bluuebunny/crossref_metadata_2025 huggingface dataset:
Pericardial & Mediastinal Fat-Associated Lymphoid Clusters are rapidly activated in an alkane induced model of Systemic Lupus Erythematosus
Authors: Bentkowska Karolina , Hardgrave Alex , Iqbal Nadia , Gresty Laura , Marsden Bethany , Macharia Sheila , Jackson-Jones Lucy
Published: July 2023

Systemic Lupus Erythematosus (SLE) is an autoimmune disease predominated by auto-antibodies that recognise cellular components. Pleural involvement is the most common SLE-related lung disease. Natural antibodies are rapidly secreted by innate-like B cells following perturbation of homeostasis and are important in the early stages of immune activation. The serous cavities are home to large numbers of innate-like B cells present both within serous fluid and resident within fat-associated lymphoid clusters (FALCs). FALCs are important hubs for B-cell activation and local antibody secretion within the body cavities. Patients with SLE can develop anti-phospholipid antibodies and in rare situations develop alveolar haemorrhage. Utilising delivery of the hydrocarbon oil pristane in C57BL/6 mice as a model of SLE we identify a rapid expansion of pleural cavity B cells as early as day 3 after intra-peritoneal pristane delivery. Following pristane delivery, pericardial B1 B cells are proliferative, express the plasma-cell surface marker CD138 and secrete both innate and class switched antibodies highlighting that this cavity niche may play an unrecognised role in the initiation of lupus pleuritis.

Graphical abstract
Coordination of gaze and action during high-speed steering and obstacle avoidance
Authors: Powell Nathaniel , Marshall Xavier , Diaz Gabriel J. , Fajen Brett R
Published: July 2023

When humans navigate through complex environments, they coordinate gaze and steering to efficiently sample the visual information needed to guide movement. Gaze and steering behavior during high-speed self-motion has been extensively studied in the context of automobile driving along a winding road. Theoretical accounts that have emerged from this work capture behavior during movement along explicit, well-defined paths over flat, obstacle-free ground surfaces. However, humans are also capable of visually guiding self-motion over uneven terrain that is cluttered with obstacles and may lack an explicit path. An extreme example of such behavior occurs during first-person view drone racing, in which pilots maneuver at high speeds through a dense forest. In this study, we explored the gaze and steering behavior of skilled drone pilots. Subjects guided a simulated quadcopter along a racecourse embedded within a forest-like virtual environment built in Unity. The environment was viewed through a head-mounted display while gaze behavior was recorded using an eye tracker. In two experiments, subjects performed the task in multiple conditions that varied in terms of the presence of obstacles (trees), waypoints (hoops to fly through), and a path to follow. We found that subjects often looked in the general direction of things that they wanted to steer toward, but gaze fell on nearby objects and surfaces more often than on the actual path or hoops. Nevertheless, subjects were able to perform the task successfully, steering at high speeds while remaining on the path, passing through hoops, and avoiding collisions. Furthermore, in conditions that contained hoops, subjects adapted how they approached the most immediate hoop in anticipation of the position (but not the orientation) of the subsequent hoop. Taken together, these findings challenge existing models of steering that assume that steering is tightly coupled to where actors look.
Biosynthesis of novel desferrioxamine derivatives requires unprecedented crosstalk between separate NRPS-independent siderophore pathways
Authors: Su Li , Souaibou Yaouba , Hôtel Laurence , Paris Cédric , Weissman Kira J. , Aigle Bertrand
Published: July 2023

Iron is essential to many biological processes, but its poor solubility in aerobic environments restricts its bioavailability. To overcome this limitation, bacteria have evolved a variety of strategies, including the production and secretion of iron-chelating siderophores. Here, we describe the discovery of four series of siderophores fromStreptomyces ambofaciensATCC23877, three of which are unprecedented. MS/MS-based molecular networking revealed that one of these series corresponds to acylated desferrioxamines (acyl-DFOs) recently identified fromS. coelicolor. The remaining sets include unprecedented tetra- and penta-hydroxamate acyl-DFO derivatives, all of which incorporate a previously undescribed building block. Stable isotope labeling and gene deletion experiments provide evidence that biosynthesis of the acyl-DFO congeners requires unprecedented crosstalk between two separate NRPS-independent siderophore (NIS) pathways in the producing organism. The new derivatives, whose biological role(s) remain to be elucidated, not only illustrate the unanticipated biosynthetic potential ofS. ambofaciens, but have interest in immuno-PET imaging applications.

Importance

Iron-chelating siderophores play important roles for their bacterial producers in the environment, but they have also found application in human medicine both in iron chelation therapy to prevent iron overload, as well as in advanced imaging applications. In this study we report the discovery of three novel series of related siderophores, whose biosynthesis depends on the interplay between two NRPS-independent (NIS) pathways in the producing organismS. ambofaciens– the first example to our knowledge of such functional cross-talk. We further reveal that two of these series correspond to acyl-desferrioxamines which incorporate four or five hydroxamate units. Although the biological importance of these novel derivatives is unknown, the increased chelating capacity of these metabolites may find utility in diagnostic imaging (for instance89Zr based immuno-PET imaging) and other applications of metal chelators.
Evaluating cytotoxicity and genotoxicity of oil extracted from visceral fat ofCaiman yacare(Daudin, 1802) in chinese hamster lung fibroblastin vitro
Authors: Azevedo Lucas P. , Rios-Santos Fabricio , Branco Carmen L. B. , Pressinotti Leandro N. , de M. Reis Érica , Filho Samuel V. , de O. Martins Domingos T. , de Arruda Silva Willian , de Vasconcelos Leonardo G. , Santos Ferraz Rosa Helena dos , Mesquita Fernanda Vieira , Junior Paulo T. S.
Published: July 2023

In previous studies, the oil extracted from the visceral fat ofCaiman yacare(Daudin, 1802) demonstrated a wound-healing effect on the skin of Wistar rats. To enhance knowledge our about the mechanism underlying this effect, we analysed the oil’s toxicological potentialin vitro. Cytotoxicity, genotoxicity, pro-oxidant, and antioxidant activities were evaluated in a V79-4 cell line. The oil was obtained using the Soxhlet method, and the proportions of the fatty acid profile was previously identified 43.74 % saturated and 34.65 % unsaturated fatty acids. Protocol 487 of the Organisation for Economic Co-operation and Development (OECD) was employed for cell line selection and concentrations. Cytotoxicity was determined using the MTT assay and clonogenic survival. Pro-oxidant and antioxidant activities were analysed using flow cytometry. Genotoxicity was evaluated using comet and micronucleus assays. The oil did not demonstrate cytotoxicity up to a concentration of 500 µg/mL. At concentrations of 250 and 500 µg/mL, the oil exerted a protective effect against oxidative stress and showed genotoxic effects only at the highest concentration (2000 µg/mL). Like other oils of interest for human health, the oil extracted from the visceral fat ofC. yacaredemonstrated low toxicological potentialin vitro.

SUMMARY STATEMENT

The oil fromCaiman yacarevisceral fat presents low cytotoxicity and genotoxicity, highlighting its potential for therapeutic applications without adverse effects.
Distribution of carbon monoxide (CO) in several tissues from Atlantic bottlenose dolphins (Tursiops truncatus)
Authors: Tift Michael S. , Litzenberg Kerryanne , Herrmann Kayleigh M. , Cotoia Alicia T. , Jackson Olivia N. , Keenan Tiffany F. , Kezar Kristi M. , Pearson Anna B. , McLellan William A. , Pabst D. Ann
Published: July 2023

Carbon monoxide (CO) is known as “The Silent Killer” due to its toxic effect at high concentrations, leading to an impairment in oxygen storage, delivery, and use. The cytotoxicity of CO is due to its high affinity for transition metals, such as iron, where CO outcompetes oxygen for the heme binding sites on hemoproteins in the body. CO is madein vivoin most organisms as a byproduct of heme degradation via heme oxygenase enzymes. Certain species of deep-diving marine mammals with high quantities of hemoproteins in blood and skeletal muscle have naturally elevated concentrations of CO in these tissues. To date, there exist few data on extravascular tissue CO content in wild animals. This study aims to characterize CO concentrations in nine different tissues from stranded Atlantic bottlenose dolphins (Tursiops truncatus). We found three tissues (liver, skeletal muscle, and spleen) have higher CO concentrations than other tissues. In a subset of samples from animals that tested positive for dolphin morbillivirus, the CO content in their kidney and liver was lower when compared to animals that tested negative. The mean CO concentration found in every tissue from dolphins was higher than those previously reported in healthy rodents. However, the skeletal muscle CO concentrations in dolphins from this study were much lower than those of deep-diving elephant seals. These results highlight the diversity and pattern of CO found in different tissues from bottlenose dolphins and continues to show that the heme oxygenase/carbon monoxide pathway appears to be critical for air-breathing divers.
DCLRE1B/hSNM1B (Apollo) is not acutely required for human pluripotent stem cell survival
Authors: Bartke Rebecca , Hockemeyer Dirk
Published: July 2023

Telomeric DNA ends in a 3’ single stranded overhang that is implicated in the protective function of telomeres ensuring genomic stability in mammals. Telomere overhang formation relies on the coordinated interplay between DNA synthesis and exonuclease activity. DCLRE1B/hSNM1B/Apollo generates an initial resection at the newly synthesized, blunt-ended leading strand telomere. This resection is thought to be required for further nucleolytic processing at the leading strand telomere. Here, we investigated the functional relevance of Apollo in human pluripotent stem cells (hPSCs) by generating Apollo deficient cells. Leveraging CRISPR/Cas9 technology, we generated locally haploid hPSCs (loHAPs) that lack one allele of Apollo. Subsequently, we mutated the remaining Apollo allele and monitored the resultant allele spectrum over 3 weeks. Surprisingly, cells survived regardless of Apollo status. These results suggest that, in hPSCs, Apollo is not acutely essential for cellular survival.
Data-driven modeling of core gene regulatory network underlying leukemogenesis in IDH mutant AML
Authors: Katebi Ataur , Chen Xiaowen , Li Sheng , Lu Mingyang
Published: July 2023

Acute myeloid leukemia (AML) is characterized by uncontrolled proliferation of poorly differentiated myeloid cells, with a heterogenous mutational landscape. Mutations in IDH1 and IDH2 are found in 20% of the AML cases. Although much effort has been made to identify genes associated with leukemogenesis, the regulatory mechanism of AML state transition is still not fully understood. To alleviate this issue, here we develop a new computational approach that integrates genomic data from diverse sources, including gene expression and ATAC-seq datasets, curated gene regulatory interaction databases, and mathematical modeling to establish models of context-specific core gene regulatory networks (GRNs) for a mechanistic understanding of tumorigenesis of AML with IDH mutations. The approach adopts a novel optimization procedure to identify the optimal network according to its accuracy in capturing gene expression states and its flexibility to allow sufficient control of state transitions. From GRN modeling, we identify key regulators associated with the function of IDH mutations, such as DNA methyltransferase DNMT1, and network destabilizers, such as E2F1. The constructed core regulatory network and outcomes of in-silico network perturbations are supported by survival data from AML patients. We expect that the combined bioinformatics and systems-biology modeling approach will be generally applicable to elucidate the gene regulation of disease progression.

Significance

A combined bioinformatics and systems-biology modeling approach is designed to model a transcriptional regulatory network for AML with IDH mutations. Network modeling identifies key regulators DNMT1 and E2F1, which is supported by patient survival data.
microRNA-22 displaces ITAFs from the 5’UTR and inhibit the translation of Coxsackievirus B3 RNA
Authors: Rani Priya , George Biju , Sabarishree V , Biswas Somarghya , Rajmani Raju S , Pal Apala , Das Saumitra
Published: July 2023

microRNAs play an essential role in gene regulation during virus infections and have major consequences on viral pathogenesis. During RNA virus infections, the host miRNAs can target both host mRNAs and the virus genomic RNA. Using the CVB3 virus as a model, we have investigated how a host miRNA can target viral genomic RNA and act as an antiviral factor limiting the growth of the virus. CVB3 is an RNA virus whose infection causes myocarditis and, eventually, dilated cardiomyopathy. We shortlisted miRNAs with a potential binding site in the CVB3 genomic RNA. Among these, miR-22 was picked for further studies as its binding site was putatively located in a region in the CVB3 5’ UTR, important for recruiting ITAFs and ribosomes for IRES-mediated translation. Using mutational analysis and pull-down assays, we first confirmed the binding of miR-22 on the 5’UTR. This binding negatively regulated the translation of CVB3 RNA. However, miR-22 binding-defective mutant of CVB3 RNA had no effect of miR-22 overexpression and could translate normally. Moreover, cells from which miR-22 was knocked out, showed a higher level of CVB3 infection as compared to the wild type. We have further demonstrated that the binding of miR-22 interferes with the recruitment of several ITAFs (La, PSF, and PTB) on viral mRNA. This abrogates the spatial structure necessary for ribosome recruitment on the CVB3 RNA, ultimately inhibiting its translation. Also, the level of miR-22 increases 4 hours post-infection, presumably after the synthesis of viral 2A protease, to regulate infection in the host cell more effectively. Along with the direct effect on viral RNA, the altered level of miR-22 affects the level of its cellular targets which might contribute to CVB3 infection. To identify the possible players, we obtained a list of miR-22 targets and performed pathway analysis. Several targets were shortlisted among the top hits and their levels upon CVB3 infection were checked. Protocadherin-1 (PCDH-1), a single-pass transmembrane protein, followed an expected trend, and its levels were significantly downregulated upon CVB3 infection in miR-22 dependent manner. miR-22 mediated suppression of PCDH1 levels during CVB3 infection points towards the possible role of miR-22 in either modulating antiviral signaling or in virus entry, in addition to regulating the viral translation.
STING/RANTES Pathway in Airway Epithelium Stimulates Sensitization toDer p1in an Asthma Model
Authors: Tsuji Mayoko , Kondo Mitsuko , Nishiyama Akira , Tamura Tomohiko , Nakamura-Ishizu Ayako , Tagaya Etsuko
Published: July 2023

Background

Asthma development can be attributed to various factors, including viral infections. Several pathogen including viruses activate stimulators of interferon genes (STING), and a small amount of STING agonist functions as adjuvants for sensitization to house dust mite (HDM); however, the associated mechanism is unclear. We investigated the role of STING during sensitization to HDM in airway epithelial cells.

Methods

Airway epithelial cell STING expression was analyzed using the GEO database. We delivered cyclic-GMP-AMP (cGAMP), a STING agonist to mice intranasally, and sorted epithelial cells and performed RNA-seq. Human airway epithelial cells (HBEpCs) were stimulated using cGAMPin vitro. Next, we sensitized mice with cGAMP and HDM,Der p1on Day 1, and challenged with HDM on Day 7, and on Day 8, analyzed cytokine/chemokine levels, bronchoalveolar lavage cell fraction, histology, and the number of group 2 innate lymphoid cells (ILC2s) and dendritic cells (DCs). Furthermore, we evaluated the effect of RANTES/CCL5 alone on sensitizing to HDM.

Results

Relative to other pattern recognition receptors,TMEM173, encoding STING, was highly expressed in HBEpCs, andRANTESexpression was remarkably upregulated in cGAMP-treated mice.RANTES, notIL-33orTSLP, was also activated by cGAMP in HBEpCs, especially in the presence of H2O2. Type 2 cytokine/chemokine, eosinophil, and goblet cell metaplasia increased with ILC2 and cDC2 accumulation in cGAMP-adjuvanted HDM-sensitized mice. RANTES alone functioned as an adjuvant for induction of type 2 inflammation in mice.

Conclusion

STING was highly expressed in airway epithelial cells. STING/RANTES axis may be a crucial pathway for stimulating asthma sensitization.
Nutrient deprivation differentially affects gene expression, immunity, and pathogen susceptibility across symbiotic states in a model cnidarian
Authors: Valadez-Ingersoll Maria , Aguirre Carrión Pablo J. , Bodnar Caoimhe A. , Desai Niharika A. , Gilmore Thomas D. , Davies Sarah W.
Published: July 2023

Mutualistic symbioses between cnidarians and photosynthetic algae are modulated by complex interactions between host immunity and environmental conditions. Here, we investigate how symbiosis interacts with nutrient limitation to influence gene expression and stress response programming in the sea anemoneExaiptasia pallida(Aiptasia). Transcriptomic responses to starvation were similar between symbiotic and aposymbiotic Aiptasia; however, aposymbiotic anemone responses were stronger. Starved Aiptasia of both symbiotic states exhibited increased protein levels of immune-related transcription factor NF-κB, its associated gene pathways, and putative target genes. However, this starvation-induced increase in NF-κB only correlated with increased immunity in symbiotic anemones. Furthermore, starvation had opposite effects on Aiptasia susceptibility to pathogen and oxidative stress challenges, suggesting distinct energetic priorities under nutrient scarce conditions. Finally, when we compared starvation responses in Aiptasia to those of a facultative coral and nonsymbiotic anemone, “defense” responses were similarly regulated in Aiptasia and the facultative coral, but not in the nonsymbiotic anemone. This pattern suggests that capacity for symbiosis influences immune responses in cnidarians. In summary, expression of certain immune pathways – including NF-κB – does not necessarily predict susceptibility to pathogens, highlighting the complexities of cnidarian immunity and the influence of symbiosis under varying energetic demands.
Large-FOV 3D localization microscopy by spatially variant point spread function generation
Authors: Xiao Dafei , Kedem Orange Reut , Opatovski Nadav , Parizat Amit , Nehme Elias , Alalouf Onit , Shechtman Yoav
Published: July 2023

Accurate characterization of the microscopic point spread function (PSF) is crucial for achieving high-performance localization microscopy (LM). Traditionally, LM assumes a spatially-invariant PSF to simplify the modeling of the imaging system. However, for large fields of view (FOV) imaging, it becomes important to account for the spatially variant nature of the PSF. In this work, we propose an accurate and fast principal component analysis (PCA)-based field-dependent 3D PSF generator (PPG3D) and localizer for LM. Through simulations and experimental 3D single molecule localization microscopy (SMLM), we demonstrate the effectiveness of PPG3D, enabling super-resolution imaging of mitochondria and microtubules with high fidelity over a large FOV. A comparison of PPG3D with three other shift-invariant and shift-variant PSF generators for 3D LM reveals a three-fold improvement in accuracy and an operation speed approximately one hundred times faster. Given its user-friendliness and conciseness, we believe that PPG3D holds great potential for widespread application in SMLM and other imaging modalities.
Cell membranes sustain phospholipid imbalance via cholesterol asymmetry
Authors: Doktorova Milka , Symons Jessica L. , Zhang Xiaoxuan , Wang Hong-Yin , Schlegel Jan , Lorent Joseph H. , Heberle Frederick A. , Sezgin Erdinc , Lyman Edward , Levental Kandice R. , Levental Ilya
Published: July 2023

Membranes are molecular interfaces that compartmentalize cells to control the flow of nutrients and information. These functions are facilitated by diverse collections of lipids, nearly all of which are distributed asymmetrically between the two bilayer leaflets. Most models of biomembrane structure and function often include the implicit assumption that these leaflets have similar abundances of phospholipids. Here, we show that this assumption is generally invalid and investigate the consequences of lipid abundance imbalances in mammalian plasma membranes (PM). Using quantitative lipidomics, we discovered that cytoplasmic leaflets of human erythrocyte membranes have >50% overabundance of phospholipids compared to exoplasmic leaflets. This imbalance is enabled by an asymmetric interleaflet distribution of cholesterol, which regulates cellular cholesterol homeostasis. These features produce unique functional characteristics, including low PM permeability and resting tension in the cytoplasmic leaflet that regulates protein localization. These largely overlooked aspects of membrane asymmetry represent an evolution of classic paradigms of biomembrane structure and physiology.
Veni, vidi, vici? Future spread and ecological impacts of a rapidly-expanding invasive predator population
Authors: David Nelsen R. , Aaron Corbit G. , Angela Chuang , John Deitsch F. , Michael Sitvarin I. , David Coyle R.
Published: July 2023

Economic and ecological consequences of invasive species make biological invasions an influential driver of global change. Monitoring the spread and impacts of non-native species is essential, but often difficult, especially during the initial stages of invasion. The Joro spider,Trichonephila clavata(L. Koch, 1878, Araneae: Araneidae), is a large-bodied orb weaver native to Asia, likely introduced to northern Georgia, U.S. around 2010. We investigated the nascent invasion ofT. clavataby constructing species distribution models (SDMs) from crowdsourced data to compare the climateT. clavataexperiences in its native range to its introduced range. We found evidence that the climate ofT. clavata’s native range differs significantly from its introduced range and that the most similar climate in North America to its native range is to the north of its current introduced range. We then compared the SDM predictions to current observations of spread. Consistent with predictions,T. clavataappears to be spreading faster to the north than to the south. Lastly, we conducted surveys to investigate potential ecological impacts ofT. clavataon the diversity of native orb weaving spiders. Importantly,Trichonephila clavatawas the most common and abundant species observed in the survey, and was numerically dominant at half of the sites it was present in. Our models also suggest that there is lower native orb weaver species richness and diversity closer to whereT. clavatawas initially found and where it has been established the longest, though human population density complicates this finding. This early study is the first to forecast how widely this spider may spread in its introduced range and explore potential ecological impacts ofT. clavata, and we call for continued investigation of this invasion’s effects.
Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn
Authors: Liebhoff Anna-Maria , Venkataraman Thiagarajan , Morgenlander William R , Na Miso , Kula Tomasz , Waugh Kathleen , Morrison Charles , Rewers Marian , Longman Randy , Round June , Elledge Stephen , Ruczinski Ingo , Langmead Ben , Larman H Benjamin
Published: July 2023

We investigated a relatively underexplored component of the gut-immune axis by profiling the antibody response to gut phages using Phage Immunoprecipitation Sequencing (PhIP-Seq). To enhance this approach, we developed Dolphyn, a novel method that uses machine learning to select peptides from protein sets and compresses the proteome through epitope-stitching. Dolphyn improves the fraction of gut phage library peptides bound by antibodies from 10% to 31% in healthy individuals, while also reducing the number of synthesized peptides by 78%. In our study on gut phages, we discovered that the immune system develops antibodies to bacteria-infecting viruses in the human gut, particularlyE.coli-infectingMyoviridae. Cost-effective PhIP-Seq libraries designed with Dolphyn enable the assessment of a wider range of proteins in a single experiment, thus facilitating the study of the gut-immune axis.
Smith-Magenis syndrome protein RAI1 regulates body weight homeostasis through hypothalamic BDNF-producing neurons and neurotrophin downstream signalling
Authors: Javed Sehrish , Chang Ya-Ting , Cho Yoobin , Lee Yu-Ju , Chang Hao-Cheng , Haque Minza , Lin Yu Cheng , Huang Wei-Hsiang
Published: July 2023

Retinoic acid-induced 1(RAI1) haploinsufficiency causes Smith-Magenis syndrome (SMS), a genetic disorder with symptoms including hyperphagia, hyperlipidemia, severe obesity, and autism phenotypes. RAI1 is a transcriptional regulator with a pan-neural expression pattern and hundreds of downstream targets. The mechanisms linking neuralRai1to body weight regulation remain unclear. Here we find that hypothalamic brain-derived neurotrophic factor (BDNF) and its downstream signalling are disrupted in SMS (Rai1+/-) mice. SelectiveRai1loss from all BDNF-producing cells or from BDNF-producing neurons in the paraventricular nucleus of the hypothalamus (PVH) induced obesity in mice. Electrophysiological recordings revealed thatRai1ablation decreased the intrinsic excitability of PVHBDNFneurons. Chronic treatment of SMS mice with LM22A-4 engages neurotrophin downstream signalling and delayed obesity onset. This treatment also partially rescued disrupted lipid profiles, insulin intolerance, and stereotypical repetitive behaviour in SMS mice. These data argue that RAI1 regulates body weight and metabolic function through hypothalamic BDNF-producing neurons and that targeting neurotrophin downstream signalling might improve associated SMS phenotypes.
Genetic reprogramming by brief inhibition of the renin-angiotensin system in spontaneously hypertensive rats leads to persistently reduced kidney renin and low blood pressure
Authors: Byars Sean G. , Prestes Priscilla , Suphapimol Vara , Takeuchi Fumihiko , De Vries Nathan , Maier Michelle C , Melo Mariana , Balding David , Samani Nilesh , Allen Andrew , Kato Norihiro , Wilkinson-Berka Jennifer L , Charchar Fadi , Harrap Stephen B
Published: July 2023

BACKGROUND

Prevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this reprogramming, but relevant genetic changes are unknown.

METHODS

In SHR, we studied the effect of treatment between 10 and 14 weeks of age with the angiotensin receptor blocker, losartan, or the angiotensin-converting enzyme (ACE) inhibitor, perindopril (with controls for non-specific effects of lowering BP) on differential RNA expression, DNA methylation and renin immunolabelling in the kidney at 20 weeks of age.

RESULTS

RNA sequencing revealed a 6-fold increase in renin gene (Ren) expression during losartan treatment (P < 0.0001). At 20 weeks, six weeks after treatment cessation, mean arterial pressure remained lower in the treated SHR (P = 0.006), kidneyRenexpression was reduced by 23% (P = 0.03) and DNA methylation within theRenpromoter region was increased (P = 0.04). Experiments with the ACE inhibitor perindopril confirmed a long-term reduction in kidneyRenexpression of 43% (P = 1.4 x 10-6). Renin immunolabelling was also lower after losartan or perindopril treatment (P = 0.002). RNA sequencing identified differential expression of 13 candidate genes (Grhl1,Ammecr1l,Hs6st1,Nfil3,Fam221a,Lmo4,Adamts1,Cish,Hif3a,Bcl6,Rad54l2,Adap1,Dok4) and the miRNA miR-145-3p. We found correlations between expression of mRNAs, miRNAs and lncRNAs that we believe represent genetic networks underpinning the decreasedRenexpression and lower BP. Gene ontogeny analyses revealed that these networks were enriched with genes relevant to BP, RAS and the kidneys.

CONCLUSIONS

Early RAS inhibition in SHR reprograms genetic pathways and networks resulting in a legacy of reducedRenexpression and the persistent reduction in BP.
Long-chain fatty acyl-coenzyme A activates the mitochondrial fission factors MiD49 and MiD51 by inducing their oligomerization
Authors: Liu Ao , Kage Frieda , Sapp Gracie , Aydin Halil , Higgs Henry N.
Published: July 2023

Mitochondrial fission occurs in many cellular processes, but the regulation of fission is poorly understood. We show that long-chain acyl coenzyme A (LCACA) activates two related mitochondrial fission proteins, MiD49 and MiD51, by inducing their oligomerization, activating their ability to stimulate DRP1 GTPase activity. The 1:1 stoichiometry of LCACA:MiD in the oligomer suggests interaction in the previously identified nucleotide-binding pocket, and a point mutation in this pocket reduces LCACA binding and LCACA-induced oligomerization for MiD51. In cells, this LCACA binding mutant does not assemble into puncta on mitochondria or rescue MiD49/51 knock-down effects on mitochondrial length and DRP1 recruitment. Furthermore, cellular treatment with the fatty acid analogue 2-bromopalmitate, which causes increased acyl-CoA, promotes mitochondrial fission in an MiD49/51-dependent manner. These results suggest that LCACA is an endogenous ligand for MiDs, inducing mitochondrial fission and providing a potential mechanism for fatty acid-induced mitochondrial fragmentation. Finally, MiD49 or MiD51 oligomers synergize with MFF, but not with actin filaments, in DRP1 activation, suggesting distinct pathways for DRP1 activation.
Crystal structure of bis(3,5-dichloro-2-hydroxybenzyl)(2-methoxyethyl)amine
Authors: Wile Bradley M. , Griffith Claire L. , Johnson Adam R.
Published: July 2023

The title compound, systematic name 4,4′,6,6′-tetrachloro-2,2′-{[(2-methoxyethyl)azanediyl]bis(methylene)}diphenol (C17H17Cl4NO, 1), was prepared via a modified Mannich reaction between 2-methoxyethylamine, 2,4-dichlorophenol, and aqueous formaldehyde. The resulting amine bis(phenol) provides an interesting comparison to related species as a result of the electron-withdrawing substituents on the phenol rings, in combination with similar steric parameters. One of the Cl atoms was modeled as a two-component disorder with partial occupancies of 0.49 (3) and 0.51 (3), while the pendant ether group was modeled as a two-component disorder with partial occupancies of 0.867 (3) and 0.133 (3). A comparison of metrical parameters for the title compound and closely related structures provides insight into the use of these species as ligands to support transition-metal complexes for applications as homogeneous catalysts.
5,6-Dihydro-1,4-dithiine-2,3-dicarboxylic anhydride
Authors: Bullock Olivia , Rice Sarah , Bond Marcus R.
Published: July 2023

In the title compound (systematic name: 2,3-dihydro-1,4-dithiino[2,3-c]furan-5,7-dione), C6H4O3S2, the observed geometry agrees well with those of its phthalamide, thieno and hydroxy analogs, and with a calculated geometry obtained by density functional theory (DFT) calculations. Specific structural features are an S—C—C—S torsion angle of −70.39 (17)° and S—C bonds to sp
2-hybridized C atoms approximately 0.1 Å shorter than those to sp
3-hybridized C atoms. Unlike the extended structures of the analogs, there are no directed intermolecular interactions and the head-to-tail rows of molecules that are a prominent structural motif of the packing can be rationalized in terms of optimized dipole–dipole interactions.
A multi-disciplinary view on a corporate real estate alignment model
Authors: Cooke Howard , Appel-Meulenbroek Rianne
Published: July 2023

Purpose

The purpose of this paper is to examine a recent comprehensive corporate real estate (CRE) alignment model which was derived from previous CRE alignment models. This study proposes several modifications and additions based on business and decision-making literature to increase the framework’s multidisciplinary strength and extend its implementation phase.

Design/methodology/approach

Literature from various fields is reviewed and “lessons” incorporated into the framework. The business literature review began with corporate strategy theories cited in CRE alignment theory and extended to critiques of those and more recent theories. Likewise, decision-making and implementation both began with material cited in CRE literature and “rippled” out to encompass pertinent material.

Findings

The model used provides a robust framework, and this study has identified several areas that would appear to improve that model from a theoretical and practical perspective. Areas of further research are identified that appear to offer opportunities to further develop the framework.

Originality/value

Historically, there has been a tendency for new CRE alignment models to be created rather than existing ones being developed further. Here, a framework derived from a meta-study of CRE alignment models is reviewed, and improvements are proposed to further develop CRE alignment theory and its application in practice through the addition of viewpoints from the business field and more focus on the implementation phase of the model.
The mediation model of learning organization, technology acceptance and service innovation: Part I
Authors: Kalıpçı Mehmet Bahadır
Published: July 2023

Purpose

This paper aims to create a conceptual model that connects learning organizations, service innovation and technology acceptance.

Design/methodology/approach

The importance of the interaction of variables benefiting both individuals and organizations has been comprehensively explained by combining two well-known theories – learning organizational theory and service innovation theory – with the technology acceptance model. In the first part of the study, conceptual model has been constructed and then applied to the hospitality industry of which results have been presented in the second part of this paper.

Findings

It is hypothesized that learning organization, service innovation and technology acceptance have significant relationships. It is also suggested that the learning organization plays an intermediary role in the relationship between technology acceptance and service innovation. Empirical results in this regard have been presented in the second part of the paper.

Research limitations/implications

The relations have been established and tested in the hospitality industry in Antalya. However, the model can be applied and established relations tested in other industries.

Originality/value

This research contributes to our knowledge of the intricate linkages that exist between learning organizations, technology acceptance and service innovation. Originality of the paper is related to the novel multilayered model illustrating three-way interactions between the three dimensions of learning organization, technology acceptance and service innovation.
Functional traits of both specific alien species and receptive community but not community diversity determined the invasion success under biotic and abiotic conditions
Authors: Hou Meng , Wang Jianyong
Published: July 2023

Biodiversity can provide some resistance to alien species in some cases, but not in others. The observed paradoxical results may be related to several reasons, including variations in abiotic and/or biotic conditions, alien species characteristics and the fact that the species number cannot adequately reflect native community diversity. A comprehensive study that incorporates these elements is lacking.

We constructed invasion systems using nine alien plant species and 12 native communities, composed of two diversity levels (three vs. six species), under different nitrogen (N) and arbuscular mycorrhiza fungi (AMF) inoculation conditions. We used this fully crossed factorial experiment, that is, N (low vs. high) × native community diversity (three vs. six species) × AMF (with vs. without), to systematically explore the invasion success in native communities.

We found that the species number of native community did not affect invasion success under any of the N or AMF conditions. The effects of N enrichment and AMF inoculation on invasion were not consistent between alien species and native communities based on their phenotypic plasticity of functional traits in response to N enrichment and AMF inoculation. Specifically, the changing of invasion in response to N enrichment and AMF inoculation was associated with the plasticity of plant height and root mass fraction that reflects the competitiveness for the acquisition of light and soil resources.

Our results that species number did not capture well the resistance of the native community suggested that the simple expression of species richness is not realistic to describe the invasion resistance of the community. Additionally, the association between functional traits of both alien species and native communities and invasion success suggested that changes in competitive advantage and resource acquisition strategy are more important in explaining changes in invasive success in different N and AMF conditions.

Future studies are needed to explore invasion success by systematically considering the characteristics of invasive species and the native community, and the specific abiotic and biotic conditions. Using functional traits may help advance our understanding of plant invasion in broad circumstances and shed light on a generalized framework of biological invasion.

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‘About the Tangle of the Rose’: Thinking with the Fin‐de‐Siècle Tendril
Authors: Cox Emily
Published: July 2023

‘[It] transported me a thousand miles from London, to a thousand years from the age of Mr. Gladstone’, recalled Robert de la Sizeranne of Edward Burne‐Jones's Briar Rose series (1884–90). This essay argues, on the contrary, that the paintings were closer to contemporary concerns than Sizeranne allowed. In Burne‐Jones's briar, we find a remarkable example of one of the late nineteenth century's most promiscuous and ambiguous motifs: the tendril. Perhaps unexpectedly, this ornamental motif was at the centre of fin‐de‐siècle debates about time, capitalist expansion, and imperialism. In visual art, philosophy, and art history, the tendril figured anxieties about where Europe was heading. Tracing its movement through Burne‐Jones's canvases into texts by Henri Bergson and Alois Riegl, and decorative art by Victor Horta and William Morris, this essay contends that the tendril traverses a shared, but fragile, trans‐European imperial landscape at the end of the nineteenth century.
Home‐schooling in the Republic of Ireland
Authors: Banks Joanne , Forlin Chris , Chambers Dianne
Published: July 2023

Internationally, there continues to be a rise in the popularity of home‐schooling. Although the growth in the numbers of families choosing this alternative approach was evident prior to the Covid‐19 Pandemic school closures, it appears to have impacted on the decision for some to home‐school permanently. Using a scoping review of the literature, this paper considers the research evidence around home‐schooling in the United Kingdom and Europe. It then focuses on home‐schooling in the Republic of Ireland to assess the change and development of home‐schooling over time. In line with trends internationally, Irish administrative data show an increase in the numbers of families engaging in home‐schooling in recent years, particularly for students with disabilities. The paper situates these findings within the context of ongoing debates on inclusive and special education in Ireland and the capacity of mainstream schools to educate and include every student.
Balancing conservation and welfare in ex situ management of the extinct‐in‐the‐wild sihek: sex‐ and age‐specific causes of mortality and contributions to population growth rate
Authors: Trask A. E. , Carraro C. , Kock R. , McCrea R. , Newland S. , Royer E. , Medina S. , Fontenot D. , Ewen J. G.
Published: July 2023

Ex situ threatened species management has both conservation and welfare objectives and these objectives often align, but can diverge. Areas of agreement can present win‐wins for achieving welfare and conservation objectives, while identifying areas of divergence is important to ensure management strategies achieve balance across objectives. We examined welfare and conservation objectives in the ex situ population of Extinct in the Wild sihek (Guam kingfisher, Todiramphus cinnamominus) by quantifying mortality rates, determining sex‐ and age‐specific causes of mortality and identifying associated welfare domains, as well as quantifying sex‐ and age‐specific differences in reproductive value and contributions to variation in population growth rate (λ). Females had significantly higher mortality rates than males, potentially impacting population viability and suggesting females may be more vulnerable to experiencing lower welfare than males. Mitigating causes of female mortality would therefore present a clear win‐win for both welfare and conservation objectives. Both causes of mortality and contributions to variation in λ were found to differ across sex‐ and age‐classes. In particular, nutritional and metabolic diseases tended to impact younger age‐classes and these age‐classes had large contributions to variation in λ. Mitigation of these diseases could therefore also present a win‐win for welfare and conservation objectives. However, we also identified a potential divergence between objectives: a major cause of female mortality was reproductive disease with older aged females primarily affected, but older aged females contributed little to variation in λ and had low reproductive value. Developing mitigation strategies for reproductive disease could therefore aid welfare objectives but have little benefit for conservation objectives, suggesting careful balancing across objectives is required. Our results highlight the need to explicitly consider conservation and welfare objectives in threatened species management, in particular in the context of an increasing conservation need for ex situ population management, coupled with increasing social concern for animal welfare.
Economic and cost considerations of delivering and using mobile X‐ray services in residential aged care facilities: A qualitative study
Authors: Dollard Joanne , Edwards Jane , Yadav Lalit , Gaget Virginie , Tivey David , Inacio Maria C. , Maddern Guy J. , Visvanathan Renuka
Published: July 2023

Objective

To describe the economic and cost considerations of mobile X‐ray services (MXS) in residential aged care facilities (RACFs), according to stakeholders (involved in residents' healthcare), residents living in RACFs and informal carers (ICs) of residents.

Methods

Semistructured interviews were conducted with 20 residents and 27 ICs recruited from six RACFs across metropolitan Adelaide (South Australia, Australia), and 22 stakeholders, on their perspectives of using MXS in RACFs. Data relating to economic and cost considerations were extracted and analysed using thematic analysis.

Results

Residents' mean age was 85 years, 60% were women and 40% had experienced an MXS in the last 12 months. Most ICs were daughters (70%) and wives (11%) and 30% had a family member who had experienced an MXS in the last 12 months. Stakeholders included RACF staff, GPs, a hospital avoidance program clinician, paramedics, emergency department clinicians, MXS radiographers and manager, and a radiologist. Four themes were presented: (1) business considerations, where private providers found it necessary to charge residents a co‐payment to deliver MXS; (2) cost and payment process as a potential barrier to using MXS, with varied willingness and ability to pay for an MXS co‐payment, and equity concerns; (3) overcoming cost and payment barriers, with staff and consumers sometimes using strategies to overcome cost barriers; and (4) perceived cost benefits of MXS to the healthcare system, residents and ICs.

Conclusions

Mobile X‐ray services providers charge residents an upfront co‐payment for business viability, which can be a barrier to some residents wishing to access MXS.
The State of Uberisation: Neoliberalism, Smart Urbanism, and the Regulated Deregulation of Toronto's Taxi‐cum‐Ridehail Market
Authors: Namberger Fabian
Published: July 2023

In 2016, the City of Toronto legalised the ridehail giant Uber under a particularly Uber‐friendly regulatory regime. Rather than understanding this interim outcome along the lines of now widespread narratives of corporate “disruption”, in this article I take up Manuel B. Aalbers’ notion of “regulated deregulation” in order to foreground the state's role as a manically prolific facilitator of early Uberisation. Based on ethnographic research in Toronto, I argue that the three longer‐standing state spatial strategies of (1) the common‐sense neoliberal state, (2) the labour‐averse competition state, and (3) the tech‐infatuated smart state were paramount in creating those “on‐the‐ground” conditions—social, legal, spatial, and other—on which Uber has been able to thrive in many cities across the North American continent.
FISH‐ing for answers: Can genomic arrays add to our understanding of disease biology in low‐risk chronic lymphocytic leukaemia?
Authors: Rhodes Joanna
Published: July 2023

Patients with chronic lymphocytic leukaemia can have an indolent or aggressive clinical course. Current guidelines recommend performing immunoglobin heavy chain testing, four‐colour probe fluorescence in situ hybridization testing and mutational analysis for TP53 mutations as part of routine prognostic testing to determine if high‐risk genomic features are present. Rigolin et al. demonstrate that genomic microarray testing can identify high‐risk genomic features in patients deemed low risk by current testing standards and is independently associated with shorter time to first treatment in their cohort.

Commentary on: Rigolin et al. Additional lesions identified by genomic microarrays are associated with an inferior outcome in low‐risk chronic lymphocytic leukaemia patients. Br J Haematol 2023;202:953–959.