bluuebunny/crossref_metadata_2025 huggingface dataset:
Diet containing dehulled adlay ameliorates hepatic steatosis, inflammation and insulin resistance in rats with non-alcoholic fatty liver disease
Authors: Yeh Wan-Ju , Ko Jung , Cheng Wei-Yi , Yang Hsin-Yi
Published: September 2021

Dietary modification plays a vital role in the treatment of non-alcoholic liver diseases. We investigated the effects of the consumption of a different amount of dehulled adlay, which has hypolipidaemic and anti-inflammatory properties, on non-alcoholic fatty liver disease (NAFLD). We fed rats a high-fat-high-fructose liquid diet for 16 weeks to induce NAFLD. The rats were divided into three groups fed the NAFLD diet only (NN) or a diet containing 44·9 or 89·8 g/l of dehulled adlay (NA and NB groups, respectively). After 8 weeks, the NA and NB groups had lower C-reactive protein levels and improvement in insulin resistance. In addition, the NB group had lower liver weight and hepatic TAG and cholesterol concentrations than did the NN group. Compared with the NN group, the high-dose NB group had improved steatosis, lower hepatic TNF-α, IL-1β and IL-6 levels and lower adipose leptin levels. Our results suggest that a diet containing dehulled adlay can ameliorate NAFLD progression by decreasing of insulin resistance, steatosis and inflammation.
Poor Lives Matter: COVID-19 and the Plight of Vulnerable Groups with Specific Reference to Poverty and Inequality in South Africa
Authors: Mubangizi John C
Published: September 2021

This article explores the impact of the COVID-19 pandemic on vulnerable people in South Africa in the specific context of poverty and inequality. It does so by first looking at the conceptual context and then highlighting the extent of the impact both from a constitutional and human rights context and from a legislative context. It uses the poor and vulnerable as a proxy to explore the impact of the pandemic (and the measures put in place to contain it) on the specific constitutional rights of vulnerable people, before suggesting a human rights-based approach to managing the pandemic. It concludes that, despite the South African government having undertaken some of the actions recommended, there remains room for improvement and scope for further research, as the pandemic is expected to continue for some time.
Truth and Truthfulness in Painting
Authors: Hyman John
Published: September 2021

This article explores the place of truth and truthfulness in painting and drawing, and criticises logocentrism in the theory of truth.
Normative ratings for 111 Swedish nouns and corresponding picture stimuli
Authors: Lehecka Tomas
Published: September 2021

Normative ratings are a means to control for the effects of confounding variables in psycholinguistic experiments. This paper introduces a new dataset of normative ratings for Swedish encompassing 111 concrete nouns and the corresponding picture stimuli in the MultiPic database (Duñabeitia et al. 2017). The norms for name agreement, category typicality, age of acquisition and subjective frequency were collected using online surveys among native speakers of the Finland-Swedish variety of Swedish. The paper discusses the inter-correlations between these variables and compares them against available ratings for other languages. In doing so, the paper argues that ratings for age of acquisition and subjective frequency collected for other languages may be applied to psycholinguistic studies on Finland-Swedish, at least with respect to concrete and highly imageable nouns. In contrast, norms for name agreement should be collected from speakers of the same language variety as represented by the subjects in the actual experiments.
Assessing Resilience in Older Adulthood: Development and Validation of the Resilience Scale for Older Adults
Authors: Wilson Claire A. , Plouffe Rachel A. , Saklofske Donald H.
Published: September 2021

This study presents on the initial development and validation of the Resilience Scale for Older Adults (RSOA). This new measure is based on a theoretical model of resilience grounded in qualitative research conducted with older adults. The scale consists of four resilience protective factors with 11 underlying facets. The Intrapersonal factor consists of Perseverance and Determination, Self-Efficacy and Independence, Purpose and Meaning, and Positive Perspective. The Interpersonal factor consists of Sense of Community, Family Support, and Friend/Neighbour Support. The Spiritual factor consists of Faith and Prayer, and the Experiential factor consists of Previous Adversity and Proactivity. The findings of three independent studies using older adult samples support the four-factor, 11-facet structure of the RSOA. Results also provide promising initial reliability and validity information, and analysis of gender invariance suggests that the factor structure is comparable across men and women. Implications for the applicability of the RSOA in research and clinical settings are discussed.
Child Sexual Abuse, Integrity Systems and the Anglican Church: Truth, Justice and Love
Authors: Miller Virginia , Miller Seumas
Published: September 2021

This article concerns child sexual abuse in the Anglican Church of Australia and the Church of England and, in particular, an integrity system to combat this problem and the ethical problems it gives rise to. The article relies on the findings of various commissions of inquiry to determine the nature and extent of child sexual abuse in the Anglican Church. The two salient ethical problems identified are: (1) design of safety measures in the light of the statistical preponderance of male on male sexuality; (2) justice issues arising from redress schemes established or proposed to provide redress to victims.
Reading the Church of England’s Response to the Covid-19 Crisis: The Diverging Views of Anglo-Catholic and Evangelical Clergy
Authors: Francis Leslie J. , Village Andrew
Published: September 2021

Within the one Church, the Church of England holds together in tension two distinctive streams, one rooted in the Catholic tradition (shaping Anglo-Catholic clergy) and one rooted in the Reformed tradition (shaping Evangelical clergy). Comparing the responses of 263 Anglo-Catholic clergy with the responses of 140 Evangelical clergy (all engaged in full-time stipendiary parish ministry) to the Coronavirus, Church & You Survey, the present analyses tested the thesis that these two groups would read the Church of England’s response to the Covid-19 crisis differently. The data demonstrated that, although Anglo-Catholic clergy were as willing as Evangelical clergy to embrace the digital age to assist with pastoral care, they were significantly less enthusiastic about the provision of online worship, about the closure of churches, and about the notion of virtual rather than geographical communities. The centrality of sacred space (parish church) and local place (parish system) remain more important in the Catholic tradition than in the Reformed tradition. As a consequence, Anglo-Catholic clergy have felt more disadvantaged and marginalized by the Church of England’s response to the Covid-19 crisis.
Introduction to the special issue on institutions and culture in economic contexts
Authors: Andriani Luca , Luca Bruno Randolph
Published: September 2021

The need of further research on the interlink between culture and institutions has been strongly advocated by economists and institutionalists alike. However, bringing together culture and institutions within an organic framework, though, is a non-trivial operation. This is due to the complexity of the synergies between cultural aspects and institutional devices. This special issue attempts to start filling this gap and to build anad-hocsystemic platform for disseminating such a debate. To this purpose, it brings together an organic collection of contributions in well-established conceptualisations of both culture and institutions, supported by robust and consistent methodological applications. The essays presented in this work provide consistent evidence and conceptual perspectives supporting the idea that the synergies between cultural and institutional aspects are of paramount importance to understand human behaviour, individuals' choices and societies' patterns. They also improve the theoretical, empirical and methodological understanding of the role of institutions and culture in different geopolitical and socio-economic realms. By doing so, these contributions place this special issue as prelude to further research on the co-evolution of culture and institutions and on its possible implications on different societal aspects, human development and well-being.
Clinical supervision in CBT training: what do participants view as effective?
Authors: Kelly Nicola , Hassett Alex
Published: September 2021

Literature pertaining to cognitive behavioural therapy (CBT) supervision is limited, particularly about CBT supervision during training. This exploratory study outlines the thoughts of supervisors and supervisees in a training context about which elements make supervision effective. Four supervisees and four experienced CBT supervisors (all from a CBT training programme and independent of one another) were interviewed and asked to consider what makes CBT supervision during training effective. Their responses were evaluated using thematic analysis (TA) and key themes identified. The fit with existing literature was considered via the use of an adapted Delphi poll. Two main themes, containing seven subthemes, were identified from the thematic analysis: ‘supervision as structured learning’ and ‘supervisory relations and process’. The adapted Delphi poll was divided into six categories denoting important characteristics of CBT supervision: (1) the supervisory relationship, (2) ethical factors, (3) generic supervisory skills, (4) mirroring the CBT approach, (5) the supervisor’s knowledge and (6) addressing difficulties. There was a good fit between the TA themes and the Delphi categories. For those engaging in CBT supervision, establishing a structure that mirrors a CBT session, alongside a supportive supervisory alliance, may promote effective CBT supervision during training.

Key learning aims

(1)

To consider what might make CBT supervision during training a better experience for participants, such as alliance factors and structured learning.

(2)

To discover how supervisors’ and trainees’ perspectives fit with existing research on CBT supervision.

(3)

To consider some potential supervisory implications related to aspects of CBT supervision that participants find useful.
Interprofessional Suicide Prevention Education
Authors: La Guardia Amanda C. , Wright-Berryman Jennifer , Cramer Robert J. , Kaniuka Andrea R. , Tufts Kimberly Adams
Published: September 2021

Abstract. The COVID-19 pandemic has raised concerns regarding possible spikes in suicidal behavior in light of heightened risk factors such as social isolation and financial strain; thus, comprehensive suicide prevention training for emerging health service providers is increasingly vital. This article summarizes an interprofessional education (IPE) suicide prevention course delivered in-person in Spring 2020. Pilot data demonstrate that despite the impact of COVID-19 on higher education, this course had long-term impacts on trainee suicide prevention efficacy, IPE attitudes, and use of course content in practice. Discussion serves to address enhancements for interprofessional and suicide prevention education during and after the pandemic. Emphasis is placed on adaptable training strategies, considerations in the delivery format, guidelines for intensive virtual meetings with trainee teams, and future directions in IPE suicide prevention training research.
Geochemical and C‐O Isotopic Study of Ophiolite‐Derived Carbonates of the Barzaman Formation, Oman: Evidence of Natural CO2 Sequestration Via Carbonation of Ultramafic Clasts
Authors: Ali Arshad , Abbasi Iftikhar Ahmed , Nogueira Leonardo Brandão , Hersi Osman Salad , Al Kindi Sumaiya A. N. , El‐Ghali Mohamed A. K. , Nasir Sobhi Jaber
Published: September 2021

Carbonate precipitation through atmospheric CO2 uptake by alkaline‐hyperalkaline waters offers a potential approach to mitigating anthropogenic CO2 emissions. The Oman Ophiolite produces high‐pH water characterized by continuous sequestration of CO2 at the air‐water interface. The geochemical and isotopic data of carbonates from the Barzaman Formation is used to assess the amount of atmospheric CO2 stored in the dolomite‐calcite assemblage. Post Archean Australian Shale ‐normalized rare earth elements patterns, with the exception of La and Ce anomalies, are similar to those of the bulk oceanic and lower crusts, with increasing LREE and flat HREE trends, and a positive Eu anomaly. The δ13CVPDB and δ18OVSMOW isotope values of the analyzed samples show two distinct end‐members, in which dolomite (−7.77‰ and +27.3‰) is isotopically heavier than calcite (−9.93‰ and +21.5‰). The estimated carbonate growth temperatures (18°C–56°C) are indistinguishable from the previously reported range (18°C–66°C). The C‐O isotope model for calcite, groundwater, and atmospheric CO2 shows that an ophiolite‐derived calcite sample absorbed an unequivocal amount of atmospheric CO2 (78% ± 11%) during precipitation. At the same time, dissolved inorganic carbon (DIC) in water accounts for the remaining carbon contribution (22% ± 9%). DIC is closely associated with different carbonate lithofacies and ophiolite‐derived soil, exhibiting large variations in C‐O isotopic compositions caused by isotopic disequilibrium. Taken together, geochemical and isotopic properties confirm that the carbonates were formed under oxic conditions triggered by the water‐rock interaction. For a reliable estimate of CO2 sequestered by carbonates of the Barzaman Formation, a systematic groundwater analysis is recommended to determine the contribution of CO2 in DIC.
Synchronous Emplacement of the Anorthosite Xenolith‐Bearing Beaver River Diabase and One of the Largest Lava Flows on Earth
Authors: Zhang Yiming , Swanson‐Hysell Nicholas L. , Schmitz Mark D. , Miller James D. , Avery Margaret S.
Published: September 2021

New geochronologic and paleomagnetic data from the North American Midcontinent Rift (MCR) reveal the synchronous emplacement of the Beaver River diabase, the anorthosite xenoliths within it, and the Greenstone Flow—one of the largest lava flows on Earth. A U‐Pb zircon date of 1091.83  0.21 Ma (2) from one of the anorthosite xenoliths is consistent with the anorthosite cumulate forming as part of the MCR and provides a maximum age constraint for the Beaver River diabase. Paired with the minimum age constraint of a cross‐cutting Silver Bay intrusion (1091.61  0.14 Ma; 2), these data tightly bracket the age of the Beaver River diabase to be 1091.7  0.2 Ma (95% CI), coeval with the eruption of the Greenstone Flow (1091.59  0.27 Ma; 2)—which is further supported by indistinguishable tilt‐corrected paleomagnetic pole positions. Geochronological, paleomagnetic, mineralogical and geochemical data are consistent with a hypothesis that the Beaver River diabase was the feeder system for the Greenstone Flow. The large areal extent of the intrusives and large estimated volume of the volcanics suggest that they represent a rapid and voluminous ca. 1,092 Ma magmatic pulse near the end of the main stage of MCR magmatism.
Stratospheric Fluorine as a Tracer of Circulation Changes: Comparison Between Infrared Remote‐Sensing Observations and Simulations With Five Modern Reanalyses
Authors: Prignon M. , Chabrillat S. , Friedrich M. , Smale D. , Strahan S. E. , Bernath P. F. , Chipperfield M. P. , Dhomse S. S. , Feng W. , Minganti D. , Servais C. , Mahieu E.
Published: September 2021

Using multidecadal time series of ground‐based and satellite Fourier transform infrared measurements of inorganic fluorine (i.e., total fluorine resident in stratospheric fluorine reservoirs), we investigate stratospheric circulation changes over the past 20 years. The representation of these changes in five modern reanalyses is further analyzed through chemical‐transport model (CTM) simulations. From the observations but also from all reanalyses, we show that the inorganic fluorine is accumulating less rapidly in the Southern Hemisphere than in the Northern Hemisphere during the 21st century. Comparisons with a study evaluating the age‐of‐air of these reanalyses using the same CTM allow us to link this hemispheric asymmetry to changes in the Brewer‐Dobson circulation (BDC), with the age‐of‐air of the Southern Hemisphere getting younger relative to that of the Northern Hemisphere. Large differences in simulated total columns and absolute trend values are, nevertheless, depicted between our simulations driven by the five reanalyses. Superimposed on this multidecadal change, we, furthermore, confirm a 5–7‐year variability of the BDC that was first described in a recent study analyzing long‐term time series of hydrogen chloride (HCl) and nitric acid (HNO3). It is important to stress that our results, based on observations and meteorological reanalyses, are in contrast with the projections of chemistry‐climate models in response to the coupled increase of greenhouse gases and decrease of ozone‐depleting substances, calling for further investigations and the continuation of long‐term observations.
An Eddy‐Resolving Numerical Model to Study Turbulent Flow, Sediment, and Bed Evolution Using Detached Eddy Simulation in a Lateral Separation Zone at the Field‐Scale
Authors: Alvarez Laura V. , Grams Paul E.
Published: September 2021

Turbulence‐resolving simulations elucidate key elements of fluid dynamics and sediment transport in fluvial environments. This research presents a feasible strategy for applying state‐of‐the‐art computational fluid mechanics to the study of sediment transport and morphodynamic processes in lateral separation zones, which are common features in canyon rivers where massive lateral flow separation causes large‐scale turbulence that controls sediment erosion and deposition. An eddy‐resolving model was developed and tested at the field‐scale, coupling a viscous flow and sediment transport solver using Detached Eddy Simulation techniques. A morphodynamic model was applied to the viscous flow/sediment solver to calculate erosion and deposition. A simulation of turbulence was performed at the grid resolution for a straight channel to determine the relative contributions of modeled and resolved diffusivity. The time‐dependent, energetically important, correlative, non‐stationary signals of the simulated quantities were captured at the lateral separation zone. Strong periodic signals featured by high amplitude were found at the separation zone, while low frequency pulsations were observed at the reattachment zone of the lateral separation zone. Interactions between the eddies and the loose bed boundaries resulted in erosion of sediment at the main channel followed by deposition at the primary eddy and eddy bars.
Are Deep Aquifers Really Confined? Insights From Deep Groundwater Tidal Responses in the North China Platform
Authors: Zhang Yan , Wang Chi‐Yuen , Fu Li‐Yun , Yang Qiu‐Ye
Published: September 2021

Many deep aquifers overlain by barrier formations in the continental US are used as geological repositories for wastewaters coproduced from hydrocarbon exploration. This practice is to protect shallow groundwater following the US Environmental Protection Agency’s regulation. Implicit in such practice is the assumption that deep aquifers overlain by mudstones or shales are confined so that the injected fluids will not migrate upward to contaminate shallow groundwater. However, no systematic test of this hypothesis has been made. Here we invert the groundwater response to both the M2 and the O1 tides and to the barometric pressure across a large (2.046 × 106 km2) geologic regime, the North China Platform, to systematically evaluate the hydraulic parameters as functions of depth and time without a priori assumption. Our result, the first of such inversion, shows no depth dependence of aquifer confinement to a depth of 3,400 m and that deep confined aquifers overlain by barrier formations may become leaky after distant earthquakes. It suggests that monitoring of aquifer confinement may be needed to ensure if the targeted deep aquifer for wastewater injection is really confined. The results may be timely and of global significance because the practice of hydrofracking for natural gas and the deep injection for the disposal of the coproduced wastewaters in the US may soon be adopted by other countries, such as China.
Laboratory Flume and Numerical Modeling Experiments Show Log Jams and Branching Channels Increase Hyporheic Exchange
Authors: Wilhelmsen K. , Sawyer A. H. , Marshall A. , McFadden S. , Singha K. , Wohl E.
Published: September 2021

Log jams alter gradients in hydraulic head, increase the area available for hyporheic exchange by creating backwater areas, and lead to the formation of multiple channel branches and bars that drive additional exchange. Here, we numerically simulated stream‐groundwater interactions for two constructed flume systems—one without jams and one with a series of three jams—to quantify the effects of interacting jam structures and channel branches on hyporheic exchange at three stream flow rates. In simulations without jams, average hyporheic exchange rates ranged from 2.1 × 10−4 to 2.9 × 10−4 m/s for various stream discharge scenarios, but with jams, exchange rates increased to a range of 1.3 × 10−3–3.5 × 10−3 m/s. Largely due to these increased hyporheic exchange rates, jams increased stream‐groundwater connectivity or decreased the turnover length that stream water travels before interacting with the hyporheic zone, by an order of magnitude, and drove long flow paths that connected multiple jams and channel threads. Decreased turnover lengths corresponded with greater reaction significance per km, a measure of the potential for the hyporheic zone to influence stream water chemistry. For low‐flow conditions, log jams increased reaction significance per km five‐fold, from 0.07 to 0.35. Jams with larger volumes led to longer hyporheic residence times and path lengths that exhibited multiple scales of exchange. Additionally, the longest flow paths connecting multiple jams occurred in the reach with multiple channel branches. These findings suggest that large gains in hydrologic connectivity can be achieved by promoting in‐stream wood accumulation and the natural formation of both jams and branching channels.
Genomic and transcriptomic analyses reveal a tandem amplification unit of 11 genes and mutations in mismatch repair genes in methotrexate-resistant HT-29 cells
Authors: Kim Ahreum , Shin Jong-Yeon , Seo Jeong-Sun
Published: September 2021

DHFR gene amplification is commonly present in methotrexate (MTX)-resistant colon cancer cells and acute lymphoblastic leukemia. In this study, we proposed an integrative framework to characterize the amplified region by using a combination of single-molecule real-time sequencing, next-generation optical mapping, and chromosome conformation capture (Hi-C). We identified an amplification unit spanning 11 genes, from the DHFR gene to the ATP6AP1L gene position, with high adjusted interaction frequencies on chromosome 5 (~2.2 Mbp) and a twenty-fold tandemly amplified region, and novel inversions at the start and end positions of the amplified region as well as frameshift insertions in most of the MSH and MLH genes were detected. These mutations might stimulate chromosomal breakage and cause the dysregulation of mismatch repair. Characterizing the tandem gene-amplified unit may be critical for identifying the mechanisms that trigger genomic rearrangements. These findings may provide new insight into the mechanisms underlying the amplification process and the evolution of drug resistance.
Inter-rater reliability of the neonatal adverse event severity scale using real-world Neonatal clinical trial data
Authors: Lewis Tamorah , Terrin Norma , Davis Jonathan , Michels Kurt , Salaets Thomas , Wade Kelly ,   International Neonatal Consortium
Published: September 2021

Objective

The Neonatal Adverse Event Severity Scale (NAESS) was developed to improve scoring of neonatal adverse events (AEs) and accelerate neonatal drug development. This is the first validation study of the novel tool.

Study design

Retrospective validation study assessing the inter-rater reliability (IRR) of the NAESS. Reviewers used real-world AE data from a neonatal trial. Intra-class correlation (ICC) statistical analysis was performed.

Result

Sixty AEs were randomly assigned to twelve reviewers for a total of 240 severity scores. Generic and AE-specific NAESS tables were assessed. The ICC was 0.63 (95% confidence interval 0.51 to 0.73). Percent variation due to reviewer and residual error was 0.03 and 0.34, respectively.

Conclusion

In this first study of the NAESS tool, an ICC of 0.63 indicates moderate reliability. Results highlight the need for improved data collection on neonatal AE forms, augmented training on the NAESS tool, and will inform the prospective validation studies.
AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1–Bcl-6 axis-mediated B-cell differentiation
Authors: Yang Ming , Long Di , Hu Longyuan , Zhao Zhidan , Li Qianwen , Guo Yunkai , He Zhenghao , Zhao Ming , Lu Liwei , Li Fen , Long Hai , Wu Haijing , Lu Qianjin
Published: September 2021

Absent in melanoma 2 (AIM2) has been reported to be a component of inflammasomes in innate immune cells. Surprisingly, AIM2 is expressed by B cells, and higher AIM2 expression is observed in the B cells from lupus patients. To date, the inflammasome-independent function of AIM2 in B cells remains unclear. Here, we report increased expression of AIM2 in human tonsil memory and germinal center (GC) B cells and in memory B cells and plasma cells from the circulation and skin lesions of lupus patients. Conditional knockout of AIM2 in B cells reduces the CD19+ B-cell frequency in lymph nodes and spleens, and dampens KLH-induced IgG1-antibody production. In a pristane-induced mouse model of lupus, AIM2 deficiency in B cells attenuates lupus symptoms and reduces the frequency of GC B cells, T follicular helper (Tfh) cells, plasmablast cells, and plasma cells. Furthermore, the loss of AIM2 in human B cells leads to the increased expression of Blimp-1 and reduces the expression of Bcl-6. However, the silencing of Blimp-1 and Bcl-6 has no significant effect on AIM2 expression, indicating that AIM2 might be the upstream regulator for Blimp-1 and Bcl-6. In addition, IL-10 is found to upregulate AIM2 expression via DNA demethylation. Together, our findings reveal that AIM2 is highly expressed in the B cells of lupus patients and promotes B-cell differentiation by modulating the Bcl-6–Blimp-1 axis, providing a novel target for SLE treatment.
Plant-microbe interactions in the phyllosphere: facing challenges of the anthropocene
Authors: Perreault Rosaëlle , Laforest-Lapointe Isabelle
Published: September 2021

Global change is a defining feature of the Anthropocene, the current human-dominated epoch, and poses imminent threats to ecosystem dynamics and services such as plant productivity, biodiversity, and environmental regulation. In this era, terrestrial ecosystems are experiencing perturbations linked to direct habitat modifications as well as indirect effects of global change on species distribution and extreme abiotic conditions. Microorganisms represent an important reservoir of biodiversity that can influence macro-organisms as they face habitat loss, rising atmospheric CO2 concentration, pollution, global warming, and increased frequency of drought. Plant-microbe interactions in the phyllosphere have been shown to support plant growth and increase host resistance to biotic and abiotic stresses. Here, we review how plant-microbe interactions in the phyllosphere can influence host survival and fitness in the context of global change. We highlight evidence that plant-microbe interactions (1) improve urban pollution remediation through the degradation of pollutants such as ultrafine particulate matter, black carbon, and atmospheric hydrocarbons, (2) have contrasting impacts on plant species range shifts through the loss of symbionts or pathogens, and (3) drive plant host adaptation to drought and warming. Finally, we discuss how key community ecology processes could drive plant-microbe interactions facing challenges of the Anthropocene.
In vitro and in vivo activity of GT-1, a novel siderophore cephalosporin, and GT-055, a broad-spectrum β-lactamase inhibitor, against biothreat and ESKAPE pathogens
Authors: Halasohoris Stephanie A. , Scarff Jennifer M. , Pysz Lisa M. , Lembirik Sanae , Lemmon Margaret M. , Biek Donald , Hannah Brendan , Zumbrun Steven D. , Panchal Rekha G.
Published: September 2021

Antimicrobial-resistance (AMR) has become an increasingly difficult issue to overcome for bacteria associated with both community- and hospital-acquired infections as well as potential biodefense threats. The need to identify new therapeutics of novel classes and/or with unique mechanisms is critical to combatting AMR in the coming years. GT-1 (LCB10-0200), a siderophore-linked cephalosporin, is one such novel option and is formulated to be used either alone or in combination with a novel broad-spectrum β-lactamase inhibitor, GT-055 (LCB18-055). This study assessed the in vitro and in vivo efficacy of GT-1 and GT-055 against a broad array of multi-drug resistant and biothreat pathogens. Here, we demonstrated sub-4 µg ml−1 efficacy against a number of pathogens in vitro. We further determined that in mice infected via aerosol route with Yersinia pestis, efficacy of GT-1/GT-055 treatment is at least equivalent to the comparator antibiotic, ciprofloxacin.
Tunable and functional deep eutectic solvents for lignocellulose valorization
Authors: Liu Yongzhuang , Deak Noemi , Wang Zhiwen , Yu Haipeng , Hameleers Lisanne , Jurak Edita , Deuss Peter J. , Barta Katalin
Published: September 2021

Stabilization of reactive intermediates is an enabling concept in biomass fractionation and depolymerization. Deep eutectic solvents (DES) are intriguing green reaction media for biomass processing; however undesired lignin condensation is a typical drawback for most acid-based DES fractionation processes. Here we describe ternary DES systems composed of choline chloride and oxalic acid, additionally incorporating ethylene glycol (or other diols) that provide the desired ‘stabilization’ function for efficient lignocellulose fractionation, preserving the quality of all lignocellulose constituents. The obtained ethylene-glycol protected lignin displays high β-O-4 content (up to 53 per 100 aromatic units) and can be readily depolymerized to distinct monophenolic products. The cellulose residues, free from condensed lignin particles, deliver up to 95.9 ± 2.12% glucose yield upon enzymatic digestion. The DES can be recovered with high yield and purity and re-used with good efficiency. Notably, we have shown that the reactivity of the β-O-4 linkage in model compounds can be steered towards either cleavage or stabilization, depending on DES composition, demonstrating the advantage of the modular DES composition.
New-onset IgG autoantibodies in hospitalized patients with COVID-19
Authors: Chang Sarah Esther , Feng Allan , Meng Wenzhao , Apostolidis Sokratis A. , Mack Elisabeth , Artandi Maja , Barman Linda , Bennett Kate , Chakraborty Saborni , Chang Iris , Cheung Peggie , Chinthrajah Sharon , Dhingra Shaurya , Do Evan , Finck Amanda , Gaano Andrew , Geßner Reinhard , Giannini Heather M. , Gonzalez Joyce , Greib Sarah , Gündisch Margrit , Hsu Alex Ren , Kuo Alex , Manohar Monali , Mao Rong , Neeli Indira , Neubauer Andreas , Oniyide Oluwatosin , Powell Abigail E. , Puri Rajan , Renz Harald , Schapiro Jeffrey , Weidenbacher Payton A. , Wittman Richard , Ahuja Neera , Chung Ho-Ryun , Jagannathan Prasanna , James Judith A. , Kim Peter S. , Meyer Nuala J. , Nadeau Kari C. , Radic Marko , Robinson William H. , Singh Upinder , Wang Taia T. , Wherry E. John , Skevaki Chrysanthi , Luning Prak Eline T. , Utz Paul J.
Published: September 2021

COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.
Phylogenetic conservatism drives nutrient dynamics of coral reef fishes
Authors: Allgeier Jacob E. , Weeks Brian C. , Munsterman Katrina S. , Wale Nina , Wenger Seth J. , Parravicini Valeriano , Schiettekatte Nina M. D. , Villéger Sébastien , Burkepile Deron E.
Published: September 2021

The relative importance of evolutionary history and ecology for traits that drive ecosystem processes is poorly understood. Consumers are essential drivers of nutrient cycling on coral reefs, and thus ecosystem productivity. We use nine consumer “chemical traits” associated with nutrient cycling, collected from 1,572 individual coral reef fishes (178 species spanning 41 families) in two biogeographic regions, the Caribbean and Polynesia, to quantify the relative importance of phylogenetic history and ecological context as drivers of chemical trait variation on coral reefs. We find: (1) phylogenetic relatedness is the best predictor of all chemical traits, substantially outweighing the importance of ecological factors thought to be key drivers of these traits, (2) phylogenetic conservatism in chemical traits is greater in the Caribbean than Polynesia, where our data suggests that ecological forces have a greater influence on chemical trait variation, and (3) differences in chemical traits between regions can be explained by differences in nutrient limitation associated with the geologic context of our study locations. Our study provides multiple lines of evidence that phylogeny is a critical determinant of contemporary nutrient dynamics on coral reefs. More broadly our findings highlight the utility of evolutionary history to improve prediction in ecosystem ecology.
Designing efficient genetic code expansion in Bacillus subtilis to gain biological insights
Authors: Stork Devon A. , Squyres Georgia R. , Kuru Erkin , Gromek Katarzyna A. , Rittichier Jonathan , Jog Aditya , Burton Briana M. , Church George M. , Garner Ethan C. , Kunjapur Aditya M.
Published: September 2021

Bacillus subtilis is a model gram-positive bacterium, commonly used to explore questions across bacterial cell biology and for industrial uses. To enable greater understanding and control of proteins in B. subtilis, here we report broad and efficient genetic code expansion in B. subtilis by incorporating 20 distinct non-standard amino acids within proteins using 3 different families of genetic code expansion systems and two choices of codons. We use these systems to achieve click-labelling, photo-crosslinking, and translational titration. These tools allow us to demonstrate differences between E. coli and B. subtilis stop codon suppression, validate a predicted protein-protein binding interface, and begin to interrogate properties underlying bacterial cytokinesis by precisely modulating cell division dynamics in vivo. We expect that the establishment of this simple and easily accessible chemical biology system in B. subtilis will help uncover an abundance of biological insights and aid genetic code expansion in other organisms.
Non-fullerene acceptor organic photovoltaics with intrinsic operational lifetimes over 30 years
Authors: Li Yongxi , Huang Xiaheng , Ding Kan , Sheriff Hafiz K. M. , Ye Long , Liu Haoran , Li Chang-Zhi , Ade Harald , Forrest Stephen R.
Published: September 2021

Organic photovoltaic cells (OPVs) have the potential of becoming a productive renewable energy technology if the requirements of low cost, high efficiency and prolonged lifetime are simultaneously fulfilled. So far, the remaining unfulfilled promise of this technology is its inadequate operational lifetime. Here, we demonstrate that the instability of NFA solar cells arises primarily from chemical changes at organic/inorganic interfaces bounding the bulk heterojunction active region. Encapsulated devices stabilized by additional protective buffer layers as well as the integration of a simple solution processed ultraviolet filtering layer, maintain 94% of their initial efficiency under simulated, 1 sun intensity, AM1.5 G irradiation for 1900 hours at 55 °C. Accelerated aging is also induced by exposure of light illumination intensities up to 27 suns, and operation temperatures as high as 65 °C. An extrapolated intrinsic lifetime of > 5.6 × 104 h is obtained, which is equivalent to 30 years outdoor exposure.
Pressure induced superconductivity in MnSe
Authors: Hung T. L. , Huang C. H. , Deng L. Z. , Ou M. N. , Chen Y. Y. , Wu M. K. , Huyan S. Y. , Chu C. W. , Chen P. J. , Lee T. K.
Published: September 2021

The rich phenomena in the FeSe and related compounds have attracted great interests as it provides fertile material to gain further insight into the mechanism of high temperature superconductivity. A natural follow-up work was to look into the possibility of superconductivity in MnSe. We demonstrated in this work that high pressure can effectively suppress the complex magnetic characters of MnSe, and induce superconductivity with Tc ~ 5 K at pressure ~12 GPa confirmed by both magnetic and resistive measurements. The highest Tc is ~ 9 K (magnetic result) at ~35 GPa. Our observations suggest the observed superconductivity may closely relate to the pressure-induced structural change. However, the interface between the metallic and insulating boundaries may also play an important role to the pressure induced superconductivity in MnSe.
Intrinsically disordered protein biosensor tracks the physical-chemical effects of osmotic stress on cells
Authors: Cuevas-Velazquez Cesar L. , Vellosillo Tamara , Guadalupe Karina , Schmidt Hermann Broder , Yu Feng , Moses David , Brophy Jennifer A. N. , Cosio-Acosta Dante , Das Alakananda , Wang Lingxin , Jones Alexander M. , Covarrubias Alejandra A. , Sukenik Shahar , Dinneny José R.
Published: September 2021

Cell homeostasis is perturbed when dramatic shifts in the external environment cause the physical-chemical properties inside the cell to change. Experimental approaches for dynamically monitoring these intracellular effects are currently lacking. Here, we leverage the environmental sensitivity and structural plasticity of intrinsically disordered protein regions (IDRs) to develop a FRET biosensor capable of monitoring rapid intracellular changes caused by osmotic stress. The biosensor, named SED1, utilizes the Arabidopsis intrinsically disordered AtLEA4-5 protein expressed in plants under water deficit. Computational modeling and in vitro studies reveal that SED1 is highly sensitive to macromolecular crowding. SED1 exhibits large and near-linear osmolarity-dependent changes in FRET inside living bacteria, yeast, plant, and human cells, demonstrating the broad utility of this tool for studying water-associated stress. This study demonstrates the remarkable ability of IDRs to sense the cellular environment across the tree of life and provides a blueprint for their use as environmentally-responsive molecular tools.
One-step construction of circularized nanodiscs using SpyCatcher-SpyTag
Authors: Zhang Shanwen , Ren Qian , Novick Scott J. , Strutzenberg Timothy S. , Griffin Patrick R. , Bao Huan
Published: September 2021

Circularized nandiscs (cNDs) exhibit superb monodispersity and have the potential to transform functional and structural studies of membrane proteins. In particular, cNDs can stabilize large patches of lipid bilayers for the reconstitution of complex membrane biochemical reactions, enabling the capture of crucial intermediates involved in synaptic transmission and viral entry. However, previous methods for building cNDs require multiple steps and suffer from low yields. We herein introduce a simple, one-step approach to ease the construction of cNDs using the SpyCatcher-SpyTag technology. This approach increases the yield of cNDs by over 10-fold and is able to rapidly generates cNDs with diameters ranging from 11 to over 100 nm. We demonstrate the utility of these cNDs for mechanistic interrogations of vesicle fusion and protein-lipid interactions that are unattainable using small nanodiscs. Together, the remarkable performance of SpyCatcher-SpyTag in nanodisc circularization paves the way for the use of cNDs in membrane biochemistry and structural biology.
Allosteric modulation of LRRC8 channels by targeting their cytoplasmic domains
Authors: Deneka Dawid , Rutz Sonja , Hutter Cedric A. J. , Seeger Markus A. , Sawicka Marta , Dutzler Raimund
Published: September 2021

Members of the LRRC8 family form heteromeric assemblies, which function as volume-regulated anion channels. These modular proteins consist of a transmembrane pore and cytoplasmic leucine-rich repeat (LRR) domains. Despite their known molecular architecture, the mechanism of activation and the role of the LRR domains in this process has remained elusive. Here we address this question by generating synthetic nanobodies, termed sybodies, which target the LRR domain of the obligatory subunit LRRC8A. We use these binders to investigate their interaction with homomeric LRRC8A channels by cryo-electron microscopy and the consequent effect on channel activation by electrophysiology. The five identified sybodies either inhibit or enhance activity by binding to distinct epitopes of the LRR domain, thereby altering channel conformations. In combination, our work provides a set of specific modulators of LRRC8 proteins and reveals the role of their cytoplasmic domains as regulators of channel activity by allosteric mechanisms.
Single-cell RNA sequencing of peripheral blood mononuclear cells from acute Kawasaki disease patients
Authors: Wang Zhen , Xie Lijian , Ding Guohui , Song Sirui , Chen Liqin , Li Guang , Xia Min , Han Dingding , Zheng Yue , Liu Jia , Xiao Tingting , Zhang Hong , Huang Yujuan , Li Yixue , Huang Min
Published: September 2021

Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although functional and phenotypic changes of immune cells have been reported, a global understanding of immune responses underlying acute KD is unclear. Here, using single-cell RNA sequencing, we profile peripheral blood mononuclear cells from seven patients with acute KD before and after intravenous immunoglobulin therapy and from three age-matched healthy controls. The most differentially expressed genes are identified in monocytes, with high expression of pro-inflammatory mediators, immunoglobulin receptors and low expression of MHC class II genes in acute KD. Single-cell RNA sequencing and flow cytometry analyses, of cells from an additional 16 KD patients, show that although the percentage of total B cells is substantially decreased after therapy, the percentage of plasma cells among the B cells is significantly increased. The percentage of CD8+T cells is decreased in acute KD, notably effector memory CD8+T cells compared with healthy controls. Oligoclonal expansions of both B cell receptors and T cell receptors are observed after therapy. We identify biological processes potentially underlying the changes of each cell type. The single-cell landscape of both innate and adaptive immune responses provides insights into pathogenesis and therapy of KD.
Mechanosensitive recruitment of stator units promotes binding of the response regulator CheY-P to the flagellar motor
Authors: Antani Jyot D. , Gupta Rachit , Lee Annie H. , Rhee Kathy Y. , Manson Michael D. , Lele Pushkar P.
Published: September 2021

Reversible switching of the bacterial flagellar motor between clockwise (CW) and counterclockwise (CCW) rotation is necessary for chemotaxis, which enables cells to swim towards favorable chemical habitats. Increase in the viscous resistance to the rotation of the motor (mechanical load) inhibits switching. However, cells must maintain homeostasis in switching to navigate within environments of different viscosities. The mechanism by which the cell maintains optimal chemotactic function under varying loads is not understood. Here, we show that the flagellar motor allosterically controls the binding affinity of the chemotaxis response regulator, CheY-P, to the flagellar switch complex by modulating the mechanical forces acting on the rotor. Mechanosensitive CheY-P binding compensates for the load-induced loss of switching by precisely adapting the switch response to a mechanical stimulus. The interplay between mechanical forces and CheY-P binding tunes the chemotactic function to match the load. This adaptive response of the chemotaxis output to mechanical stimuli resembles the proprioceptive feedback in the neuromuscular systems of insects and vertebrates.
Liquid state properties and solidification features of the pseudo binary BaS-La2S3
Authors: Boury Charles , Allanore Antoine
Published: September 2021

The high temperature thermodynamic properties of chalcogenides materials based on BaS remain elusive. Herein the pseudo binary BaS-La2S3 is investigated above 1573 K. The liquid properties of BaS-La2S3 are measured by means of high resolution in-situ visualization coupled with thermal arrest measurements in a thermal imaging furnace. This enables to report the first observation of such melts in a container-less setting. The melting points of BaS and La2S3 are revisited at 2454 K and 2004 K respectively. La2S3 demonstrates a high stability in its liquid state, in strike difference with the sublimation observed for BaS. BaS is however partially stabilized with the addition of few percents of La2S3. The remarkable chemical and thermal stability of La2S3-rich samples contrasts with the partial decomposition and high vapor pressure observed for BaS-rich samples. Observations and analysis of the solidified samples suggest three different solid solutions. Solid and liquid densities are investigated along the different compositions, supporting a first estimate of the volumetric thermal expansion coefficient for La2S3.