bluuebunny/crossref_metadata_2025 huggingface dataset:
“Are We Working (Too) Comfortably?”: Understanding the Nature of and Factors Associated with Sedentary Behaviour When Working in the Home Environment
Authors: Niven Ailsa , Baker Graham , Almeida Eva Coral , Fawkner Samantha G , Jepson Ruth , Manner Jillian , Morton Sarah , Nightingale Glenna , Sivaramakrishnan Divya , Fitzsimons Claire
Published: November 2022

Home working has increased due to COVID-19, but little is known about how this change has impacted the health risk behaviour of elevated sedentary time. The aim of this cross-sectional exploratory study was to assess occupational sitting behaviour when working at home, and use the Capability Opportunity Motivation-Behaviour (COM-B) model to identify influences on this behaviour. University staff (n = 267; 69% female; 92% white) who were predominantly working from home completed a questionnaire to assess sitting time, sitting breaks, demographic and occupational characteristics, and a 7-item COM-B questionnaire and open-ended questions to assess influences on time spent sitting whilst working from home. Data were analysed descriptively, a repeated measures ANOVA was used to determine differences in the COM-B items, and binary logistic regression was used to examine predictors of sitting time. Staff spent on average 89.5% (SD = 17.1) of their time sitting whilst working at home, and took an average of 1.36 (1.38) sitting breaks per hour. There were significant and meaningful differences in the influence of the COM factors on ability and willingness to reduce sitting behaviour (p < .0001; ηp2 = .38), and the open-ended responses added further context. The included variables accounted for 20.7% of variance in sitting behaviour, with age, sitting breaks, motivation-automatic, and opportunity-physical contributing significantly. Working from home leads to elevated levels of sitting, and the COM-B provides a useful model to identify key influences on ability and willingness to reduce sitting. Strategies incorporating regular breaks, habit formation/reversal, and restructuring the physical environment may be beneficial.
Making sense of the crisis: how religion shapes the attribution of meaning during the corona pandemic
Authors: Unser Alexander , Riegel Ulrich
Published: November 2022

In times of existential crisis, such as the Corona pandemic, people may turn to religious traditions that help them make new sense of the depressing situation. While recent studies have shown that during the Corona pandemic, the frequency of prayer and church attendance increased in several countries, we know little about whether and how religious interpretations of the current crisis occur. Building on Crystal Park’s Meaning Making Model, the article examines whether individual religiosity, religious affiliation, and the experience of a SARS-CoV‑2 infection influence religious interpretations of the Corona pandemic. Our results show that religiosity is strongly associated with the idea of a benevolent God and weakly associated with the concept of a punishing God. Members of specific religious groups differed significantly in their religious interpretation of the Corona pandemic. Finally, we found that the experience of a SARS-CoV‑2 infection was associated with doubts about the power of God.
Controlling Lattice Misfit and Creep Rate Through the γ' Cube Shapes in the Al10Co25Cr8Fe15Ni36Ti6 Compositionally Complex Alloy with Hf and W Additions
Authors: Yesilcicek Y. , Haas S. , Suárez Ocaño P. , Zaiser E. , Hesse R. , Többens D. M. , Glatzel U. , Manzoni A. M.
Published: November 2022

Trace elements play an important role in the fine-tuning of complex material properties. This study focuses on the correlation of microstructure, lattice misfit and creep properties. The compositionally complex alloy Al10Co25Cr8Fe15Ni36Ti6 (in at. %) was tuned with high melting trace elements Hf and W. The microstructure consists of a γ matrix, γ' precipitates and the Heusler phase and it is accompanied by good mechanical properties for high temperature applications. The addition of 0.5 at.% Hf to the Al10Co25Cr8Fe15Ni36Ti6 alloy resulted in more sharp-edged cubic γ′ precipitates and an increase in the Heusler phase amount. The addition of 1 at.% W led to more rounded γ′ precipitates and the dissolution of the Heusler phase. The shapes of the γ' precipitates of the alloys Al9.25Co25Cr8Fe15Ni36Ti6Hf0.25W0.5 and Al9.25Co25Cr8Fe15Ni36Ti6Hf0.5W0.25, that are the alloys of interest in this paper, create a transition from the well-rounded precipitates in the alloy with 1% W containing alloy to the sharp angular particles in the alloy with 0.5% Hf. While the lattice misfit has a direct correlation to the γ' precipitates shape, the creep rate is also related to the amount of the Heusler phase. The lattice misfit increases with decreasing corner radius of the γ' precipitates. So does the creep rate, but it also increases with the amount of Heusler phase. The microstructures were investigated by SEM and TEM, the lattice misfit was calculated from the lattice parameters obtained by synchrotron radiation measurements.
Modelling falling film flow: an adjustable formulation
Authors: Mukhopadhyay Sanghasri , Ruyer-Quil Christian , Usha R.
Published: November 2022

A new two-equation model for gravity-driven liquid film flow based on the long-wave expansion has been derived. The novelty of the model consists in using a base velocity profile combining parabolic (Ruyer-Quil & Manneville, Eur. Phys. J. B, vol. 15, issue 2, 2000, pp. 357–369) and ellipse (Usha et al., Phys. Fluids, vol. 32, issue 1, 2020, 013603) profile functions in the wall-normal coordinate. The dependence on a free parameter

$A$

related to the eccentricity of an ellipse serves as an adjustable parameter. The resulting models are consistent at

$O(\varepsilon )$

for inertia terms and at

$O(\varepsilon ^2)$

for viscous diffusion effects, and predict accurately the primary instability. Appropriate tuning of the adjustable parameter helps to recover accurate predictions for the asymptotic wave celerity of nonlinear solitary waves. Further, the model is shown to capture the closed separation vortices that can form underneath the troughs of precursory capillary ripples.
Use of peripheral blood eosinophils to guide post-operative glucocorticoid therapy in patients with chronic rhinosinusitis with nasal polyps: a randomised, controlled trial
Authors: Liu Y , Xing Z , Geng C , Liu Y , Cao J , Yang Y , Pan T , Yu L
Published: November 2022

Objective

This study aimed to explore the utility of the eosinophil percentage in peripheral blood for guiding post-operative glucocorticoid therapy in patients with chronic rhinosinusitis with nasal polyps.

Methods

Forty-four patients with chronic rhinosinusitis with nasal polyps underwent functional endoscopic sinus surgery and were randomly divided into two groups. Patients in the standard treatment group used oral and nasal spray glucocorticoids. In the biomarker treatment group, patients with peripheral blood eosinophil percentage values less than 3.05 per cent did not receive glucocorticoid treatment, whereas patients with values 3.05 per cent or above were part of the standard treatment group. Visual Analogue Scale, Sino-Nasal Outcome Test-22 scores, endoscopic Lund–Kennedy scores, eosinophils, interleukin-5 and eosinophil cationic protein in peripheral blood, and nasal secretions were measured.

Results

After functional endoscopic sinus surgery, the Visual Analogue Scale, Sino-Nasal Outcome Test-22 and Lund–Kennedy scores were significantly reduced in both groups; there were no significant differences in those indicators between the groups during the three follow-up visits.

Conclusion

Peripheral blood eosinophil percentage offers a potential biomarker to guide post-operative glucocorticoid therapy in patients with chronic rhinosinusitis with nasal polyps.
Adaptions of photosynthesis in sun and shade in populations of some Afromontane lichens
Authors: Mkhize Kwanele Goodman Wandile , Minibayeva Farida , Beckett Richard Peter
Published: November 2022

Photosynthetic organisms have evolved a great variety of mechanisms to optimize their use of sunlight. Some of the clearest examples of adaptations can be seen by comparing photosynthesis in different species and in different individuals of the same species that grow under high and low light levels. While the adaptations of sun and shade higher plants have been relatively well studied, much less information is available on the photobionts of lichenized Ascomycetes. An important adaptation that can protect photosynthetic organisms from the potentially harmful effects of excess light is non-photochemical quenching (NPQ); NPQ can dissipate unused light energy as heat. Here we used chlorophyll fluorescence to compare the induction and relaxation of NPQ and the induction of electron transport (rETR) in collections of the same lichen species from exposed and from more shaded locations. All species have trebouxioid photobionts and normally grow in more exposed microhabitats but can also be readily collected from more shaded locations. Shade forms display generally higher NPQ, presumably to protect lichens from occasional rapid increases in light that occur during sunflecks. Furthermore, the NPQ of shade forms relaxes quickly when light levels are reduced, presumably to ensure efficient photosynthesis after a sunfleck has passed. The maximal relative electron transport rate is lower in shade than sun collections, probably reflecting a downregulation of photosynthetic capacity to reduce energy costs. We also compared collections of pale and melanized thalli from three species of shade lichens with Symbiochloris as their photobiont. Interestingly, NPQ in melanized thalli from slightly more exposed microhabitats induced and relaxed in a way that resembled shade rather than sun forms of the trebouxioid lichens. This might suggest that in some locations melanization induced during a temporary period of high light may be excessive and could potentially reduce photosynthesis later in the growing season. Taken together, the results suggest that lichen photobionts can flexibly adjust the amount and type of NPQ, and their levels of rETR in response to light availability.
Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden
Authors: Nichter Brandon , Koller Dora , De Angelis Flavio , Wang Jiawei , Girgenti Matthew J. , Na Peter J. , Hill Melanie L. , Norman Sonya B. , Krystal John H. , Gelernter Joel , Polimanti Renato , Pietrzak Robert H.
Published: November 2022

Background

Little is known about environmental factors that may influence associations between genetic liability to suicidality and suicidal behavior.

Methods

This study examined whether a suicidality polygenic risk score (PRS) derived from a large genome-wide association study (N = 122,935) was associated with suicide attempts in a population-based sample of European-American US military veterans (N = 1664; 92.5% male), and whether cumulative lifetime trauma exposure moderated this association.

Results

Eighty-five veterans (weighted 6.3%) reported a history of suicide attempt. After adjusting for sociodemographic and psychiatric characteristics, suicidality PRS was associated with lifetime suicide attempt (odds ratio 2.65; 95% CI 1.37–5.11). A significant suicidality PRS-by-trauma exposure interaction emerged, such that veterans with higher levels of suicidality PRS and greater trauma burden had the highest probability of lifetime suicide attempt (16.6%), whereas the probability of attempts was substantially lower among those with high suicidality PRS and low trauma exposure (1.4%). The PRS-by-trauma interaction effect was enriched for genes implicated in cellular and developmental processes, and nervous system development, with variants annotated to the DAB2 and SPNS2 genes, which are implicated in inflammatory processes. Drug repurposing analyses revealed upregulation of suicide gene-sets in the context of medrysone, a drug targeting chronic inflammation, and clofibrate, a triacylglyceride level lowering agent.

Conclusion

Results suggest that genetic liability to suicidality is associated with increased risk of suicide attempt among veterans, particularly in the presence of high levels of cumulative trauma exposure. Additional research is warranted to investigate whether incorporation of genomic information may improve suicide prediction models.
Capacitating militarised masculinity: Genitourinary injuries, sex/sexuality, and US military medicine
Authors: Hobbs Jenn
Published: November 2022

This article examines the soldiering body in relation to the increasing prevalence of genitourinary injuries in military personnel. Feminist scholars have demonstrated that the idealised masculine soldiering body are central to the workings of international politics. The article shows that US militarised masculinity operates through the selective distribution of bodily capacities. The article draws upon critical disability studies, particularly Jasbir Puar's work on capacity and debility, to argue that treatments for genitourinary injuries revolve around the production of seminal capacity. Queer and trans bodies are debilitated in these arrangements through the denial of heterosexual and cisgender capabilities to them. To unpack this argument the article analyses treatments for genitourinary injuries. The article shows that genitourinary injuries destabilise the gender identity of US service members. Through an exploration of surgical treatments, including penis transplants and reconstructive surgeries, and fertility treatments, the article shows how masculine capacitation is achieved for some US service members through the debilitation of others; in particular, queer and trans bodies, and the bodies of Iraqi and Afghan civilians.
Do scientific objects have a life (which may end)?
Authors: Arabatzis Theodore
Published: November 2022

Argument

The aim of this article is to make a case for the pertinence of a biographical approach to the history of scientific objects. I first lay out the rationale of that approach by revisiting and extending my earlier work on the topic. I consider the characteristics of scientific objects that motivate the biographical metaphor, and I indicate its virtues and limitations by bringing out the positive and negative analogies between biographies of scientific objects and ordinary biographies. I then point out various ways in which scientific objects may pass away and argue that their demise should be conceptualized as a process. Finally, I sketch the history of the concept of “ether” in nineteenth and early twentieth century physics and suggest that it lends itself particularly well to a biographical treatment. To that effect, I discuss the identity, heuristic character, and recalcitrance of the ether and examine the reasons that may have led to its passing.
A simple European option pricing formula with a skew Brownian motion
Authors: Pasricha Puneet , He Xin-Jiang
Published: November 2022

Zhu and He [(2018). A new closed-form formula for pricing European options under a skew Brownian motion. The European Journal of Finance 24(12): 1063–1074] provided an innovative closed-form solution by replacing the standard Brownian motion in the Black–Scholes framework using a particular skew Brownian motion. Their formula involves numerically integrating the product of the Guassian density and corresponding distribution function. Being different from their pricing formula, we derive a much simpler formula that only involves the Gaussian distribution function and Owen's $T$ function.
Special issue introduction: Contemporary international anti-feminism
Authors: Sanders Rebecca , Jenkins Laura Dudley
Published: November 2022

In recent years, conservative governments and their civil society allies have undermined international women’s rights treaties and SOGI rights initiatives and challenged domestic rights protections. The articles in this special issue grapple with these trends by analysing the ideologies, discourses, and strategies of contemporary anti-feminism in global and comparative contexts. Several prominent patterns emerge: the core significance of social hierarchy and biological essentialism to anti-feminist conservative thought; the polarizing demonization of feminists by religious conservatives and populist nationalists; the appropriation of rights discourses and advocacy tactics by anti-feminist campaigns; and the strategic importance of law and legal language as a terrain of rights contestation. Taken together, this research suggests that anti-feminism is not incidental to reactionary anti-democratic politics, but instead a constitutive element of political movements that seek to naturalize inequality and legally enforce conformity with conservative social norms.
Chasing Tails: Insights From Micromagnetic Modeling for Thermomagnetic Recording in Non‐Uniform Magnetic Structures
Authors: Nagy Lesleis , Williams Wyn , Tauxe Lisa , Muxworthy Adrian
Published: November 2022

Paleointensities are key to understanding the formation and evolution of Earth and are determined from rocks which record magnetic fields upon cooling; however, experimental protocols for estimating paleointensities frequently fail. The primary reason is that laboratory protocols assume that rocks are dominated by uniformly magnetized, single‐domain grains, instead of much more common non‐uniformly magnetized grains. Our model for larger grains shows a multiplicity of stable domain states; with preferred states changing as a function of temperature. We show that domain state distribution depends on the thermal history of the sample—in nature and the laboratory. From numerical thermomagnetic modeling, we show that particles with non‐uniform domain states will theoretically fail standard experimental paleointensity protocols, preventing us from determining reliable ancient geomagnetic field intensities. We propose that recognizing this type of behavior, and the resulting bias, will yield more reliable paleointensity records, and a better understanding of the Earth.
Glacial Isostatic Adjustment Shapes Proglacial Lakes Over Glacial Cycles
Authors: Austermann J. , Wickert A. D. , Pico T. , Kingslake J. , Callaghan K. L. , Creel R. C.
Published: November 2022

As ice sheets load Earth's surface, they produce ice‐marginal depressions which, when filled with meltwater, become proglacial lakes. We include self‐consistently evolving proglacial lakes in a glacial isostatic adjustment (GIA) model and apply it to the Laurentide ice sheet over the last glacial cycle. We find that the locations of modeled lakes and the timing of their disappearance is consistent with the geological record. Lake loads can deflect topography by >10 m, and volumes collectively approach 30–45 cm global mean sea‐level equivalent. GIA increases deglaciation‐phase lake volume up to five‐fold and average along‐ice‐margin depth ≤90 m compared to glaciation‐phase ice volume analogs—differences driven by changes in the position and size of the peripheral bulge. Since ice‐marginal lake depth affects grounding‐line outflow, GIA‐modulated proglacial lake depths could affect ice‐sheet mass loss. Indeed, we find that Laurentide ice‐margin retreat rate sometimes correlates with proglacial lake presence, indicating that proglacial lakes aid glacial collapse.
Unraveling the Synoptic‐Scale Penetration of the Yellow Sea Coastal Water Into the Changjiang River Estuary
Authors: Lian Ergang , Wang Shuo , Artigue Lise , Wu Hui , Ran Xiangbin , Zhou Peng , Lin Lei , Jin Xiaobo , Li Chao , Yang Shouye
Published: November 2022

As one of the most important coastal currents in the Northeast Pacific marginal seas, the Yellow Sea Coastal Water (YSCW) plays an essential role in modulating regional ocean circulation and the transregional exchange of biogeochemical materials. However, the wintertime transport pattern of the YSCW and its interaction with the Changjiang River Estuary (CJE) are intensely debated. Herein, we used a combination method of Principal Component Analysis‐based cluster analysis and Optimum Multiparameter Analysis, together with remote sensing data, to investigate the classification, distributions, pathways and mixture ratios of various water masses off the CJE in winter. Results clearly suggest that in winter the YSCW can repeatedly penetrate to the CJE in response to northerly wind bursts, and flows southward around 10–30 m isobaths off the CJE, with its impact scope reaching as far as at least 29.5°N. Furthermore, we propose a refined circulation pattern that the YSCW flows southward along 20–30 m isobaths on the Changjiang Bank, and thereby feeds the synoptic‐scale YSCW penetration into the CJE. Crucially, this work also highlights that the combination methodologies in a mathematic framework is useful for unraveling an implicit synoptic‐scale water mass interaction in highly dynamic estuaries and shelf seas, and thus provides better insight to ecological and environmental variability.
Drought Impacts on PM2.5 Composition and Amount Over the US During 1988–2018
Authors: Wang Yi , Wang Jun , Wang Yuxuan , Li Wei
Published: November 2022

This study uses PM2.5 species concentrations from Interagency Monitoring of Protected Visual Environments and Standardized Precipitation Evapotranspiration Index (SPEI) during 1988–2018 over the continental US to investigate the association of spatial‐temporal variations of surface PM2.5 species with droughts. Ubiquitous decreasing trends in seasonal mean reconstructed PM2.5 are detected in all seasons except for the summer over the northwestern US. The increasing trend in the reconstructed PM2.5 in summer over northwestern US is primary due to the positive trend in total carbonaceous aerosols (TCAs), which more than offsets the negative trends in sulfate and nitrate aerosols. This also causes the contribution of TCA to the reconstructed PM2.5 to show an increasing trend in summer over the same region. The positive trend in TCA in summer over northwestern US is stronger under the drought than the wet conditions, hence resulting in a stronger positive trend in the contribution of TCA to the reconstructed PM2.5 in the drought conditions. Drought enhances TCA over northwestern US through its impact on wildfire, and the temporal change of TCA mainly follows the non‐linear variation of SPEI. Although droughts are found to have statistically significant impacts on the trends in sulfate, nitrate, and dust in other regions and seasons, the small contributions of these species to the reconstructed PM2.5 make their trend variations not sufficient to affect trends in the reconstructed PM2.5.
Dissecting exosome inhibitors: therapeutic insights into small-molecule chemicals against cancer
Authors: Kim Jong Hyun , Lee Chan-Hyeong , Baek Moon-Chang
Published: November 2022

Intensive research in the field of cancer biology has revealed unique methods of communication between cells through extracellular vesicles called exosomes. Exosomes are released from a broad spectrum of cell types and serve as functional mediators under physiological or pathological conditions. Hence, blocking the release of exosome bio carriers may prove useful for slowing the progression of certain types of cancers. Therefore, efforts are being made to develop exosome inhibitors to be used both as research tools and as therapies in clinical trials. Thus, studies on exosomes may lead to a breakthrough in cancer research, for which new clinical targets for different types of cancers are urgently needed. In this review, we briefly outline exosome inhibitors and discuss their modes of action and potential for use as therapeutic tools for cancer.
Neurovascular coupling in bone regeneration
Authors: Qin Qizhi , Lee Seungyong , Patel Nirali , Walden Kalah , Gomez-Salazar Mario , Levi Benjamin , James Aaron W.
Published: November 2022

The mammalian skeletal system is densely innervated by both neural and vascular networks. Peripheral nerves in the skeleton include sensory and sympathetic nerves. The crosstalk between skeletal and neural tissues is critical for skeletal development and regeneration. The cellular processes of osteogenesis and angiogenesis are coupled in both physiological and pathophysiological contexts. The cellular and molecular regulation of osteogenesis and angiogenesis have yet to be fully defined. This review will provide a detailed characterization of the regulatory role of nerves and blood vessels during bone regeneration. Furthermore, given the importance of the spatial relationship between nerves and blood vessels in bone, we discuss neurovascular coupling during physiological and pathological bone formation. A better understanding of the interactions between nerves and blood vessels will inform future novel therapeutic neural and vascular targeting for clinical bone repair and regeneration.
Discriminative binding of tau PET tracers PI2620, MK6240 and RO948 in Alzheimer’s disease, corticobasal degeneration and progressive supranuclear palsy brains
Authors: Malarte Mona-Lisa , Gillberg Per-Göran , Kumar Amit , Bogdanovic Nenad , Lemoine Laëtitia , Nordberg Agneta
Published: November 2022

Recent mechanistic and structural studies have challenged the classical tauopathy classification approach and revealed the complexity and heterogeneity of tau pathology in Alzheimer’s disease (AD) and primary tauopathies such as corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), progressing beyond distinct tau isoforms. In this multi-tau tracer study, we focused on the new second-generation tau PET tracers PI2620, MK6240 and RO948 to investigate this tau complexity in AD, CBD, and PSP brains using post-mortem radioligand binding studies and autoradiography of large and small frozen brain sections. Saturation binding studies indicated multiple binding sites for 3H-PI2620 in AD, CBD and PSP brains with different binding affinities (Kd ranging from 0.2 to 0.7 nM) and binding site densities (following the order: BmaxAD > BmaxCBD > BmaxPSP). Competitive binding studies complemented these findings, demonstrating the presence of two binding sites [super-high affinity (SHA): IC50(1) = 8.1 pM; and high affinity (HA): IC50(2) = 4.9 nM] in AD brains. Regional binding distribution studies showed that 3H-PI2620 could discriminate between AD (n = 6) and control cases (n = 9), especially in frontal cortex and temporal cortex tissue (p < 0.001) as well as in the hippocampal region (p = 0.02). 3H-PI2620, 3H-MK6240 and 3H-RO948 displayed similar binding behaviour in AD brains (in both homogenate competitive studies and one large frozen hemispherical brain section autoradiography studies) in terms of binding affinities, number of sites and regional patterns. Our small section autoradiography studies in the frontal cortex of CBD (n = 3) and PSP brains (n = 2) showed high specificity for 3H-PI2620 but not for 3H-MK6240 or 3H-RO948. Our findings clearly demonstrate different binding properties among the second-generation tau PET tracers, which may assist in further understanding of tau heterogeneity in AD versus non-AD tauopathies and suggests potential for development of pure selective 4R tau PET tracers.
Elevated FSP1 protects KRAS-mutated cells from ferroptosis during tumor initiation
Authors: Müller Fabienne , Lim Jonathan K. M. , Bebber Christina M. , Seidel Eric , Tishina Sofya , Dahlhaus Alina , Stroh Jenny , Beck Julia , Yapici Fatma Isil , Nakayama Keiko , Torres Fernández Lucia , Brägelmann Johannes , Leprivier Gabriel , von Karstedt Silvia
Published: November 2022

Oncogenic KRAS is the key driver oncogene for several of the most aggressive human cancers. One key feature of oncogenic KRAS expression is an early increase in cellular reactive oxygen species (ROS) which promotes cellular transformation if cells manage to escape cell death, mechanisms of which remain incompletely understood. Here, we identify that expression of oncogenic as compared to WT KRAS in isogenic cellular systems renders cells more resistant to ferroptosis, a recently described type of regulated necrosis. Mechanistically, we find that cells with mutant KRAS show a specific lack of ferroptosis-induced lipid peroxidation. Interestingly, KRAS-mutant cells upregulate expression of ferroptosis suppressor protein 1 (FSP1). Indeed, elevated levels of FSP1 in KRAS-mutant cells are responsible for mediating ferroptosis resistance and FSP1 is upregulated as a consequence of MAPK and NRF2 pathway activation downstream of KRAS. Strikingly, FSP1 activity promotes cellular transformation in soft agar and its overexpression is sufficient to promote spheroid growth in 3D in KRAS WT cells. Moreover, FSP1 expression and its activity in ferroptosis inhibition accelerates tumor onset of KRAS WT cells in the absence of oncogenic KRAS in vivo. Consequently, we find that pharmacological induction of ferroptosis in pancreatic organoids derived from the LsL-KRASG12D expressing mouse model is only effective in combination with FSP1 inhibition. Lastly, FSP1 is upregulated in non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) as compared to the respective normal tissue of origin and correlates with NRF2 expression in PDAC patient datasets. Based on these data, we propose that KRAS-mutant cells must navigate a ferroptosis checkpoint by upregulating FSP1 during tumor establishment. Consequently, ferroptosis-inducing therapy should be combined with FSP1 inhibitors for efficient therapy of KRAS-mutant cancers.
m6A-modified circFNDC3B inhibits colorectal cancer stemness and metastasis via RNF41-dependent ASB6 degradation
Authors: Zeng Wei , Zhu Jin-Feng , Guo Jian , Huang Gen-Jie , Ai Li-Sha , Zeng Yu , Liao Wang-Jun
Published: November 2022

Colorectal cancer (CRC) is the third most frequently diagnosed cancer with unfavorable clinical outcomes worldwide. circFNDC3B plays as a tumor suppressor in CRC, however, the mechanism of circFNDC3B in CRC remains ambiguous. The stem-like properties of CRC cells were detected by the evaluation of stemness markers, sphere formation assay and flow cytometry. qRT-PCR, FISH, IHC, and western blotting assessed the expression and localization of circFNDC3B, RNF41, ASB6, and stemness markers in CRC. The metastatic capabilities of CRC cells were examined by wound healing and Transwell assays, as well as in vivo liver metastasis model. Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assay and co-IP were used to detect the associations among circFNDC3B, FXR2, RNF41, and ASB6. Downregulated circFNDC3B was associated with unfavorite survival in CRC patients, and circFNDC3B overexpression suppressed CRC stemness and metastasis. Mechanistically, studies revealed that YTHDC1 facilitated cytoplasmic translocation of m6A-modified circFNDC3B, and circFNDC3B enhanced RNF41 mRNA stability and expression via binding to FXR2. circFNDC3B promoted ASB6 degradation through RNF41-mediated ubiquitination. Functional studies showed that silencing of RNF41 counteracted circFNDC3B-suppressed CRC stemness and metastasis, and ASB6 overexpression reversed circFNDC3B- or RNF41-mediated regulation of CRC stemness and metastasis. Elevated ASB6 was positively correlated with unfavorite survival in CRC patients. In vivo experiments further showed that circFNDC3B or RNF41 overexpression repressed tumor growth, stemness and liver metastasis via modulating ASB6. Taken together, m6A-modified circFNDC3B inhibited CRC stemness and metastasis via RNF41-dependent ASB6 degradation. These findings provide novel insights and important clues for targeted therapeutic strategies of CRC.
Identification of common and distinct origins of human serum and breastmilk IgA1 by mass spectrometry-based clonal profiling
Authors: Dingess Kelly A. , Hoek Max , van Rijswijk Danique M. H. , Tamara Sem , den Boer Maurits A. , Veth Tim , Damen Mirjam J. A. , Barendregt Arjan , Romijn Michelle , Juncker Hannah G. , van Keulen Britt J. , Vidarsson Gestur , van Goudoever Johannes B. , Bondt Albert , Heck Albert J. R.
Published: November 2022

The most abundant immunoglobulin present in the human body is IgA. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1-containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of their Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (∼80%) and dimeric joining (J-) chain coupled IgA1 (∼20%). Also, we confirmed that IgA1 in milk is present solely as secretory (S)IgA, consisting of two (∼50%), three (∼33%) or four (∼17%) IgA1 molecules assembled with a J-chain and secretory component (SC). Interestingly, the serum and milk IgA1-Fab repertoires were distinct between monomeric, and J-chain coupled dimeric IgA1. The serum dimeric J-chain coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter repertoire had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have (at least) two distinct origins; one of these produces dimeric J-chain coupled IgA1 molecules, shared in human serum and milk, and another produces monomeric IgA1 ending up exclusively in serum.
Evolutionary origins of the prolonged extant squamate radiation
Authors: Brownstein Chase D. , Meyer Dalton L. , Fabbri Matteo , Bhullar Bhart-Anjan S. , Gauthier Jacques A.
Published: November 2022

Squamata is the most diverse clade of terrestrial vertebrates. Although the origin of pan-squamates lies in the Triassic, the oldest undisputed members of extant clades known from nearly complete, uncrushed material come from the Cretaceous. Here, we describe three-dimensionally preserved partial skulls of two new crown lizards from the Late Jurassic of North America. Both species are placed at the base of the skink, girdled, and night lizard clade Pan-Scincoidea, which consistently occupies a position deep inside the squamate crown in both morphological and molecular phylogenies. The new lizards show that several features uniting pan-scincoids with another major lizard clade, the pan-lacertoids, in trees using morphology were convergently acquired as predicted by molecular analyses. Further, the palate of one new lizard bears a handful of ancestral saurian characteristics lost in nearly all extant squamates, revealing an underappreciated degree of complex morphological evolution in the early squamate crown. We find strong evidence for close relationships between the two new species and Cretaceous taxa from Eurasia. Together, these results suggest that early crown squamates had a wide geographic distribution and experienced complicated morphological evolution even while the Rhynchocephalia, now solely represented by the tuatara, was the dominant clade of lepidosaurs.
Rolling microswarms along acoustic virtual walls
Authors: Zhang Zhiyuan , Sukhov Alexander , Harting Jens , Malgaretti Paolo , Ahmed Daniel
Published: November 2022

Rolling is a ubiquitous transport mode utilized by living organisms and engineered systems. However, rolling at the microscale has been constrained by the requirement of a physical boundary to break the spatial homogeneity of surrounding mediums, which limits its prospects for navigation to locations with no boundaries. Here, in the absence of real boundaries, we show that microswarms can execute rolling along virtual walls in liquids, impelled by a combination of magnetic and acoustic fields. A rotational magnetic field causes individual particles to self-assemble and rotate, while the pressure nodes of an acoustic standing wave field serve as virtual walls. The acoustic radiation force pushes the microswarms towards a virtual wall and provides the reaction force needed to break their fore-aft motion symmetry and induce rolling along arbitrary trajectories. The concept of reconfigurable virtual walls overcomes the fundamental limitation of a physical boundary being required for universal rolling movements.
Genomic characteristics and comparative genomics analysis of Salmonella enterica subsp. enterica serovar Thompson isolated from an outbreak in South Korea
Authors: Lee Woojung , Kim Eiseul , Zin Hyunwoo , Sung Soohyun , Woo Jungha , Lee Min Jung , Yang Seung-Min , Kim Seung Hwan , Kim Soon Han , Kim Hae-Yeong
Published: November 2022

Salmonella infections represent an important public health problem. In 2018, a multistate outbreak of S. enterica subsp. enterica serovar Thompson infection associated with contaminated chocolate cakes in schools was reported in South Korea. In this study, we sequenced the 37 S. Thompson strains isolated from chocolate cakes, egg whites, preserves, and cookware associated with the outbreak. In addition, we analyze the genomic sequences of 61 S. Thompson strains (37 chocolate cake-related outbreak strains, 4 strains isolated from outbreaks in South Korea and 20 strains available in the National Center for Biotechnology Information) to assess the genomic characteristics of outbreak-related strains by comparative genomics and phylogenetic analysis. The results showed that identically classified clusters divided strains into two clusters, sub-clusters A & I (with strains from 2018 in South Korea) and sub-clusters B & II (with strains from 2014 to 2015 in South Korea). S. Thompson isolated from South Korea were accurately distinguished from publicly-available strains. Unlike other S. Thompson genomes, those of chocolate cake outbreak-related strains had three Salmonella phages (SEN8, vB SosS Oslo, and SI7) integrated into their chromosome. Comparative genomics revealed several genes responsible for the specific genomic features of chocolate cake outbreak-related strains and three bacteriophages that may contribute to the pathogenicity of other S. Thompson strains.
RNA-Seq exploration of the influence of stress on meat quality in Spanish goats
Authors: Naldurtiker Aditya , Batchu Phaneendra , Kouakou Brou , Terrill Thomas H. , Shaik Arshad , Kannan Govind
Published: November 2022

Studies exploring the transcriptome of stress and its effects on meat quality are very limited, particularly in goats. Fifty-four male Spanish goats (8-mo old; BW = 29.7 ± 2.03 kg) were randomly subjected to one of three treatments (TRT; n = 18 goats/treatment): (1) transported for 180 min, (2) transported for 30 min, or (3) held in pens (control) to analyze the transcriptome of stress and meat quality in goats using RNA-seq technology. Blood samples were collected before and after treatment, and meat samples were collected after humane slaughter for stress hormone, meat quality (Longissimus dorsi), and transcriptomic analysis. Plasma epinephrine concentrations were higher (P < 0.01) in 180 min and 30 min groups compared to the control group; however, norepinephrine concentrations were not affected by the treatment. Muscle glycogen concentrations (15 min postmortem) were lower (P < 0.01) in both 30 min and 180 min groups compared to the control group. Calpastatin levels were higher (P < 0.01) in 180 min and 30 min groups than the control group. Warner–Bratzler shear force values of loin chops were the highest in the 180 min group (4 ± 0.15, kg), lowest in the control group (3.51 ± 0.10, kg), and intermediate in the 30 min group (3.78 ± 0.09, kg;P < 0.01) both at day 1 and day 6 aging time. Additionally, desmin levels of day 6 samples were lowest in the control group, highest in 180 min group, and intermediate in 30 min group (P < 0.05). RNA-seq results showed that a total of 10,633 genes were differentially expressed (5194 up regulated; 5439 down regulated) among all comparisons (blood and day 1 and day 6 muscle samples). Among these differentially expressed genes (DEGs), KLF9, AMPK, FOXO3, PTX3, GADD45, PTPN1, CASP7, MAPK4, HSPA12A, and JAK-STAT were probably associated with the effects of stress on skeletal muscle proteins and involved in biological process such as cellular response to corticosteroid stimulus, endoplasmic reticulum stress, insulin resistance, DNA repair, apoptosis, MAPK cascade and regulation of proteolysis. The KEGG analysis revealed that AMPK and JAK-SAT signaling pathways and autophagy were among the top 20 enriched pathways in our treatment comparisons. The results provide an understanding of the genes and pathways involved in stress responses and related changes in postmortem muscle metabolism and meat quality characteristics in goats.
Localization versus delocalization of d-states within the $$\hbox {Ni}_{{2}}$$MnGa Heusler alloy
Authors: Janovec Jozef , Zelený Martin , Heczko Oleg , Ayuela Andrés
Published: November 2022

We present calculations based on density-functional theory with improved exchange-correlation approaches to investigate the electronic structure of $$\hbox {Ni}_2$$

Ni
2

MnGa magnetic shape memory alloy prototype. We study the effects of hybrid functionals as well as a Hubbard-like correction parameter U on the structural, electronic and magnetic properties of the alloy. We show that the previously successful application of U on Mn should be extended by including U on Ni to describe the d localized electrons more accurately and in better agreement with experiments. The bonding interactions within this intermetallic alloy are analysed including the role of non-transition metal. We found that the strongest and most stabilizing bond is formed between the Ga–Ni pairs due to the delocalized s–s and p–s orbital hybridization. Our findings suggest that minimization of the over-delocalization error introduced by standard semi-local exchange-correlation functionals leads to a better description of the $$\hbox {Ni}_2$$

Ni
2

MnGa alloy. Furthermore we propose that the experimental total magnetic moment of Ni–Mn–Ga alloys could be increased after carefully selected heat treatment procedures.
A real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events for niraparib
Authors: Guo Menglin , Shu Yamin , Chen Guosong , Li Juan , Li Feie
Published: November 2022

Niraparib was approved for the treatment of platinum-sensitive recurrent epithelial ovarian cancer, fallopian tube and primary peritoneal cancer. The authors retrospectively investigated niraparib-related adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Four algorithms were employed to quantify the signals of niraparib associated AEs, using data from the FAERS between 2017 and 2021. MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2019 and the GraphPad Prism 8 were used to conduct statistical analysis. There are 7,238,157 reports collected from the FAERS database, of which 11,701 reports listed niraparib as the ‘primary suspected (PS)’ drug. A total of 97 significant disproportionality PTs conforming to the four algorithms were simultaneously retained. Unexpected significant AEs such as neuropathy peripheral, photosensitivity reaction, gastrooesophageal reflux disease might also occur. The median onset time of niraparib-associated AEs was 18 days (interquartile range [IQR] 4–66 days), and most of the cases occurred within the first months after niraparib initiation. The study found niraparib-associated AEs and might provide important support for clinical monitoring and risk identification of niraparib.
mm-band surface acoustic wave devices utilizing two-dimensional boron nitride
Authors: Yoon Seok Hyun , Baek Chang-Ki , Kong Byoung Don
Published: November 2022

The simple structure, low power consumption, and small form factor have made surface acoustic wave (SAW) devices essential to mobile communication as RF filters. For instance, the latest 5G smartphones are equipped with almost 100 acoustic wave filters to select a specific frequency band and increase communication capacity. On the arrival of the newest communication standard, 5G, mm-band up to 39 GHz is supposed to be utilized, whereas the conventional SAW filters are limited to below 3 GHz, leaving a critical component missing. Here, we show an emerging 2D material—hexagonal boron nitride—can become a key enabler of mm-band SAW filter. Our study, based on first principles analysis and acousto-electric simulation, shows the operating frequency of SAW devices can reach over 20 GHz in its fundamental mode and 40 GHz in its interface mode with high electromechanical coupling coefficient (K2) and low insertion loss. In addition to the orders of magnitude improvement compared to the conventional SAW devices, our study provides a systematic approach to utilizing van der Waals crystals with highly anisotropic acoustic properties for practical applications.
In silico study on probing atomistic insights into structural stability and tensile properties of Fe-doped hydroxyapatite single crystals
Authors: Basu Subhadip , Nag Shubhadeep , Kottan Nihal B. , Basu Bikramjit
Published: November 2022

Hydroxyapatite (HA, Ca10PO4(OH)2) is a widely explored material in the experimental domain of biomaterials science, because of its resemblance with natural bone minerals. Specifically, in the bioceramic community, HA doped with multivalent cations (e.g., Mg2+, Fe2+, Sr2+, etc.) has been extensively investigated in the last few decades. Experimental research largely established the critical role of dopant content on mechanical and biocompatibility properties. The plethora of experimental measurements of mechanical response on doped HA is based on compression or indentation testing of polycrystalline materials. Such measurements, and more importantly the computational predictions of mechanical properties of single crystalline (doped) HA are scarce. On that premise, the present study aims to build atomistic models of Fe2+-doped HA with varying Fe content (10, 20, 30, and 40 mol%) and to explore their uniaxial tensile response, by means of molecular dynamics (MD) simulation. In the equilibrated unit cell structures, Ca(1) sites were found to be energetically favourable for Fe2+substitution. The local distribution of Fe2+ions significantly affects the atomic partial charge distribution and chemical symmetry surrounding the functional groups, and such signatures are found in the MD analyzed IR spectra. The significant decrease in the intensity of the IR bands found in the Fe-doped HA together with band splitting, because of the symmetry changes in the crystal structure. Another important objective of this work is to computationally predict the mechanical response of doped HA in their single crystal format. An interesting observation is that the elastic anisotropy of undoped HA was not compromised with Fe-doping. Tensile strength (TS) is systematically reduced in doped HA with Fe2+dopant content and a decrease in TS with temperature can be attributed to the increased thermal agitation of atoms at elevated temperatures. The physics of the tensile response was rationalized in terms of the strain dependent changes in covalent/ionic bond framework (Ca–P distance, P–O bond strain, O–P–O angular strain, O–H bond distance). Further, the dynamic changes in covalent bond network were energetically analyzed by calculating the changes in O–H and P–O bond vibrational energy. Summarizing, the current work establishes our foundational understanding of the atomistic phenomena involved in the structural stability and tensile response of Fe-doped HA single crystals.