendations and then propose a method considering feature interactions. Specifically, the authors leverage the attention unit to extract students' preferences for different categories of books from their borrowing history, after which we feed the unit into the Factorization Machine with other context-aware features to learn students' hybrid interests. The authors employ a convolution neural network to extract high-order correlations among feature maps which are obtained by the outer product between feature embeddings.

Findings

The authors evaluate the model by conducting experiments on a real-world dataset in one university. The results show that the model outperforms other state-of-the-art methods in terms of two metrics called Recall and NDCG.

Research limitations/implications

It requires a specific data size to prevent overfitting during model training, and the proposed method may face the user/item cold-start challenge.

Practical implications

The embedding-driven book recommendation model could be applied in real libraries to provide valuable recommendations based on readers' preferences.

Originality/value

The proposed method is a practical embedding-driven model that accurately captures diverse user preferences.