bluuebunny/crossref_metadata_2025 huggingface dataset:
Alendronate Conjugate for Targeted Delivery to Bone-Forming Prostate Cancer
Authors: Damasco Jossana A. , Yu Guoyu , Kumar Ajay , Perez Joy , Lirag Rio Carlo M. , Whitley Elizabeth M. , Lin Sue-Hwa , Melancon Marites P.
Published: September 2022

Bone is the primary metastasis site for lethal prostate cancer, often resulting in poor prognosis, crippling pain, and diminished functioning that drastically reduce both quality of life and survivability. Uniquely, prostate cancer bone metastasis induces aberrant bone overgrowth, due to an increase of osteoblasts induced by tumor-secreted bone morphogenetic protein 4 (BMP4). Conjugating drugs to substances that target the tumor-induced bone area within the metastatic tumor foci would be a promising strategy for drug delivery. To develop such a strategy, we conjugated a near infrared (NIR) fluorescent probe, the dye Cy5.5, to serve as a surrogate for drugs, with alendronate, which targets bone. Characterization, such as infrared spectroscopy, confirmed the synthesis of the Cy5.5-ALN conjugate. The maximum absorbance of free Cy5.5, which was at 675 nm, did not change upon conjugation. Alendronate targeted the bone component hydroxyapatite in a dose-dependent manner up to 2.5 μM, with a maximum of 85% of Cy5.5-ALN bound to hydroxyapatite, while free Cy5.5 alone had 6% binding. In in vitro cell binding studies, Cy5.5-ALN bound specifically with mineralized bone matrix of differentiated MC3T3-E1 cells or 2H11 endothelial cells that were induced to become osteoblasts through endothelial-to-osteoblast transition, the underlying mechanism of prostate-cancer-induced bone formation. Neither Cy5.5-ALN nor free Cy5.5 bound to undifferentiated MC3T3-E1 or 2H11 cells. Bone-targeting efficiency studies in non-tumor-bearing mice revealed accumulation over time in the spine, jaw, knees, and paws injected with Cy5.5-ALN, and quantification showed higher accumulation in femurs than in muscle at up to 28 days, while the free Cy5.5 dye was observed circulating without preferential accumulation and decreased over time. There was a linear relationship with fluorescence when the injected concentration of Cy5.5-ALN was between 0.313 and 1.25 nmol/27 g of mouse, as quantified in mouse femurs both in vivo and ex vivo. Ex vivo evaluation of bone-targeting efficiency in nude mice was 3 times higher for bone-forming C4-2b-BMP4 tumors compared to non-bone-forming C4-2b tumors (p-value < 0.001). Fluorescence microscopy imaging of the tumors showed that Cy5.5-ALN co-localized with the bone matrix surrounding tumor-induced bone, but not with the viable tumor cells. Together, these results suggest that a drug-ALN conjugate is a promising approach for targeted delivery of drug to the tumor-induced bone area in the metastatic foci of prostate cancer.
PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application
Authors: Zhang Zhihao , Zhou Jinhu , Ni Peng , Hu Bing , Deng Shuang , Xiao Qian , He Qian , Li Gai , Xia Yan , Liu Mei , Wang Cong , Fang Zhizheng , Xia Nan , Zhang Zhe-Rui , Zhang Bo , Cai Kun , Jolicoeur Normand , Xu Yan , Liu Binlei
Published: September 2022

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and still has a considerable impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, the primary responsible for the host immune response upon infection. Here we show the preclinical studies of a broad protective SARS-CoV-2 subunit vaccine developed from our Trimer Domain platform using the Delta spike protein, from antigen design to purification, vaccine evaluation and manufacturability. The prefusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. The immunogenicity studies demonstrated that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous virus challenge. The neutralizing antibodies induced by this vaccine display a cross-reactive capacity against the ancestral WA1 and Delta variants as well as different Omicron, including BA.5.2. The Trimer Domain platform was proven to be a key technology in the rapid production of the PF-D-Trimer vaccine and may be crucial to accelerate the development of updated versions of SARS-CoV-2 vaccines.
Inference of differential gene regulatory networks from gene expression data using boosted differential trees
Authors: Galindez Gihanna , List Markus , Baumbach Jan , Blumenthal David B. , Kacprowski Tim
Published: September 2022

Diseases can be caused by molecular perturbations that induce specific changes in regulatory interactions and their coordinated expression, also referred to as network rewiring. However, the detection of complex changes in regulatory connections remains a challenging task and would benefit from the development of novel non-parametric approaches. We developed a new ensemble method called BoostDiff (boosted differential regression trees) to infer a differential network discriminating between two conditions. BoostDiff builds an adaptively boosted (AdaBoost) ensemble of differential trees with respect to a target condition. To build the differential trees, we propose differential variance improvement as a novel splitting criterion. Variable importance measures derived from the resulting models are used to reflect changes in gene expression predictability and to build the output differential networks. BoostDiff outperforms existing differential network methods on simulated data evaluated in two different complexity settings. We then demonstrate the power of our approach when applied to real transcriptomics data in COVID-19 and Crohn’s disease. BoostDiff identifies context-specific networks that are enriched with genes of known disease-relevant pathways and complements standard differential expression analyses. BoostDiff is available athttps://github.com/gihannagalindez/boostdiff_inference.

Author Summary

Gene regulatory networks, which comprise the collection of regulatory relationships between transcription factors and their target genes, are important for controlling various molecular processes. Diseases can induce perturbations in normal gene co-expression patterns in these networks. Detecting differentially co-expressed or rewired edges between disease and healthy biological states can be thus useful for investigating the link between specific disease-associated molecular alterations and phenotype. We developed BoostDiff (boosted differential trees), an ensemble method to derive differential networks between two biological contexts. Our approach applies a boosting scheme using differential trees as base learner. A differential tree is a new tree structure that is built from two expression datasets using a splitting criterion called the differential variance improvement. The resulting BoostDiff model learns the most differentially predictive features which are then used to build the directed differential networks. BoostDiff outperforms other differential network methods on simulated data and outputs more biologically meaningful results when evaluated on real transcriptomics datasets. BoostDiff can be applied to gene expression data to reveal new disease mechanisms or identify potential therapeutic targets.
Nanobodies for the treatment of SARS-CoV-2 in animals: a meta-analysis
Authors: Jiao Jiao , Lin Shulan , Liang Zhenqi , Wu Peng
Published: September 2022

This meta-analysis aimed to find the effect of variable domain of heavy-chain antibodies (VHHs) for the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in animals. The databases of the PubMed, China National Knowledge Infrastructure (CNKI), Wan fang data, Cochrane Library, and Embase were searched for articles published before August 2022 on the protective effects of VHHs in animals. The articles retrieved were screened using inclusion and exclusion criteria. The data were analyzed using Review Manager 5.4. Six articles were selected from 667 articles based on the inclusion and exclusion criteria in VHHs. A forest plot showed that VHHs could offer protection against SARS-CoV-2 infection in animals [Mantel-Haenszel (MH) = 172.94, 95% confidence interval (CI) = (43.96, 678.42), P < 0.00001]. There was almost no heterogeneity in this study (I2 = 0). A funnel plot showed that the bias of the data analysis was small. This is a special meta-analysis proved that VHHs could treat and prevent SARS-CoV-2 in animals.
Rejuvenation strategies share gene expression programs of reduced inflammation and downstream restored fatty acid metabolism
Authors: Landsberger Tomer , Amit Ido , Alon Uri
Published: September 2022

Understanding the mechanism of rejuvenation is central to aging research. No study has compared the effects of the four major rejuvenation strategies: senolytics, caloric restriction,in vivopartial cellular reprogramming and young/old blood factor exchange, which operate via different modalities. We use mice transcriptional data to compare them to each other and to normal aging. We find a shared gene expression program common to all rejuvenation strategies, in which inflammation declines and metabolism, especially of fatty acids, increases. An inverse signature occurs in normal aging. To test whether inflammation is upstream of the metabolic signature, we studied chronic inflammation in three different organs in young mice. Chronic inflammation was associated with a similar decline in metabolism, suggesting that inflammation is upstream of the metabolic signature. We find that inflammation may also underlie human transcriptional age calculator. We conclude that a core mechanism of rejuvenation acts through reduction of inflammation with downstream effects that enhance metabolism, attenuating the most robust age-related changes. This supports a notion of directly targeting genes associated with these pathways to mitigate age-related deterioration.
Prorenin from renal tubules is a major driver of diabetic kidney disease
Authors: Federlein Anna , Lehrmann Claudia , Tauber Philipp , Todorov Vladimir , Schweda Frank
Published: September 2022

The renin-angiotensin-system (RAS) plays a critical role in diabetic nephropathy, and inhibitors of the RAS are central components in its therapy. Renin circulates in the blood in its active form but also in the form of its enzymatically inactive precursor prorenin. In humans, the plasma prorenin concentration exceeds that of active renin several times. While the plasma concentration of active renin is unchanged or even reduced in diabetic patients, the prorenin concentration increases significantly and it has been shown that high prorenin levels are associated with diabetic microvascular damage. Why prorenin increases in diabetes while active renin is reduced is unclear. Previous studies suggest that there may be formation of prorenin in the tubular system of diabetic kidneys. To investigate the functional consequences of possible tubular renin formation in diabetes, we generated mice with inducible tubule-specific deletion of the renin gene (tubule-renin KO).

Under control conditions, tubule-renin KO had no apparent phenotype and plasma and tissue levels of renin and prorenin were similar to those of mice with intact tubular renin (control mice). In control mice type-1 diabetes (streptozotocin, STZ) for 8 to 12 weeks stimulated tubular renin mRNA and protein expression, especially in distal nephron segments including collecting ducts. This increase in renin synthesis in renal tubules was markedly attenuated or even absent in tubule-renin KO mice. Similar to diabetic patients, plasma prorenin was markedly elevated in diabetic control mice. This stimulation of plasma prorenin was absent in mice with tubule-specific deletion of the renin gene. Moreover, the high prorenin levels in renal tissue, which were observed in diabetic control mice, were markedly reduced in tubule-renin KO. Noteworthy, plasma renin activity was not reduced in tubule-renin KO compared with controls, suggesting that renal tubules of diabetic mice mainly release prorenin. Kidneys of control mice with intact tubular renin showed classical signs of diabetic renal damage, such as albuminuria, mesangial expansion, fibrosis, inflammation and capillary rarefaction. All of these parameters were significantly ameliorated in tubule-renin KO, indicating that tubular renin, most likely in its prorenin form, significantly aggravates renal damage in diabetes.

These data provide clear evidence for the first time that the tubular renin system is an additional source for circulating prorenin in diabetes, hereby providing an explanation for the paradox regulation of active renin and prorenin in diabetes. Moreover, the data show that tubular renin markedly contributes to the progression of diabetic nephropathy.
IBRAP: Integrated Benchmarking Single-cell RNA-sequencing Analytical Pipeline
Authors: Knight Connor H. , Khan Faraz , Gill Upkar , Wang Jun
Published: September 2022

Single-cell RNA-sequencing (scRNA-seq) is a powerful tool to study cellular heterogeneity. The high dimensional data generated from this technology are complex and require specialised expertise for analysis and interpretation. The core of scRNA-seq data analysis contains several key analytical steps, which include pre-processing, QC, normalisation, dimensionality reduction, integration, and clustering. Each step often has many algorithms developed with varied underlying assumptions and implications. With such a diverse choice of tools available, benchmarking analyses have compared their performances and demonstrated that tools differentially operate according to the data types and complexity. Here, we present Integrated Benchmarking scRNA-seq Analytical Pipeline (IBRAP) – a tool, which contains a range of analytical components that can be interchanged throughout the pipeline alongside multiple benchmarking metrics that enables users to compare results and determine the optimal pipeline combinations for their data. We apply IBRAP to single and multi-sample integration analysis using pancreas, cell line and simulated data accompanied with ground truth cell labels, demonstrating the interchangeable and benchmarking functionality of IBRAP. Our results confirm that the optimal pipelines are dependant of individual samples and studies, further supporting the rationale and necessity of our tool. We then compare reference-based cell annotation with unsupervised analysis, both included in IBRAP, and demonstrate the superiority of the reference-based method in identifying robust major and minor cell types. Thus, IBRAP presents a valuable tool to integrate multiple samples and studies to create reference maps of normal and diseased tissues, facilitating novel biological discovery using the vast volume of scRNA-seq data available.
Placental treatment with insulin-like growth factor 1 via nanoparticle differentially impacts vascular remodeling factors in guinea pig sub-placenta/decidua
Authors: Davenport Baylea , Jones Helen N. , Wilson Rebecca L.
Published: September 2022

Clinically, fetal growth restriction (FGR) is only detectable in later gestation, despite pathophysiological establishment likely earlier in pregnancy. Additionally, there are no effective in utero treatment options for FGR. We have developed a nanoparticle to deliver human insulin-like 1 growth factor (hIGF-1) in a trophoblast-specific manner which results in increased expression of hIGF-1. IGF-1 signaling in the placenta regulates multiple developmental processes including trophoblast invasion and maternal vascular remodeling, both of which can be diminished in the FGR placenta. We aimed to determine the effects of short-term hIGF-1 nanoparticle treatment on sub-placenta/decidua trophoblast signaling mechanisms in FGR and under normal growth conditions. Using the guinea pig maternal nutrient restriction (MNR) model of FGR, ultrasound-guided, intra-placenta injections of hIGF-1 nanoparticle were performed at gestational day 30-33, and dams sacrificed five days later. Sub-placenta/decidua tissue was separated from placenta for further analyses. Western blot was used to analyze protein expression of ERK/AKT/mTOR signaling proteins (phospho-Erk (pErk), phospho-Akt (pAkt), raptor, rictor and deptor). qPCR was used to analyze gene expression of vascular/remodeling factors (vascular endothelial growth factor (Vegf), placenta growth factor (Pgf), platelet-derived growth factor (Pdgf)) and tight junction/adhesion proteins (claudin 5 (Cldn5), p-glycoprotein (Abcb1), occludin (Ocln) and tight junction protein 1 (Zo1)). MNR reduced expression of pErk, PdgfB and Cldn5, and increased expression of Ocln and Zo1 in the sub-placenta/decidua. In MNR + hIGF1 nanoparticle sub-placenta/decidua, expression of PdgfB, Ocln and Zo1 was normalized, whilst pAkt, VegfB, Vegf receptor 1 and PdgfB receptor were increased compared to MNR. In contrast, hIGF-1 nanoparticle treatment of normal placentas reduced expression of pErk, raptor and increased expression of the mTOR inhibitor deptor. This was associated with reduced expression of VegfA, Plgf, and PdgfB. Here we have shown that the impact of hIGF-1 nanoparticle treatment is dependent on pregnancy environment. Under MNR/FGR, hIGF-1 nanoparticle treatment triggers increased expression of growth factors and normalization of EMT factors. However, under normal conditions, the response of the placenta is to decrease AKT/mTOR signaling and growth factor expression to achieve homeostasis.
Sequencing of Monkeypox virus from infected patients reveals viral genomes with APOBEC3-like editing, gene inactivation, and bacterial agents of skin superinfection
Authors: Colson Philippe , Penant Gwilherm , Delerce Jeremy , Boschi Céline , Wurtz Nathalie , Branger Stéphanie , Lagier Jean-Christophe , Cassir Nadim , Tissot-Dupont Hervé , Million Matthieu , Aherfi Sarah , Scola Bernard LA
Published: September 2022

An epidemic of Monkeypox virus (MPX virus) infections has arisen in May 2022 in non-endemic countries particularly in Europe among men having sex with men, whose extent is unprecedented. Since May 2022 we implemented MPX virus diagnosis by real-time PCR at university hospitals of Marseille, southern France. Here, we performed DNA metagenomic analyses of clinical samples from MPX virus-infected patients between June and July 2022, using next-generation sequencing with Illumina or Nanopore technologies. Twenty-five samples from 25 patients were studied. This allowed obtaining a MPX virus genome for 18 patients, essentially from genital skin lesions and rectal swabbing. All 18 genomes were classified in the MPX virus B.1 lineage, and we delineated five sublineages (A-E). We detected a high number of mutations (66-73) scattered along the MPX virus genomes relatively to the genome obtained from a human in Nigeria in 2018. Some non-synonymous mutations occurred in genes encoding central proteins, among which transcription factors and core and envelope proteins. They included two mutations that truncate RNA polymerase subunit RPO132 and a phospholipase D-like protein, which suggests gene inactivation. In addition, we identified that a large majority of nucleotide substitutions (94%) in the 18 MPX virus genomes were G>A or C>T, suggesting the action of human APOBEC3 enzymes. Finally, while we did not detect reads matching with main bacterial agents of sexually transmitted infections, >1,000 reads identified Staphylococcus aureus and Streptococcus pyogenes for 7 and 17 samples, respectively. These findings warrant a close genomic monitoring of MPX virus to get a better picture of this virus’ genetic evolution and mutational patterns, and they point out the common presence in monkeypox lesions of bacterial agents of skin superinfection, which warrants a close clinical monitoring in monkeypox patients.
PBP1A directly interacts with the divisome complex to promote septal peptidoglycan synthesis in Acinetobacter baumannii
Authors: Kang Katie N. , Boll Joseph M.
Published: September 2022

The class A penicillin-binding proteins (aPBPs), PBP1A and PBP1B, are major peptidoglycan synthases that synthesize more than half of the peptidoglycan per generation in Escherichia coli. Whereas aPBPs have distinct roles in peptidoglycan biosynthesis during growth (i.e., elongation and division), they are semi-redundant; disruption of either is rescued by the other to maintain envelope homeostasis and promote proper growth. Acinetobacter baumannii is a nosocomial pathogen that demonstrated a high propensity to overcome antimicrobial treatment. A. baumannii encodes both PBP1A and PBP1B (encoded by mrcA and mrcB, respectively), but only mrcA deletion decreased fitness and contributed to colistin resistance through inactivation of lipooligosaccharide biosynthesis, indicating that PBP1B was not functionally redundant with PBP1A activity. While previous studies suggested a distinct role for PBP1A in division, it was unknown if its role in septal peptidoglycan biosynthesis was direct. Here, we show that A. baumannii PBP1A has a direct role in division through interactions with divisome components. PBP1A localizes to septal sites during growth, where it interacts with the transpeptidase, PBP3, an essential division component that regulates daughter cell formation. PBP3 overexpression was sufficient to rescue the division defect in ΔmrcA A. baumannii; however, PBP1A overexpression was not sufficient to rescue the septal defect when PBP3 was inhibited, suggesting their activity is not redundant. Overexpression of a major DD-carboxypeptidase, PBP5, also restored the canonical A. baumannii coccobacilli morphology in ΔmrcA cells. Together, these data support a direct role for PBP1A in A. baumannii division and highlights its role as a septal peptidoglycan synthase.

Importance

Peptidoglycan biosynthesis is a validated target of β-lactam antibiotics, and it is critical that we understand essential processes in multidrug resistant pathogens such as Acinetobacter baumannii. While model systems such as Escherichia coli have shown that PBP1A is associated with side wall peptidoglycan synthesis, we show herein that A. baumannii PBP1A directly interacts with the divisome component PBP3 to promote division, suggesting a unique role for the enzyme in the highly drug resistant nosocomial pathogen. A. baumannii demonstrated unanticipated resistance and tolerance to envelope-targeting antibiotics, which may be driven by rewired peptidoglycan machinery, and may underlie therapeutic failure during antibiotic treatment.
Are Maximum Yields sustainable? Effect of intra-annual time-scales on MSY, stability and resilience
Authors: Ricouard Antoine , Lehuta Sigrid , Mahévas Stéphanie
Published: September 2022

The concept of Maximum Sustainable Yield (MSY) have been lying at the core of the theory of sustainable harvesting a fishery for decades and have become a key reference point for many fishing administrations, including the European Union. However, the existence of a MSY relies on the stability of a population equilibrium. This hypothesis, though always true in the original Schaeffer model, is still challenging in more realistic and recent population models. However, recent advances shows that fish population can exhibit complex dynamics that are ill described by the classical theory. In particular, processes occurring at intra-annual time scales can affect the stability of a population equilibrium even in a strictly single species case. Associated to stability, the resilience of the equilibrium (defined as an inverse return-time following a perturbation) also matters in a management purpose. Here, we introduce an analytical single population model in discrete time with a monthly time-step allowing temporal distinction between maturation and recruitment with density-dependent mortality and fishing exploitation. We show that, thanks to an appropriate population structure, we can easily derive inter-annual population equilibrium, and study their resilience and stability properties. Then, we show that under classical hypothesis concerning density-dependence, equilibrium stability is not guaranteed and that MSY can, in theory, be associated to unstable or low resilient states. However such destabilisation seems unlikely with realistic sets of parameters. Finally, a numerical illustration for sole (Solea solea) of the Bay of Biscay suggests that the value of MSY was sensitive to maturation period whereas viability, stability and resilience was more sensitive to timing of recruitment. The value ofFMSYappeared robust to uncertainty concerning maturation and recruitment. We conclude by saying that even if the risk of destabilisation is low for real populations, the risk of decreased resilience near the border of extinction should be cared of.
Ten new high-quality genome assemblies for diverse bioenergy sorghum genotypes
Authors: Voelker William G. , Krishnan Krittika , Chougule Kapeel , Alexander Louie C. , Lu Zhenyuan , Olson Andrew , Ware Doreen , Songsomboon Kittikun , Ponce Cristian , Brenton Zachary W. , Boatwright J. Lucas , Cooper Elizabeth A.
Published: September 2022

Sorghum (Sorghum bicolor (L.) Moench) is an agriculturally and economically important staple crop that has immense potential as a bioenergy feedstock due to its relatively high productivity on marginal lands. To capitalize on and further improve sorghum as a potential source of sustainable biofuel, it is essential to understand the genomic mechanisms underlying complex traits related to yield, composition, and environmental adaptations. Expanding on a recently developed mapping population, we generated de novo genome assemblies for 10 parental genotypes from this population and identified a comprehensive set of over 24 thousand large structural variants (SVs) and over 10.5 million single nucleotide polymorphisms (SNPs).These resources can be integrated into both ongoing and future mapping and trait discovery for sorghum and its myriad uses including food, feed, bioenergy, and increasingly as a carbon dioxide removal mechanism. We show that SVs and nonsynonymous SNPs are enriched in different gene categories, emphasizing the need for long read sequencing in crop species to identify novel variation. Furthermore, we highlight SVs and SNPs occurring in genes and pathways with known associations to critical bioenergy-related phenotypes and characterize the landscape of genetic differences between sweet and cellulosic genotypes.
A national professional development program fills mentoring gaps for postdoctoral researchers
Authors: Sun Ting , Drane Denise , McGee Richard , Campa Henry , Goldberg Bennett B , Hokanson Sarah Chobot
Published: September 2022

The Postdoc Academy: Succeeding as a Postdocwas designed to build postdocs’ skills in career transition, career planning, collaborative research, resilience, and self-reflection. This study examined self-reported changes in five skills as learners progressed through the course. Data were collected from participants who responded to both pre- and post-surveys and engaged with the course learning activities. Results from repeated measures multivariate analysis of variance revealed that all of the self-reported perceptions of skills improved significantly upon completion of the course. Hierarchical regressions revealed that underrepresented minority learners had greater gains in their development of skills in career planning, resilience, and self-reflection. Qualitative analysis of learners’ responses to learning activities found that postdocs perceived networking and mentor support as contributing factors to their skill advancement while tensions among multiple obligations and concerns of uncertainties were significant challenges to applying those skills.
ATR protects centromere identity by promoting DAXX association with PML nuclear bodies
Authors: Trier Isabelle , Joo Yoon Ki , Black Elizabeth , Kabeche Lilian
Published: September 2022

Centromere protein A (CENP-A) defines centromere identity and nucleates kinetochore formation for mitotic chromosome segregation. Here, we show that Ataxia telangiectasia and Rad3-related (ATR) kinase, a master regulator of the DNA damage response, protects CENP-A occupancy at interphase centromeres in a DNA damage-independent manner. As ATR localizes to promyelocytic leukemia nuclear bodies (PML NBs) in unperturbed cells, we hypothesized that ATR protects CENP-A occupancy by regulating the localization of the histone H3.3 chaperone and PML NB component, DAXX. Indeed, we found that ATR inhibition reduces DAXX association with PML NBs, resulting in the DAXX-dependent loss of CENP-A from interphase centromeres. Lastly, we demonstrate that CENP-A occupancy is not restored until G1 of the following cell cycle, leading to increased mitotic chromosome segregation defects. These findings demonstrate a novel mechanism by which ATR protects centromere identity and genome stability.
Socioeconomics and biogeography jointly drive geographic biases in our knowledge of plant traits: a global assessment of the Raunkiærian shortfall in plants
Authors: Maitner Brian , Gallagher Rachael , Svenning Jens-Christian , Tietje Melanie , Wenk Elizabeth H. , Eiserhardt Wolf L.
Published: September 2022

The traits of plants determine how they interact with each other and their environment, constituting key knowledge for diverse fields. The lack of comprehensive knowledge of plant traits (the “Raunkiærian shortfall”) poses a major, cross-disciplinary, barrier to scientific advancement. Spatial biases in trait coverage may also lead to erroneous conclusions affecting ecosystem management and conservation planning. Thus, there is an urgent need to assess the spatial completeness of plant trait data, understand drivers of geographic biases, and to identify solutions for filling regional gaps. Here, we leverage a comprehensive set of regional species checklists for vascular plants and trait data for 2,027 traits and 128,929 plant species from the TRY database to assess trait data completeness across the globe. We show that trait data availability in TRY is associated with socioeconomic and biological factors influencing sampling likelihood: trait completeness was positively associated with mean species range size, research expenditure, and human population density and negatively associated with endemism and vascular plant species richness. Integration of a second, regional trait database (AusTraits) more than doubled trait completeness for the continent covered, indicating that the creation and integration of regional databases can rapidly expand trait completeness.

Plain Language Summary

The traits of plants determine how they interact with each other and their environment. Our knowledge of plant traits is incomplete, limiting scientific advancement as well as our ability to manage ecosystems and plan conservation actions. We show that there are large biases in trait data availability which are associated with both biological factors (range size, endemism, species richness) and socioeconomic factors (research expenditure, human population density). We also show how regionally-focused efforts can help rapidly expand trait data availability.
Multi-factorial examination of amplicon sequencing workflows from sample preparation to bioinformatic analysis
Authors: De Wolfe Travis J. , Wright Erik S.
Published: September 2022

The development of sequencing technologies to evaluate bacterial microbiota composition has allowed new insights into the importance of microbial ecology. However, the variety of methodologies used among amplicon sequencing workflows leads to uncertainty about best practices as well as reproducibility and replicability among microbiome studies. Using a bacterial mock community composed of 37 soil isolates, we performed a comprehensive methodological evaluation of 540 workflows, each with a different combination of methodological factors spanning sample preparation to bioinformatic analysis to define sources of artifacts that affect sensitivity, specificity, and biases in the resulting compositional profiles. Of the 540 workflows examined, those using the V4-V4 primer set enabled the highest level of concordance between the original mock community and resulting microbiome sequence composition. Use of a high-fidelity polymerase, or a lower-fidelity polymerase with increased PCR elongation time limited chimera formation. Bioinformatic pipelines presented a trade-off between the fraction of distinct community members identified (sensitivity) and fraction of correct sequences (specificity). DADA2 and QIIME2 assembled V4-V4 reads amplified by Taq polymerase resulted in the highest specificity (100%), but only identified 52% of mock community members. Using mothur to assemble and denoise V4-V4 reads resulted in detection of 75% of mock community members among the resulting sequences, albeit with marginally lower specificity (99.5%). Optimization of microbiome workflows is critical for accuracy and to support reproducibility and replicability among microbiome studies. These aspects will help reveal the guiding principles of microbial ecology and impact the translation of microbiome research to human and environmental health.
A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice
Authors: Hackstein Carl-Philipp , Costigan Dana , Drexhage Linnea , Pearson Claire , Bullers Samuel , Ilott Nicholas , Akther Hossain Delowar , Gu Yisu , FitzPatrick Michael E.B. , Harrison Oliver J. , Garner Lucy C. , Mann Elizabeth H. , Pandey Sumeet , Friedrich Matthias , Provine Nicholas M. , Uhlig Holm , Marchi Emanuele , Powrie Fiona , Klenerman Paul , Thornton Emily E.
Published: September 2022

Interactions with commensal microbes shape host immunity on multiple levels and are recognized to play a pivotal role in human health and disease. In this study, we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics typically associated with innate-like T cells, including the expression of the key transcription factor PLZF and the ability to respond to cytokines including IL-12, IL-18 and IL-23 in a TCR-independent manner. TheseMHC-II restricted,innate-like,commensal-reactive T cells (TMIC) are endowed with a polyfunctional effector potential spanning classic Th1- and Th17-cytokines, cytotoxic molecules as well as regulators of epithelial homeostasis and represent an abundant and conserved cell population in the human and murine colon. T cells with the TMICphenotype were increased in ulcerative colitis patients and their presence aggravated pathology in DSS-treated mice, pointing towards a pathogenic role in colitis. Our findings add TMICcells to the expanding spectrum of innate-like immune cells positioned at the frontline of intestinal immune surveillance, capable of acting as sentinels of microbes and the local cytokine milieu.
Vaccine effectiveness for preventing COVID-19 hospital admission during pregnancy: a population-based cohort study in England during the Alpha and Delta waves of the SARS-CoV-2 pandemic
Authors: Bosworth Matthew L. , Schofield Ryan , Ayoubkhani Daniel , Charlton Loes , Nafilyan Vahé , Khunti Kamlesh , Zaccardi Francesco , Gillies Clare , Akbari Ashley , Knight Marian , Wood Rachael , Hardelid Pia , Zuccolo Luisa , Harrison Camille
Published: September 2022

Objective

To estimate vaccine effectiveness (VE) for preventing COVID-19 hospital admission in women first infected with SARS-CoV-2 during pregnancy, and assess how this compares to VE among women of reproductive age who were not pregnant when first infected.

Design

Population-based cohort study using national, linked Census and administrative data.

Setting

England, United Kingdom, from 8th December 2020 to 31st August 2021.

Participants

815,4777 women aged 18 to 45 years (mean age, 30.4 years) who had documented evidence of a first SARS-CoV-2 infection in NHS Test and Trace data or Hospital Episode Statistics.

Main outcome measures

A hospital inpatient episode where COVID-19 was recorded as the primary diagnosis. Cox proportional hazards models, adjusted for calendar time of infection and sociodemographic factors related to vaccine uptake and risk of severe COVID-19, were used to estimate VE as the complement of the hazard ratio for COVID-19 hospital admission.

Results

Compared with unvaccinated pregnant women, the adjusted rate of COVID-19 hospital admission was 76% (95% confidence interval 69% to 82%) lower for single-vaccinated pregnant women and 83% (75% to 88%) lower for double-vaccinated pregnant women. These estimates were similar to those found for non-pregnant women: 79% (76% to 81%) for single-vaccinated and 82% (80% to 83%) for double-vaccinated. Among those vaccinated more than 90 days before infection, being double-vaccinated was associated with a greater reduction in risk than being single-vaccinated.

Conclusions

COVID-19 vaccination is associated with reduced rates of severe illness in pregnant women infected with SARS-CoV-2, and the reduction in risk is similar to that for non-pregnant women. Waning of vaccine effectiveness occurs more quickly after one dose of a vaccine than two doses.

What is already known on this topic

Being pregnant is a risk factor for severe illness and mortality following infection with SARS-CoV-2.

Existing evidence suggests that COVID-19 vaccines are effective for preventing severe outcomes in pregnant women.

However, research directly comparing vaccine effectiveness between pregnant and non-pregnant women of reproductive age at the population level are lacking.

What this study adds

Our study provides real-world evidence that COVID-19 vaccination reduces the risk of hospital admission by a similar amount for both women infected with SARS-CoV-2 during pregnancy and women who were not pregnant when infected, during the Alpha and Delta dominant periods in England.
Direct modelling from GPS data reveals daily-activity-dependency of effective reproduction number in COVID-19 pandemic
Authors: Ozaki Jun’ichi , Shida Yohei , Takayasu Hideki , Takayasu Misako
Published: September 2022

During the COVID-19 pandemic, governments faced difficulties in implementing mobility restriction measures, as no clear quantitative relationship between human mobility and infection spread in large cities is known. We developed a model that enables quantitative estimations of the infection risk for individual places and activities by using smartphone GPS data for the Tokyo metropolitan area. The effective reproduction number is directly calculated from the number of infectious social contacts defined by the square of the population density at each location. The difference in the infection rate of daily activities is considered, where the ‘stay-out’ activity, staying at someplace neither home nor workplace, is more than 28 times larger than other activities. Also, the contribution to the infection strongly depends on location. We imply that the effective reproduction number is sufficiently suppressed if the highest-risk locations or activities are restricted. We also discuss the effects of the Delta variant and vaccination.
Green governmentality and climate change risk management: the case of a regulatory reform in Bangladesh
Authors: Rana Tarek , Lowe Alan , Azam Md Saiful
Published: September 2022

Purpose

This study examines green investment reforms carried out in Bangladesh. The reform process curated significant changes by promoting green investment and fostering the adoption of risk management (RM) rationalities. This study’s focus is on revealing changes in behaviour and explaining how RM can act as an effective generator of climate change mitigation practices.

Design/methodology/approach

Building on Foucault's concept of governmentality, the authors apply a “green governmentality” interpretive lens to analyse interviews and documentary evidence, adopting a qualitative case study approach. The authors explore how green governmentality generates RM rationalities and techniques to induce policies and practices within banks and financial institutions (FIs) for climate change mitigation purposes.

Findings

The findings provide valuable insights into the reform process and influence of RM rationalities in the context of environmental concerns. The authors find that the reforms and creation of RM rationalities affect the management of climate mitigation practices within banks and FIs and identify the processes through which the RM techniques are transformed as climate concerns are emphasised. The authors illustrate green governmentality as persuasive strategies, which have generated specific ways of seeing climate change reality and new ways of inserting RM into organisational activities, through the green governmentality effects they created. These reforms made climate change actionable and governable through the production of RM rationalities, supported by accounting conceptualisations and processes.

Research limitations/implications

The insights from this study can assist with how we act upon questions of climate change from an RM perspective. Governments, policymakers and regulators who develop climate change-related laws, regulations and policies can draw on these insights to help foster green governmentality for climate change mitigation actions informed by RM practices.

Originality/value

This study offers insights into how climate change is not simply a biophysical reality but a site of power-knowledge dynamics where RM rationalities are constructed, and accounting processes are transformed. The authors show the application of RM and accounting efforts to change investment practices and how changes were encouraged and promoted by using regulation as a persuasive force on knowledgeable subjects rather than a repressive or oppressive power. The analytic power of green governmentality can be applied to increase understanding of how RM rationality contribute to the creation of useful conceptualisations of climate change and provide insights into how organisations respond to green governmentality.
Analysis of the influence of day and night temperature difference on oxygen concentration in ullage space of fuel tank
Authors: Zhang Ruihua , Liu Weihua
Published: September 2022

Purpose

Determining the variation law of the oxygen concentration in the ullage space of the fuel tank is the key to the design of the inert system. Among various factors affecting the oxygen concentration in the ullage space of the fuel tank, the temperature difference between day and night shows particular importance while relevant analysis and calculation are scarce.

Design/methodology/approach

This study establishes a theoretical simulation model of the central wing fuel tank of an aircraft according to the relevant provisions of day-night temperature variation in FAR25 airworthiness regulations, verifies the model with the existing experimental data and discusses the corresponding relationship between the oxygen concentration in the ullage space of the fuel tank and the day-night temperature difference. The influence of day and night temperature difference, fuel type, fuel load rate, initial oxygen concentration, dissolved oxygen evolution and other factors on the oxygen concentration in the ullage space of the fuel tank were analyzed, and the limit of initial oxygen concentration of the fuel tank before the shutdown at night meeting the requirements of the airworthiness provisions was proposed.

Findings

The results show that the temperature difference between day and night, fuel load rate, initial oxygen concentration and other factors have different effects on the oxygen concentration in the ullage space of fuel tank. The initial oxygen concentration limit before shutdown shall be 2% below the 12% oxygen concentration stipulated by FAA.

Research limitations/implications

The research results in this paper will be of good reference value to the design of the inert system and the calculation of the flammability exposure evaluation time. This paper aims to be good reference of the design of the inert system and the calculation of the flammability exposure evaluation time.

Originality/value

The research results of this paper can provide practical guidance for the current civil airworthiness certification work.
Automatic management of electrical loads in more electric aircraft
Authors: Fan Zhiyong , Zhao Zhen , Liu Zhexu
Published: September 2022

Purpose

This paper aims to automatically generate load shedding sequences due to insufficient power supply, to ensure flight safety and complete flight task.

Design/methodology/approach

In this paper, a power allocation and load management model, including logical and physical submodels of the distribution system, is first established according to different requirements of the loads in different flight phase and the current total power supply. Then, an optimal load management scheme based on an improved ant colony algorithm is proposed to automatically generate load shedding sequences for both safety-critical and nonsafety critical loads, to achieve a reliable and safe power supply.

Findings

To verify the efficiency and feasibility of the algorithm, the proposed method is verified in a virtual simulation platform. Simulation result illustrates that the proposed algorithm is efficient and feasible.

Practical implications

The proposed method can provide guidance on load power supply when the civil aircraft is under abnormal power supply situation.

Originality/value

An optimal load management scheme is proposed by considering different requirements of the loads in different flight phase and the current total power supply.
Conceptualising the panic buying phenomenon during COVID-19 as an affective assemblage
Authors: Zaky Ahmed , Mohamed Hassan , Saxena Gunjan
Published: September 2022

Purpose

This study aims to conceptualise the panic buying behaviour of consumers in the UK during the novel COVID-19 crisis, using the assemblage approach as it is non-deterministic and relational and affords new ways of understanding the phenomenon.

Design/methodology/approach

The study undertakes a digital ethnography approach and content analysis of Twitter data. A total of 6,803 valid tweets were collected over the period when panic buying was at its peak at the beginning of the first lockdown in March 2020.

Findings

The panic buying phase was a radical departure from the existing linguistic, discursive, symbolic and semiotic structures that define routine consumer behaviour. The authors suggest that the panic buying behaviour is best understood as a constant state of becoming, whereby stockpiling, food waste and a surge in cooking at home emerged as significant contributors to positive consumer sentiments.

Research limitations/implications

The authors offer unique insights into the phenomenon of panic buying by considering DeLanda’s assemblage theory. This work will inform future research associated with new social meanings of products, particularly those that may have been (re)shaped during the COVID-19 crisis.

Practical implications

The study offers insights for practitioners and retailers to lessen the intensity of consumers’ panic buying behaviour in anticipation of a crisis and for successful crisis management.

Originality/value

Panic buying took on a somewhat carnivalesque hue as consumers transitioned to what we consider to be atypical modes of purchasing that remain under-theorised in marketing. Using the conceptual lenses of assemblage, the authors map bifurcations that the panic buyers’ assemblages articulated via material and immaterial bodies.