bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of hinged wings in strong upward gusts
Authors: Stevenson Jonathan P. J. , Cheney Jorn A. , Usherwood James R. , Bomphrey Richard J. , Windsor Shane P.
Published: August 2022

A bird’s wings are articulated to its body via highly mobile shoulder joints. The wings possess an impressive range of motion, which allows for movements that can modulate the production of aerodynamic load in flight. This is crucial for stability and control—particularly in gusty or turbulent environments. In this study, we develop a dynamics model to examine how a bird-scale gliding aircraft can use wing-root hinges (analogous to avian shoulder joints) to reject the initial impact of a strong upward gust. Our idea requires that the spanwise centre of pressure and the centre of percussion of the hinging wing start, and stay, in good initial alignment (the centre of percussion here is related to the idea of a ‘sweet spot’ on a bat, as in cricket or baseball). We propose a method for achieving this rejection passively, for which the essential ingredients are: (i) well-considered lift and mass distributions; (ii) constant-torque hinges; and (iii) a wing whose sections stall softly. When configured correctly, the gusted wings will first pivot on their hinges without disturbing the fuselage of the aircraft, affording time for other corrective actions to engage. We expect this system to enhance the control of aircraft that fly in gusty conditions.
Multiscale Analysis of Pangenome Enables Improved Representation of Genomic Diversity For Repetitive And Clinically Relevant Genes
Authors: Chin Chen-Shan , Behera Sairam , Khalak Asif , Sedlazeck Fritz J , Wagner Justin , Zook Justin M.
Published: August 2022

The advancements in sequencing technologies and assembly methods enable the regular production of high-quality genome assemblies characterizing complex regions. However, challenges remain in efficiently interpreting variations at various scales, from smaller tandem repeats to megabase re-arrangements, across many human genomes. We present a pangenome research toolkit enabling analyses of complex pangenome variations at multiple scales. A graph decomposition method is developed for interpreting such variations. Surveying a set of 395 challenging and medically important genes in pangenome provides quantitative insights into repetitiveness and diversity that could impact the accuracy of variant calls. We apply the graph decomposition methods to the Y-chromosome gene, DAZ1/DAZ2/DAZ3/DAZ4, of which structural variants have been linked to male infertility, and X-chromosome genes OPN1LW and OPN1MW linked to eye disorders, highlighting the power of PGR-TK and pangenomics to resolve complex variation in regions of the genome that were previously too complex to analyze across many haplotypes.
Phanta: Phage-inclusive profiling of human gut metagenomes
Authors: Pinto Yishay , Chakraborty Meenakshi , Jain Navami , Bhatt Ami S
Published: August 2022

The human gut microbiome is a diverse ecosystem that encompasses multiple domains of life and plays a vital role in human health. Due to technical limitations, most microbiome studies have focused on gut prokaryotes, overlooking bacteriophages and other gut viruses. The most common method to profile viruses is to assemble shotgun metagenomic reads - often from virus-enriched samples - and identify viral genomes de novo. While valuable, this resource-intensive and reference-independent method has limited sensitivity. To overcome these drawbacks, we developed Phanta, which profiles human gut metagenomes in a virus-inclusive manner directly from short reads utilizing recently published catalogs of gut viral genomes. Phanta incorporates k-mer based classification tools and was developed with virus-specific properties in mind. Specifically, it includes optimizations considering viruses’ small genome size, sequence homology with prokaryotes, and interactions with other members of the gut microbial community. Based on simulations, the workflow is fast and accurate with respect to both prokaryotes and viruses, minimizing false positive species identification using a novel genome coverage-based strategy. When applied to metagenomes from healthy adults, Phanta identified ~200 viral species per sample, ~5x more than the standard assembly-based methods. Notably, we observed a 2:1 ratio between gut viruses and bacteria, with higher interindividual variability of the gut virome compared to the gut bacteriome. Phanta performs equally well on bulk vs. virus-enriched metagenomes, making it possible to study prokaryotes and viruses in a single experiment, with a single analysis. Phanta can tandemly profile gut viruses and prokaryotes in existing and novel datasets, and can therefore identify cross-domain interactions with likely relevance to human health. We expect that Phanta will reduce the barrier to virus-inclusive studies of the human gut microbiome, thus making it standard practice.
Alveolar Repair Following Lipopolysaccharide-induced Injury Requires Cell-Extracellular Matrix Interactions
Authors: Sucre Jennifer M.S. , Bock Fabian , Negretti Nicholas M. , Benjamin John T. , Gulleman Peter M. , Dong Xinyu , Ferguson Kimberly T. , Jetter Christopher S. , Han Wei , Liu Yang , Kook Seunghyi , Gokey Jason J. , Guttentag Susan H. , Kropski Jonathan A. , Blackwell Timothy S. , Zent Roy , Plosa Erin J.
Published: August 2022

During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat type 1 alveolar epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severity of injury. To test if β1-containing integrins are required during repair following acute injury, we administeredE. colilipopolysaccharide (LPS) by intratracheal injection to mice with a post-developmental deletion of β1 integrin in AT2 cells. While control mice recovered from LPS injury without structural abnormalities, β1-deficient mice had more severe inflammation and developed emphysema. In addition, recovering alveoli were repopulated with an abundance of rounded epithelial cells co-expressing type 2, type 1, and mixed intermediate cell state markers, with few mature type 1 cells. β1-deficient AT2 cells showed persistently increased proliferation after injury, which was blocked by inhibiting NF-κB activation in these cells. Lineage tracing experiments revealed that β1-deficient AT2 cells failed to differentiate into mature type 1 alveolar epithelial cells. Together, these findings demonstrate that functional alveolar repair after injury with terminal alveolar epithelial differentiation requires β1-containing integrins.
Severity Predictors of COVID-19 in SARS-CoV-2 Variant, Delta and Omicron Period; Single Center Study
Authors: Ogawa Fumihiro , Oi Yasufumi , Honzawa Hiroshi , Misawa Naho , Takeda Tomoaki , Kikuchi Yuusuke , Fukui Ryosuke , Tanaka Katsushi , Kano Daiki , Kato Hideaki , Abe Takeru , Takeuchi Ichiro
Published: August 2022

Background

The outcomes of coronavirus disease 2019 (COVID-19) treatment have improved due to vaccination and the establishment of better treatment regimens. However, the emergence of variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, and the corresponding changes in the characteristics of the disease present new challenges in patient management. This study aimed to analyze predictors of COVID-19 severity caused by the delta and omicron variants of SARS-CoV-2.

Methods

We retrospectively analyzed the data of patients who were admitted for COVID-19 at Yokohama City University Hospital from August 2021 to March 2022.

Results

A total of 141 patients were included in this study. Of these, 91 had moderate COVID-19, whereas 50 had severe COVID-19. There were significant differences in sex, vaccination status, dyspnea, sore throat symptoms, and body mass index (BMI) (p <0.0001, p <0.001, p <0.001, p=0.02, p< 0.0001, respectively) between the moderate and severe COVID-19 groups. Regarding comorbidities, smoking habit and renal dysfunction were significantly different between the two groups (p=0.007 and p=0.01, respectively). Regarding laboratory data, only LDH level on the first day of hospitalization was significantly different between the two groups (p<0.001). Multiple logistic regression analysis revealed that time from the onset of COVID-19 to hospitalization, BMI, smoking habit, and LDH level were significantly different between the two groups (p<0.03, p=0.039, p=0.008, p<0.001, respectively). The cut-off value for the time from onset of COVID-19 to hospitalization was four days (sensitivity, 0.73; specificity, 0.70).

Conclusions

Time from the onset of COVID-19 to hospitalization is the most important factor in the prevention of the aggravation of COVID-19 caused by the delta and omicron SARS-CoV-2 variants. Appropriate medical management within four days after the onset of COVID-19 is essential for preventing the progression of COVID-19, especially in patients with smoking habits.
Alcanivorax borkumensisBiofilms Enhance Oil Degradation By Interfacial Tubulation
Authors: Prasad M. , Obana N. , Lin S.-Z. , Sakai K. , Blanch-Mercader C. , Prost J. , Nomura N. , Rupprecht J.-F. , Fattaccioli J. , Utada A. S.
Published: August 2022

Alcanivorax borkumensisare prominent actors in oil spill bioremediation; however, the interfacial dynamics of their biofilms and its role in oil degradation remain unclear. Longitudinal tracking of biofilm-covered oil microdroplets using microfluidics reveals a spontaneous morphological transition from a thick biofilm phenotype to a thin dendritic phenotype optimized for high oil consumption rates. We show experimentally that biofilm dendrites emerge from aster-like nematic defects in the thin biofilms. We develop a theoretical model that elucidates the transition between phenotypes, linking tubulation to decreased interfacial tension and increased cell hydrophobicity, which we verify experimentally. We demonstrate positional control over the nematic defects on the droplets using microfluidics, causing the biofilm to dimple the droplets. Our results reveal howA. borkumensisbiofilms utilize topological defects to increase oil access to achieve superior oil consumption rates, which may be a general strategy in oil-consuming bacteria.

ONE SENTENCE SUMMARY

A. borkumensisadapt their interfacial properties over time to evolve their biofilm phenotype and increase their oil consumption
Beyond variance: simple random distributions are not a good proxy for intraspecific variability in systems with environmental structure
Authors: Girard-Tercieux Camille , Vieilledent Ghislain , Clark Adam , Clark James S. , Courbaud Benoit , Fortunel Claire , Kunstler Georges , Pélissier Raphaël , Rüger Nadja , Maréchaux Isabelle
Published: August 2022

The role of intraspecific variability (IV) in shaping community dynamics and species coexistence has been intensively discussed over the past decade and modelling studies have played an important role in that respect. However, these studies often implicitly assume that IV can be represented by independent random draws around speciesspecific mean parameters. This major assumption has largely remained undiscussed, although a great part of observed IV is structured in space or time, in particular when environmental dimensions that influence individual performance are imperfectly characterised or unobserved in the field. To test the impact of this strong assumption on the outcome of community dynamics models, we designed a simulation experiment where we varied the level of knowledge of the environment in virtual communities, resulting in different relative importance of explainedvsunexplained spatial individual variation in performance. We used a community dynamics simulator to generate communities where the unexplained individual variation is, or is not, added as an unstructured random noise. Communities simulated with unstructured IV never reached the community diversity and composition of those where all the variation was explained and structured (perfect knowledge model). This highlights that incorporating unstructured IV (i.e. a random noise) to account for unexplained (but structured) variation can lead to incorrect simulations of community dynamics. In addition, the effects of unstructured IV on community diversity and composition depended on the relative importance of structuredvsunstructured IV,i.e. on the level of knowledge of the environment, which may partly explain the contrasting results of previous studies on the effect of IV on species coexistence. In particular, the effect of unstructured IV on community diversity was positive when the proportion of structured IVvsunstructured IV in the model was low, but negative when this proportion was high. This is because unstructured random noise can either limit the competitive exclusion of inferior competitors in low dimensions or destabilise tight niche partitioning in high dimension. Our study suggests that it is crucial to account for the sources and structure of observed IV in real communities to better understand its effect on community assembly and properly include it in community dynamics models.
A spatialised agent-based model of NOTCH signalling pathway in Endothelial Cells predicts emergent heterogeneity due to continual dynamic phenotypic adjustments
Authors: Chesnais Francois , Sego Timothy J , Engstler Elena , Battilocchi Matteo , Danovi Davide , Glazier James A , Veschini Lorenzo
Published: August 2022

Vascular Endothelial Cells (EC) plasticity is key to homeostasis and its disruption is a hallmark of diseases such as cancer, atherosclerosis, and diabetes. The EC lineage has evolved to address in parallel sensor and actuator functions. This ability is reflected in remarkable phenotypical heterogeneity of EC across different tissues, within the same tissue, and within the same vascular bed as demonstrated by single cell image analysis and transcriptomics studies. However, how the molecular signalling dynamics in EC could generate and maintain such heterogeneity in different contexts is still largely unexplored. Recently we reported that confluent EC have spatially heterogeneous NOTCH signalling pathway (NSP) levels in vitro as confirmed from analysis of available OMICS databases. Here, we show that spatial heterogeneity of NSP levels is a feature of aortic murine endothelia in vivo and recapitulated by human EC in culture despite absence of signalling from mural cells. We study lateral induction and inhibition, cis-interactions and signalling, and target genes autoregulation in NSP. Using mathematical models and experimental observations we report that NSP dynamics can generate stable, periodic, and asynchronous oscillations of the NSP target HES1. Importantly, we observe that cell contact dependent NSP signal oscillations is the most likely parsimonious mechanistic hypothesis justifying observed spatial heterogeneity in endothelia. We propose that NSP is sufficient to enable individual EC in monolayers to acquire different phenotypes dynamically explaining robustness of quiescent endothelia in performing parallel functions.
Factors associated with peri-neonatal mortality in Sao Tome & Principe: a prospective cohort study
Authors: Vasconcelos Alexandra , Sousa Swasilanne , Bandeira Nelson , Alves Marta , Papoila Ana Luísa , Pereira Filomena , Machado Maria Céu
Published: August 2022

Background

Neonatal mortality reduction is a global goal but its factors in high-burden nations vary and are poorly understood. This study was conducted to identify the factors affecting peri- neonatal mortality in Sao Tome & Principe (STP), one of the smallest African countries.

Methods

Institution-based prospective cohort study conducted at Hospital Dr. Ayres Menezes. Maternal-neonate dyads enrolled were followed up after the 28thday of life (n=194) for identification of neonatal death-outcome (n=22) and alive-outcome groups (n=172). Data were collected from pregnancy cards, hospital records and face-to-face interviews. After the 28thday of birth, a phone call was made to evaluate the newborn’s health status. A logistic regression model was used to identify the relevant factors associated with mortality, a p value <0.05 was considered statistically significant.

Results

The mean gestational age of the death-outcome and alive-outcome groups was 36 (SD=4.8) and 39 (SD=1.4) weeks, respectively. Death-outcome group (n=22) included sixteen stillbirths, four early and two late neonatal deaths. High-risk pregnancy score [cOR 2.91, 95%CI:1.18-7.22], meconium-stained fluid [cOR 4.38, 95%CI:1.74–10.98], prolonged rupture of membranes [cOR 4.84, 95%CI:1.47–15.93], transfer from another unit [cOR 6.08, 95%CI:1.95–18.90], and instrumental vaginal delivery [cOR 8.90, 95%CI:1.68–47.21], were factors significantly associated with mortality. The odds of experiencing death were higher for newborns with infectious risk, IUGR, resuscitation maneuvers, fetal distress at birth, birth asphyxia, and unit care admission. Female newborn [cOR 0.37, 95%CI:0.14-1.00] and birth weight of more than 2500 g [cOR 0.017, 95%CI:0.002-0.162] were found to be protective factors. In the multivariable model, meconium-stained fluid was significantly associated with death outcome.

Conclusion

Factors such as having a high-risk pregnancy score, meconium-stained amniotic fluid, prolonged rupture of membranes, being transferred from another unit, and an instrumental- assisted vaginal delivery increased 4– to 9–fold the risk of stillbirth and neonatal death. Of the factors associated with peri-neonatal mortality in this study, avoiding health-worker- related factors associated with delays in prompt intrapartum care is a key strategy to implement in Sao Tome & Principe.
A Comprehensive Survey of C. elegans Argonaute Proteins Reveals Organism-wide Gene Regulatory Networks and Functions
Authors: Seroussi Uri , Lugowski Andrew , Wadi Lina , Lao Robert X. , Willis Alexandra R. , Zhao Winnie , Sundby Adam E. , Charlesworth Amanda G. , Reinke Aaron W. , Claycomb Julie M.
Published: August 2022

Argonaute (AGO) proteins associate with small RNAs to direct their effector function on complementary transcripts. The nematode C. elegans contains an expanded family of 19 functional AGO proteins, many of which have not been fully characterized. In this work we systematically analyzed every C. elegans AGO, using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG tags. We have characterized the expression patterns of each AGO throughout development, identified small RNA binding complements, and determined the effects of ago loss on small RNA populations and developmental phenotypes. Our analysis indicates stratification of subsets of AGOs into distinct regulatory modules, and integration of our data led us to uncover novel stress-induced fertility and pathogen response phenotypes due to ago loss.
Dynamic allosteric networks drive adenosine A1receptor activation and G-protein coupling
Authors: Maria-Solano Miguel A. , Choi Sun
Published: August 2022

G-protein coupled receptors (GPCRs) present specific activation pathways and signaling among receptor subtypes. Hence, an extensive knowledge of the structural dynamics of the receptor is critical for the development of therapeutics. Here, we target the adenosine A1receptor (A1R), for which a negligible number of drugs have been approved. We combine molecular dynamics simulations, enhanced sampling techniques, network theory and pocket detection to decipher the activation pathway of A1R, decode the allosteric networks and identify transient pockets. The A1R activation pathway reveal hidden intermediate and pre-active states together with the inactive and fully-active states observed experimentally. The protein energy networks computed throughout these conformational states successfully unravel the extra and intracellular allosteric centers and the communication pathways that couples them. We observe that the allosteric networks are dynamic, being increased along activation and fine-tuned in presence of the trimeric G-proteins. Overlap of transient pockets and energy networks uncover how the allosteric coupling between pockets and distinct functional regions of the receptor is altered along activation. By an in-depth analysis of the bridge between activation pathway, energy networks and transient pockets, we provide a further understanding of A1R. This information can be useful to ease the design of allosteric modulators for A1R.
UNC-45 assisted myosin folding depends on a conserved FX3HY motif implicated in Freeman Sheldon Syndrome
Authors: Vogel Antonia , Arnese Renato , Gudino Carrillo Ricardo M. , Sehr Daria , Bylicki Andrzej , Meinhart Anton , Clausen Tim
Published: August 2022

Myosin motors are critical for diverse motility functions ranging from cytokinesis and endocytosis to muscle contraction. The UNC-45 chaperone controls myosin function mediating the folding, assembly, and degradation of the muscle protein. Here, we analyze the molecular mechanism of UNC-45 as a hub in myosin quality control. We show that UNC-45 forms discrete complexes with folded and unfolded myosin, forwarding them to downstream chaperones and E3 ligases. Structural analysis of a minimal chaperone:substrate complex reveals that UNC-45 binds to a conserved FX3HY motif in the myosin motor domain. Disrupting the observed interface by mutagenesis prevents myosin maturation leading to protein aggregation in vivo. We also show that a mutation in the FX3HY motif linked to the Freeman Sheldon Syndrome impairs UNC-45 assisted folding, reducing the level of functional myosin. These findings demonstrate that a faulty myosin quality control is a critical yet unexplored cause of human myopathies.
Asymmetry and ion selectivity properties of bacterial channel NaK mutants mimicking ionotropic glutamate receptors
Authors: Minniberger Sonja , Abdolvand Saeid , Braunbeck Sebastian , Sun Han , Plested Andrew J.R.
Published: August 2022

Ionotropic glutamate receptors are ligand-gated cation channels that play essential roles in the excitatory synaptic transmission throughout the central nervous system. A number of open-pore structures of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid (AMPA)-type glutamate receptors became recently available by cryo-electron microscopy (cryo-EM). These structures provide valuable insights into the conformation of the selectivity filter (SF), the part of the ion channel that determines the ion selectivity. Nonetheless, due to the moderate resolution of the cryo-EM structures, detailed information such as ion occupancy of monovalent and divalent cations as well as exact displacement of the side-chains in the SF is still missing. Here, in order to resolve high-resolution crystal structures of the AMPA SF in its open-state, we incorporated the partial SF sequence of the AMPA receptor into the bacterial tetrameric cation channel NaK, which served as a structural scaffold. We determined a series of X-ray structures of NaK-CDI, NaK-SDI and NaK-SELM mutants at 1.42-2.10 Å resolution, showing distinct ion occupation of different monovalent cations. Molecular dynamics (MD) simulations of NaK-CDI indicated the channel to be conductive to monovalent cations, which agrees well with our electrophysiology recordings. Moreover, unique structural asymmetry of the SF was revealed by the X-ray structures and MD simulations, implying its importance in ion non-selectivity of tetrameric cation channels.
Analysis of genetic relatedness between gastric and oral H. pylori in patients with early gastric cancer using multilocus sequence typing
Authors: Nagata Ryoko , Sato Hiroki , Takenaka Shoji , Yokoyama Junji , Terai Shuji , Mimuro Hitomi , Noiri Yuichiro
Published: August 2022

Although oral cavity is the second most colonized site after the stomach, the association between gastric and oral Helicobacter pylori remains unclear. This study aimed to compare the genetic relatedness between gastric and oral H. pylori in Japanese patients with early gastric cancer by multilocus sequence typing (MLST) analysis using seven housekeeping genes. Gastric biopsy specimens and oral samples, including saliva, supragingival dental biofilm, and superficial layers of the tongue, were collected from 21 patients positive for H. pylori by a fecal antigen test. The number of H. pylori allelic profiles of seven loci obtained from oral and gastric samples ranged from zero to seven since the yield of DNA was small even when the nested PCR was performed. The alleles of seven loci from both collection sites were determined from only one patient, and two out of seven alleles matched between oral and gastric samples. MLST analysis revealed that only one sample had a matching oral and gastric H. pylori genotype, suggesting that different genotypes of H. pylori inhabit the oral cavity and gastric mucosa. The phylogenetic analysis showed that oral H. pylori in two patients was markedly similar to gastric H. pylori, implying that the the origins of two strains may be the same, and the stomach and the oral cavity may be infected at the same time. In brief, although different genotypes of H. pylori exist in the oral cavity independently of H. pylori present in the stomach, there are rare cases in which the same H. pylori is present in the stomach and the oral cavity. It is necessary to establish a culture method for oral H. pylori for elucidating whether the oral cavity will act as the source of the gastric infection, as our analysis was based on a limited number of allele sequences.

Author summary

Hericobacter pylori is a clinically important pathogen that causes chronic gastritis and peptic ulcers, which are associated with gastric carcinoma. Oral H. pylori DNA has also been detected in a range of oral specimens, including saliva, supra- or sub-gingival biofilm, dentin caries, dental pulp, infected root canal, and coating of the tongue. Thus, researchers speculate that the main route of transmission of gastric H. pylori infections is via the oral cavity, however, there is inadequate evidence to support this suggestion. This study aimed to investigate if the oral and gastric H. pylori have the same origin using multilocus sequence typing. The results of this study provided some insight into the role of oral cavity as the source of H. pylori infections in stomach.
Single-molecule tracking of Nanog and Oct4 in mouse embryonic stem cells
Authors: Okamoto Kazuko , Fujita Hideaki , Okada Yasushi , Shinkai Soya , Onami Shuichi , Abe Kuniya , Fujimoto Kenta , Watanabe Tomonobu M
Published: August 2022

Nanog and Oct4 are core transcription factors in a gene regulatory network that regulate hundreds of target genes for pluripotency maintenance in mouse embryonic stem cells. To understand their function as a gatekeeper or a pioneer factor at the molecular scale, we quantified the residence time on target loci, fluctuation at the loci, and interaction clustering by visualizing single molecules of Nanog and Oct4 in a living nucleus during the pluripotency loss. Interestingly, Nanog interacted longer with its target loci in the lower Nanog expression state or at the onset of differentiation, indicating the possibility of a new feedback mechanism to maintain Nanog expression. The interaction time of Nanog and Oct4 corresponded to their fluctuation and interaction clustering, which depended on their expression or differentiation state, respectively. The DNA viscoelasticity near the Oct4 target locus remained flexible during the differentiation, reflecting its role as a pioneer factor. Based on these results, we propose a new feedback mechanism for pluripotency maintenance in which Nanog function is prolonged, corresponding to chromatin condensation, and Oct4 reopens the condensation.
Cotranslational folding of human growth hormone in vitro and in Escherichia coli
Authors: Mermans Daphne , Nicolaus Felix , Baygin Aysel , von Heijne Gunnar
Published: August 2022

Human growth hormone (hGH) is a four-helix bundle protein of considerable pharmacological interest. Recombinant hGH is produced in bacteria, yet little is known about its folding during expression in E. coli. We have studied the cotranslational folding of hGH using Force Profile Analysis (FPA), both during in vitro translation in the absence and presence of the chaperone trigger factor (TF), and when expressed in E. coli. We find that the main folding transition starts before hGH is completely released from the ribosome, and that it can interact with TF and possibly other chaperones.
Purine-rich RNA sequences in the 5’UTR site-specifically regulate eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation
Authors: Schmidt Tobias , Dabrowska Adrianna , Waldron Joseph A. , Hodge Kelly , Koulouras Grigorios , Gabrielsen Mads , Munro June , Tack David C. , Harris Gemma , McGhee Ewan , Scott David , Carlin Leo M. , Huang Danny , Le Quesne John , Zanivan Sara , Wilczynska Ania , Bushell Martin
Published: August 2022

Oncogenic translational programmes underpin cancer development and are often driven by dysregulation of oncogenic signalling pathways that converge on the eukaryotic translation initiation (eIF) 4F complex. Altered eIF4F activity promotes translation of oncogene mRNAs that typically contain highly structured 5’UTRs rendering their translation strongly dependent on RNA unwinding by the DEAD-box helicase eIF4A1 subunit of the eIF4F complex. While eIF4A1-dependent mRNAs have been widely investigated, it is still unclear how highly structured mRNAs recruit and activate eIF4A1 unwinding specifically to facilitate their preferential translation.

Here, we show that RNA sequence motifs regulate eIF4A1 unwinding activity in cells. Our data demonstrate that eIF4A1-dependent mRNAs contain AG-rich motifs within their 5’UTR which recruit and stimulate eIF4A1 unwinding of localised RNA structure to facilitate mRNA translation. This mode of eIF4A1 regulation is used by mRNAs encoding components of mTORC-signalling and cell cycle progression and renders these mRNAs particularly sensitive to eIF4A1-inhibition. Mechanistically, we show that binding of eIF4A1 to AG-rich sequences leads to multimerization of eIF4A1 with eIF4A1 subunits performing distinct enzymatic activities. Our structural data suggest that RNA-binding of multimeric eIF4A1 induces conformational changes in the RNA substrate resulting in an optimal positioning of eIF4A1 proximal to the RNA duplex region that supports efficient unwinding.

Hence, we conclude a model in which mRNAs utilise AG-rich sequences to specifically recruit eIF4A1, enabling assembly of the helicase-active multimeric eIF4A1 complex, and positioning these complexes proximal to stable localised RNA structure allowing ribosomal subunit scanning.
Static stability and swim bladder volume in the bluegill sunfish Lepomis macrochirus
Authors: Fath Michael , Nguyen Stacy , Donahue Joan , McMenamin Sarah , Tytell Eric
Published: August 2022

The static stability of a fish in the water is determined by the relative locations of its center of mass and center of buoyancy. These locations may not be constant, but may depend on the volume of the swim bladder. Changes in swim bladder volume affect both the distribution of mass and the overall volume of the fish, thus affecting the location of the center of mass and center of buoyancy, respectively. To determine the static stability and to examine the influence of the swim bladder on static stability, we used micro-computed tomography to estimate the locations of the center of mass and center of buoyancy in bluegill sunfish (Lepomis macrochrius). In fish oriented head up in the scanner, we found that the center of buoyancy is located 0.441 body lengths from the snout and 0.19 body lengths above the ventral surface of the pelvic girdle, and that the center of mass is 0.0012 BL posterior to and 0.00045 BL ventral to the center of buoyancy. Swim bladders from our specimens ranged in size from 1.9% to 7.6% total body volume, and we found no correlation between swim bladder volume and the distance between the center of mass and center of buoyancy. However, in fish scanned in a head-down orientation, the center of mass is anterior and dorsal to the center of buoyancy—the opposite configuration of that found in fish oriented head up. This change in center of mass and center of buoyancy seems to be caused by changes in the location of the swim bladder in the body: the centroid of the swim bladder is located more posteriorly in fish oriented head-down. The air in the bladder “rises” while heavier tissues “sink,” driving a change in tissue distribution and changing the location of the center of mass relative to the center of buoyancy. We conclude that while static stability does not change with swim bladder volume, pitch angle could have a marked effect on static stability.
A replicon RNA vaccine induces durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned
Authors: O’Connor Megan A. , Hawman David W. , Meade-White Kimberly , Leventhal Shanna , Song Wenjun , Randall Samantha , Archer Jacob , Lewis Thomas B. , Brown Brieann , Iwayama Naoto , Ahrens Chul , Garrison William , Wangari Solomon , Guerriero Kathryn A. , Hanley Patrick , Lovaglio Jamie , Saturday Greg , Edlefsen Paul T. , Khandhar Amit , Feldmann Heinz , Fuller Deborah Heydenburg , Erasmus Jesse H.
Published: August 2022

The global SARS-CoV-2 pandemic prompted rapid development of COVID-19 vaccines. Although several vaccines have received emergency approval through various public health agencies, the SARS-CoV-2 pandemic continues. Emergent variants of concern, waning immunity in the vaccinated, evidence that vaccines may not prevent transmission and inequity in vaccine distribution have driven continued development of vaccines against SARS-CoV-2 to address these public health needs. In this report, we evaluated a novel self-amplifying replicon RNA vaccine against SARS-CoV-2 in a pigtail macaque model of COVID-19 disease. We found that this vaccine elicited strong binding and neutralizing antibody responses. While binding antibody responses were sustained, neutralizing antibody waned to undetectable levels after six months but were rapidly recalled and conferred protection from disease when the animals were challenged 7 months after vaccination as evident by reduced viral replication and pathology in the lower respiratory tract, reduced viral shedding in the nasal cavity and lower concentrations of pro-inflammatory cytokines in the lung. Cumulatively, our data demonstrate in pigtail macaques that a self-amplifying replicon RNA vaccine can elicit durable and protective immunity to SARS-CoV-2 infection. Furthermore, these data provide evidence that this vaccine can provide durable protective efficacy and reduce viral shedding even after neutralizing antibody responses have waned to undetectable levels.
UNIQmin, an alignment-free tool to study viral sequence diversity across taxonomic lineages: a case study of monkeypox virus
Authors: Chong Li Chuin , Khan Asif M.
Published: August 2022

Sequence changes in viral genomes generate protein sequence diversity that enable viruses to evade the host immune system, hindering the development of effective preventive and therapeutic interventions. Massive proliferation of sequence data provides unprecedented opportunities to study viral adaptation and evolution. Alignment-free approach removes various restrictions, otherwise posed by an alignment-dependent approach for the study of sequence diversity. The publicly available tool, UNIQmin offers an alignment-free approach for the study of viral sequence diversity at any given rank of taxonomy lineage and is big data ready. The tool performs an exhaustive search to determine the minimal set of sequences required to capture the peptidome diversity within a given dataset. This compression is possible through the removal of identical sequences and unique sequences that do not contribute effectively to the peptidome diversity pool. Herein, we describe a detailed three-part protocol utilizing UNIQmin to generate the minimal set for the purpose of viral diversity analyses, alignment-free at any rank of the taxonomy lineage, using the latest global public health threat monkeypox virus (MPX) as a case study. This protocol enables systematic diversity study across the taxonomic lineage, which are much needed for our future preparedness of a viral epidemic, in particular when data is in abundance, freely available, and alignment is not an option.
IL-22/IL-22RA1 promotes human Tenon’s capsule fibroblasts proliferation and regulates fibrosis through STAT3 signaling pathway
Authors: Zhao Yang , Zhou Xiaoyu , Zhang Xinyue , Zhou Dengming , Chen Baihua , Duan Xuanchu
Published: August 2022

The study is aimed to investigate that the IL-22/IL-22RA1 signaling pathway regulates scar formation. A total of 31 glaucoma patients who had been previously treated with trabeculectomy surgery and the intraocular pressure was uncontrollable because of scarring and 19 strabismus patients as control patient group. ELISA showed that the IL-22 content of serum from glaucoma patients was 29.80±5.1 ng/μl which is higher than that 5.21±0.9 ng/μl from healthy group significantly. Serum from patients was used to incubate human Tenon’s capsule fibroblasts (HTFs) cells and IL-22 antibody rescued the effect of IL-22 on the biological functions. qPCR and western blot result showed that IL-22 mediates the biological function of HTFs cells via binding IL-22RA1 directly. When transfection of siR-IL-22RA1 or IL-22RA1 gene, the HTFs cells shown significantly anti-fibrosis or pro-fibrosis separately. By using STAT3 inhibitor BAY in IL-22RA1 overexpression group, IL-22-induced proliferation were reduced in HTFS cells. IL-22 promoted fibroblasts cell proliferation and α-SMA via IL-22/IL-22RA1/STAT3 signaling pathway, thereby potentially regulating glaucoma filtration trace fibrosis. This results also show the novel factor in process of postoperative scarring.

Summary Statement

The present study suggested that IL-22 expression in glaucoma patient after surgery. IL-22/IL-22RA1 signaling pathway promoted fibroblasts cell proliferation and α-SMA by activating the STAT3 signaling pathway, thereby potentially regulating glaucoma filtration trace fibrosis.
Crystallization and preliminary X-ray analysis of the C-type lectin domain of the spicule matrix protein SM50 from Strongylocentrotus purpuratus. Corrigendum
Authors: Ebenhoch Rebecca , Juneja Puneet , Rao Ashit , Cölfen Helmut , Diederichs Kay , Welte Wolfram
Published: August 2022

The identity of the crystallized protein in the article by Juneja et al. [(2014), Acta Cryst. F70, 260–262] is corrected.
Understanding relationship between topic selection and academic performance of scientific teams based on entity popularity trend
Authors: Zhang Tongyang , Tan Fang , Yu Chao , Wu Jiexun , Xu Jian
Published: August 2022

Purpose

Proper topic selection is an essential prerequisite for the success of research. To study this, this article proposes an important concerned factor of topic selection-topic popularity, to examine the relationship between topic selection and team performance.

Design/methodology/approach

The authors adopt extracted entities on the type of gene/protein, which are used as proxies as topics, to keep track of the development of topic popularity. The decision tree model is used to classify the ascending phase and descending phase of entity popularity based on the temporal trend of entity occurrence frequency. Through comparing various dimensions of team performance – academic performance, research funding, relationship between performance and funding and corresponding author's influence at different phases of topic popularity – the relationship between the selected phase of topic popularity and academic performance of research teams can be explored.

Findings

First, topic popularity can impact team performance in the academic productivity and their research work's academic influence. Second, topic popularity can affect the quantity and amount of research funding received by teams. Third, topic popularity can impact the promotion effect of funding on team performance. Fourth, topic popularity can impact the influence of the corresponding author on team performance.

Originality/value

This is a new attempt to conduct team-oriented analysis on the relationship between topic selection and academic performance. Through understanding relationships amongst topic popularity, team performance and research funding, the study would be valuable for researchers and policy makers to conduct reasonable decision making on topic selection.
Reasons for resistance to e-waste recycling: evidence from an emerging economy
Authors: Sajid Muhammed , Zakkariya K.A.
Published: August 2022

Purpose

The purpose of this paper, an empirical research, is to identify the psychological and functional barriers that result in e-waste recycling resistance.

Design/methodology/approach

The study is equipped with the theoretical lens of the innovation resistance theory. Households living in an Indian city were surveyed using a pre-validated questionnaire. Statistical analysis for the study was done with partial least squares – structural equation modeling.

Findings

The outcome of the survey exhibited that the significant factors contributing to e-waste recycling resistance are usage barrier, value barrier, risk barrier and tradition barrier.

Practical implications

The study offers implications for multiple stakeholders, which aid them in formulating strategies to overcome e-waste recycling resistance.

Originality/value

This research has remarkable importance as it is the pioneering study that extensively investigates the reasons for e-waste recycling resistance in an emerging economy. The study also empirically validates the moderating role of environmental awareness, age, gender and income in the relationship between barriers and resistance to e-waste recycling.
Joint board management meetings and earnings management
Authors: Agustia Dian , Harymawan Iman , Nasih Mohammad , Nowland John
Published: August 2022

Purpose

Joint board management meetings bring boards of directors and top management teams together to share information and discuss company matters. The authors investigate whether these joint meetings are associated with higher agency costs or information sharing benefits in the context of firm earnings management.

Design/methodology/approach

Using publicly disclosed data on the frequency of joint board management meetings in Indonesian firms, the authors examine the relationship between joint board management meetings and earnings management during 2010–2017.

Findings

The authors find that more joint board management meetings are associated with lower earnings management. This is consistent with joint board management meetings providing net information sharing benefits. Additional testing indicates that the results are the strongest when firms hold more joint board management meetings than regular board meetings.

Originality/value

The findings suggest that in addition to holding regular board and audit committee meetings, formal meetings between boards of directors and top management teams are beneficial to shareholders by restricting opportunistic accounting choices by firm management.
Does green intellectual capital affect green innovation performance? Evidence from the Spanish wine industry
Authors: Marco-Lajara Bartolomé , Zaragoza-Sáez Patrocinio Carmen , Martínez-Falcó Javier , Sánchez-García Eduardo
Published: August 2022

Purpose

The purpose of this study is to focus on analyzing how the set of green intangibles held by wineries and their members, i.e. green intellectual capital (GIC), affects green innovation performance (GIP). Specifically, the study aims to investigate how GIP is influenced by GIC through the mediating role of the variable knowledge management (KM) and corporate social responsibility (CSR).

Design/methodology/approach

The study proposes a conceptual model, based on previous studies, which is tested through structural equations (PLS-SEM) with data collected from 202 Spanish wineries.

Findings

The results of the research indicate that there is a positive and significant relationship between GIC and GIP. Furthermore, CSR and KM partially mediate the relationship between these two variables, playing a key role in the environmental management of wineries.

Originality/value

The present research, therefore, contributes to the literature in several ways. First, the study advances the understanding of GIC as well as its link with GIP. Second, the research aims to fill the gap in the literature through the study of CSR and KM as mediating variables in such a link. Third, to the best of the authors’ knowledge, the model proposed has not been previously addressed in the academic literature, thus representing an advance in scientific knowledge. Fourthly, no research has addressed the study of environmental intangibles in the wine industry, with this research, therefore, being a pioneer in contextualizing the study of GIC in this increasingly knowledge-intensive industry.
Integrating knowledge management and BIM for safety risk identification of deep foundation pit construction
Authors: Chen Dawei , Zhou Jianliang , Duan Pinsheng , Zhang Jiaqi
Published: August 2022

Purpose

The outbreak of COVID-19 pandemic has posed severe challenges to infrastructure construction in China. Particularly, the complex technology and high process uncertainty of deep foundation pit construction make its safety risk identification a challenging issue of general concern. To address these challenges, Building Information Modeling (BIM) can be used as an important tool to enhance communication and decision-making among stakeholders during the pandemic. The purpose of this study is to propose a knowledge management and BIM-integrated safety risk identification method for deep foundation pit construction to improve the management efficiency of project participants.

Design/methodology/approach

This paper proposes a risk identification method that integrates BIM and knowledge management for deep foundation pit construction. In the framework of knowledge management, the topological relationships between objects in BIM are extracted and visualized in the form of knowledge mapping. After that, formal expressions of codes are established to realize the structured processing of specification provisions and special construction requirements. A comprehensive plug-in for deep foundation pit construction is designed based on the BIM software.

Findings

The proposed method was verified by taking a sub-project in deep foundation pit project construction as an example. The result showed the new method can make full use of the existing specification and special engineering requirements knowledge. In addition, the developed visual BIM plug-in proves the feasibility and applicability of the proposed method, which can help to increase the risk identification efficiency and refinement.

Originality/value

The deep foundation pit safety risk identification is challenged by the confusion of deep foundation pit construction safety knowledge and the complexity of the BIM model. By establishing the standardized expression of normative knowledge and special construction requirements, the efficiency and refinement of risk identification are improved while ensuring the comprehensiveness of results. Moreover, the topology-based risk identification method focuses on the project objects and their relations in the way of network, eliminating the problem of low efficiency from the direct BIM-based risk identification method due to massive data.