bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACKR3–arrestin2/3 complexes reveal molecular consequences of GRK-dependent barcoding
Authors: Chen Qiuyan , Schafer Christopher T. , Mukherjee Somnath , Gustavsson Martin , Agrawal Parth , Yao Xin-Qiu , Kossiakoff Anthony A. , Handel Tracy M. , Tesmer John J. G. 
Published: July 2023

SUMMARYAtypical chemokine receptor 3 (ACKR3, also known as CXCR7) is a scavenger receptor that regulates extracellular levels of the chemokine CXCL12 to maintain responsiveness of its partner, the G protein-coupled receptor (GPCR), CXCR4. ACKR3 is notable because it does not couple to G proteins and instead is completely biased towards arrestins. Our previous studies revealed that GRK2 and GRK5 install distinct distributions of phosphates (or “barcodes”) on the ACKR3 carboxy terminal tail, but how these unique barcodes drive different cellular outcomes is not understood. It is also not known if arrestin2 (Arr2) and 3 (Arr3) bind to these barcodes in distinct ways. Here we report cryo-electron microscopy structures of Arr2 and Arr3 in complex with ACKR3 phosphorylated by either GRK2 or GRK5. Unexpectedly, the finger loops of Arr2 and 3 directly insert into the detergent/membrane instead of the transmembrane core of ACKR3, in contrast to previously reported “core” GPCR–arrestin complexes. The distance between the phosphorylation barcode and the receptor transmembrane core regulates the interaction mode of arrestin, alternating between a tighter complex for GRK5 sites and heterogenous primarily “tail only” complexes for GRK2 sites. Arr2 and 3 bind at different angles relative to the core of ACKR3, likely due to differences in membrane/micelle anchoring at their C-edge loops. Our structural investigations were facilitated by Fab7, a novel Fab that binds both Arr2 and 3 in their activated states irrespective of receptor or phosphorylation status, rendering it a potentially useful tool to aid structure determination of any native GPCR–arrestin complex. The structures provide unprecedented insight into how different phosphorylation barcodes and arrestin isoforms can globally affect the configuration of receptor–arrestin complexes. These differences may promote unique downstream intracellular interactions and cellular responses. Our structures also suggest that the 100% bias of ACKR3 for arrestins is driven by the ability of arrestins, but not G proteins, to bind GRK-phosphorylated ACKR3 even when excluded from the receptor cytoplasmic binding pocket.
The activator domain of bacterial collagenases drives collagen recognition, unwinding and processing
Authors: Serwanja Jamil , Wieland Alexander C. , Haubenhofer Astrid , Brandstetter Hans , Schönauer Esther 
Published: July 2023

AbstractCollagens form the resilient backbone of the extracellular matrix in mammals. Only few proteases are able to digest triple-helical collagen. Clostridial collagenases can efficiently process collagen. However, little is known about the mechanism of bacterial collagenolysis of either soluble collagen or the multi-hierarchically assembled, insoluble collagen fibers. Here we present a functional analysis of the distinct roles of the individual domains of collagenase G (ColG) fromHathewaya histolytica.A broad array of biochemical, biophysical, and enzymatic data consistently revealed unexpected synergistic and antagonistic interactions between the activator, peptidase and collagen-binding domains. We found the non-catalytic activator domain to act as a master regulator, coordinating the complex interactions to specifically recognize and process the diverse physiological substrates. The results presented here enable multiple applications such as the engineering of collagenase variants with selectivity for defined substrate states.
Sperm induction of somatic cell-cell fusion as a novel functional test
Authors: Brukman Nicolas G. , Valansi Clari , Podbilewicz Benjamin 
Published: July 2023

SummaryThe fusion of mammalian gametes requires the interaction between IZUMO1 on the sperm and JUNO on the oocyte. We have recently shown that ectopic expression of mouse IZUMO1 induces cell-cell fusion and that sperm can fuse to fibroblasts expressing JUNO. Here, we found that the incubation of mouse sperm with hamster fibroblasts or human epithelial cells in culture induces the fusion between these somatic cells and formation of syncytia, a pattern previously observed with some animal viruses. This sperm-induced cell-cell fusion requires a species-matching JUNO on both fusing cells, can be blocked by an antibody against IZUMO1, and does not rely on the synthesis of new proteins. The fusion is dependent on the sperm’s fusogenic capacity, making this a reliable, fast and simple method for predicting sperm function during the diagnosis of male infertility.HighlightsSperm induces viral-like fusion of somatic cells expressing JUNOWe developed a new technique to determine the fertilization potential of spermThe test measures the capacity of sperm to induce somatic cell fusionThe degree of somatic cell fusion correlates with the fertilizing ability of spermGraphical abstract
Wild edible yams from Madagascar: New insights into nutritional composition support their use for food security and conservation
Authors: Ratsimbazafy Mirana K. , Sharp Paul A. , Razanamparany Louisette , Rajaonah Mamy Tiana , Rakotoarison Feno , Khoja Kholoud K. , Wilkin Paul , Howes Melanie-Jayne R. 
Published: July 2023

AbstractYams (Dioscoreaspecies) are an important food resource in Madagascar, where both cultivated winged yam (D. alata) and wild edible yams are consumed. However, there is limited knowledge on the nutrient composition of wild edible yams in Madagascar, and on how they compare with the cultivated winged yam. Therefore, in this study, nine wild edible yam species, one with two subspecies from Madagascar (D. bako,D. buckleyana,D. irodensis,D. maciba,D. orangeana,D. pteropoda,D. sambiranensissubsp.bardotiaeand subsp.sambiranensis,D. serifloraandDioscoreaspecies Ovy valiha), were analysed for their nutrient composition, compared with cultivatedD. alata. They include 6/6 of the most favoured wild edible yam species in Madagascar. We present new nutrient composition data (protein, carbohydrate/starch, energy, lipid, β-carotene, minerals) for these nine wild edible yam species and show that they contain comparable levels of lipids and starch toD. alata, but none are better sources of protein thanD. alata. We show thatD. irodensiscontains a significantly higher β-carotene content when compared to all other edible yams analysed, and thatD. buckleyana,D. irodensisandD. sambiranensissubsp.bardotiaehave a higher calcium content than cultivatedD. alata, while all nine wild edible yam species analysed contain a higher iron content, compared to cultivatedD. alata. The nutrient composition data presented could provide new incentives to conserve wild edible yams and inform on strategies to selectDisocoreaspecies for sustainable cultivation and use, providing opportunities to enhance future food security in Madagascar.
Education to secure empire and self-government: civics textbooks in Australia and Aotearoa, New Zealand, from 1880 to 1920
Authors: Kusabs Julian Rawiri 
Published: July 2023

PurposeRecent trends in Western civics education have attempted to secure democratic institutions from perceived threats. This paper investigates how political securitisation historically operated within civics textbooks in Australia and Aotearoa, New Zealand. It further evaluates how Māori, Aboriginal and other Indigenous peoples were variably incorporated or marginalised in these educational discourses.Design/methodology/approachThis discourse analysis evaluates a sample of civics textbooks circulated in Australia and New Zealand between 1880 and 1920. These historical sources are interpreted through theories of decoloniality and securitisation.FindingsThe sample of textbooks asserted to students that their self-governing colonies required the military protection of the British Empire against undemocratic “threats”. They argued that self-governing colonies strengthened the empire by raising subjects who were loyal to British military interests and ideological values. The authors pedagogically encouraged a governmentality within students that was complementary to military, imperial and democratic service. The hypocritical denial of self-government for many Indigenous peoples was rationalised as a measure of “security” against “native rule” and imperial rivals.Originality/valueUnder a lens of securitisation, the discursive links between imperialism, military service and democratic diligence have not yet been examined in civics textbooks from the historical contexts of Australia and New Zealand. This investigation provides conceptual and pedagogical insights for contemporary civics education in both nations.
Organisational culture and information security awareness of Chinese grassroots civil servants: A mediated moderation model
Authors: Chen Lin , Zhen Jie , Dong Kunxiang , Xie Zongxiao 
Published: July 2023

AbstractDigital information and data significantly improve the efficiency of government work in China. At the same time, in order to deal with information security and data leakage events, public departments have begun to pay attention to the information security awareness and behaviour of civil servants. Based on organisational culture and protection motivation theory, this study constructed a mediated moderation model to explore the influence mechanism of grassroots civil servants’ awareness of information security. This study collected 324 questionnaires from four regions of China. Results show that organisational culture has a significant positive impact on information security awareness. Professional identity has a significant positive effect on public service motivation and plays a negative moderating role in the relationship between organisational culture and information security awareness. Public service motivation mediates the moderating effect of professional identity on the relationship between organisational culture and information security awareness. The findings of this study offer practical implications and suggestions for further research.Points for practitioners
The construction of organisational culture will effectively enhance the information security awareness of Chinese grassroots civil servants.
Public departments should consider professional identity as an important factor when selecting grassroots civil servants engaged in information security work.
In the implementation of information security management strategy planning, government departments can pay attention to and emphasise the public service motivation of grassroots civil servants.
Effect of SHR0302 on the pharmacokinetics of CYP3A4, CYP2C8, CYP2C9 and CYP2C19 probe substrates in healthy volunteers: A cocktail analysis
Authors: Fu Meng , Luo Lin , Feng Sheng , Lin Hongda , Lu Zekun , Gu Fei , Fan Yang , Wu Bing , Huang Jianying , Shen Kai 
Published: July 2023

AbstractAimsThis study evaluated the effects of SHR0302 on the pharmacokinetics of cytochrome P450 (CYP) probe substrates.MethodsWe performed a single‐centre, open‐label, three‐period drug–drug interaction (DDI) study in 24 healthy subjects (NCT05392127). Subjects received a single oral dose of 5 mg warfarin (CYP2C9), 20 mg omeprazole (CYP2C19) and 15 mg midazolam (CYP3A4) on Days 1, 8 and 22, and received 0.5 mg repaglinide (CYP2C8) on Days 7, 14 and 28. Multiple oral doses of 8 mg SHR0302 were administered once daily from Day 8 to Day 28.ResultsThe exposure of S‐warfarin and repaglinide were comparable before and after SHR0302 administration. AUC of midazolam was not affected by SHR0302, whereas the administration of SHR0302 slightly decreased the Cmax of midazolam by 7.6% (single dose) and 15.7% (once daily for 14 days). The AUC0‐t, AUC0‐inf, and Cmax of omeprazole were slightly decreased after a single dose of SHR0302 by 19.2%, 21.8% and 23.5%, respectively. In the presence of SHR0302 for 14 days, the AUC0‐t, AUC0‐inf, and Cmax of omeprazole were marginally reduced by 3.0%, 16.4% and 8.3%, respectively. According to the induction mechanism of the CYP enzyme, for the investigation of the induction effect, the results of multiple administrations of the perpetrator were more reliable than those of the single dose.ConclusionsThe results demonstrated that co‐administration of SHR0302 8 mg once daily is unlikely to have a clinically meaningful effect on the exposure of drugs metabolized by CYP3A4, CYP2C8, CYP2C9 and CYP2C19 in healthy subjects.
How can aid be decolonized and localized in the Pacific? Yielding and wielding power
Authors: Meki Theresa , Tarai Jope 
Published: July 2023

AbstractMotivationThe colonial legacies of aid and development in the Pacific continue to be at the centre of policy debate. The ideal is to decolonize and localize the practice of aid and development. However, decolonization and localization have become highly contested in their definition and proposed practical approaches. We call decolonization and localization “decolocalization.”PurposeThis article aims to explore perspectives and proposals for decolocalization in the Pacific Islands.Methods and approachWe talked to five key informants, all local to their islands, all with considerable development experience; we held a focus group; and we combined these insights and learnings with our own experience as Pacific Islanders engaged with development. Our analysis is reflexive.FindingsDevelopment practice in the Pacific Islands typically overvalues external Euro‐centric knowledge and undervalues local knowledge. Most aid and development discourse has stressed financial figures, charts, and statistical assertions overwhelmingly from a donor perspective; Pacific non‐statistical, human, and embodied contextual realities are overlooked or discounted. Hierarchies are created that privilege outsiders and discriminate against islanders.A practical operationalization of decolocalization can begin with the recognition and practice of outsiders yielding and insiders wielding power.Policy implicationsWe recommend decolocalization as a framework for studying and analysing colonial vestiges in Pacific aid and development. Decolocalization can be practised by outsiders yielding and insiders wielding power in aid and development.Decolocalization is not an ultimate solution to a highly complex issue, but it offers a conceptual position; one that allows Pacific Islander scholars, thought leaders, and aid and development practitioners to further unpack the nuances and issues around aid and development from a Pacific Islander perspective.
Institutional investors and corporate environmental costs: The roles of investment horizon and investor origin
Authors: Drobetz Wolfgang , El Ghoul Sadok , Fu Zhengwei , Guedhami Omrane 
Published: July 2023

AbstractUsing an international data set that quantifies corporate environmental costs, we analyze the influence of institutional investor ownership, particularly investment horizon and investor origin, on the monetized environmental impact generated by their investee firms. Institutional investor ownership is negatively related to corporate environmental costs. This effect is driven by long‐term foreign institutional investors, especially investors from advanced economies. Corporate environmental costs are negatively correlated with firm valuation and positively correlated with the cost of equity. Since corporate environmental costs are not reflected in environmental, social and governance ratings, our results shed new light on the role of institutional investors in shaping corporate environmental impact.
The effect of mass media campaigns on oral health knowledge: A systematic review and meta‐analysis
Authors: Banakar Morteza , Lankarani K. B. , Vali Mohebat , Tabrizi Reza , Taherifard Erfan , Akbari Maryam 
Published: July 2023

AbstractObjectivesKnowledge and awareness gained from mass media can prepare people for lifestyle changes and impact their health and well‐being. Considering the differences in the results of primary studies, we decided to conduct this study to evaluate the effect of mass media campaigns on oral health knowledge as a systematic meta‐analysis and review.MethodThe databases such as the Web of Sciences (ISI), Scopus, PubMed/Medline, and the Cochrane Library were searched systematically until February 2022. Data pooling was performed using a random effects model. The effect sizes were estimated as odds ratios (ORs) with their 95% confidence intervals (CIs). Additional analyses, including sensitivity, subgroup, and publication bias analyses, were also conducted.ResultsOur meta‐analysis comprised a total number of seven articles. The pooled results indicated significant increases in oral health knowledge among included studies (OR = 1.64, 95% CI: 1.20–2.24, p < 0.001). In subgroup analyses, the effects of mass media campaigns on oral health knowledge remained significant for the studies with follow‐up of less than 150 weeks (OR = 1.69, 95% CI: 1.49–1.91) and working‐age populations (OR = 1.80, 95% CI: 1.40–2.32) compared to other categories.ConclusionIn general, this study showed that mass media campaigns may have positive effects on oral health knowledge, especially in the working‐age population; it seems that for improving health knowledge among children, more initiatives are needed. Besides, the effects of these campaigns seem to be time‐dependent and higher in shorter follow‐up periods.
Periradicular tissue fluid‐derived biomarkers for apical periodontitis: An in vitro methodological and in vivo cross‐sectional study
Authors: Virdee Satnam S. , Bashir Nasir Z. , Krstic Milan , Camilleri Josette , Grant Melissa M. , Cooper Paul R. , Tomson Phillip L. 
Published: July 2023

AbstractBackgroundPeriradicular tissue fluid (PTF) offers a source of diagnostic, prognostic and predictive biomarkers for endodontic disease.Aims(1) To optimize basic parameters for PTF paper point sampling in vitro for subsequent in vivo application. (2) To compare proteomes of PTF from teeth with normal apical tissues (NAT) and asymptomatic apical periodontitis (AAP) using high‐throughput panels.Methodology(1) To assess volume absorbance, paper points (n = 20) of multiple brands, sizes and sampling durations were inserted into PBS/1%BSA at several depths. Wetted lengths (mm) were measured against standard curves to determine volume absorbance (μL). To assess analyte recovery, paper points (n = 6) loaded with 2 μL recombinant IL‐1β (15.6 ng/mL) were eluted into 250 μL: (i) PBS; (ii) PBS/1% BSA; (iii) PBS/0.1% Tween20; (iv) PBS/0.25 M NaCl. These then underwent: (i) vortexing; (ii) vortexing/centrifugation; (iii) centrifugation; (iv) incubation/vortexing/centrifugation. Sandwich‐ELISAs determined analyte recovery (%) against positive controls.(2) Using optimized protocols, PTF was retrieved from permanent teeth with NAT or AAP after accessing root canals. Samples, normalized to total fluid volume (TFV), were analysed to determine proteomic profiles (pg/TFV) of NAT and AAP via O‐link Target‐48 panel. Correlations between AAP and diagnostic accuracy were explored using principal‐component analysis (PCA) and area under receive‐operating‐characteristic curves (AUC [95% CI]), respectively. Statistical comparisons were made using Mann–Whitney U, anova and post hoc Bonferonni tests (α < .01).Results(1) UnoDent's ‘Classic’ points facilitated maximum volume absorbance (p < .05), with no significant differences after 60 s (1.6 μL [1.30–1.73]), 1 mm depth and up to 40/0.02 (2.2 μL [1.98–2.20]). For elution, vortexing (89.3%) and PBS/1% BSA (86.9%) yielded the largest IL‐1β recovery (p < .05).(2) 41 (NAT: 13; AAP: 31) PTF samples proceeded to analysis. The panel detected 18 analytes (CCL‐2, ‐3, ‐4; CSF‐1; CXCL‐8, ‐9; HGF; IL‐1β, ‐6, ‐17A, ‐18; MMP‐1, ‐12; OLR‐1; OSM; TNFSF‐10, ‐12; VEGF‐A) in ≥75% of AAP samples at statistically higher concentrations (p < .01). CXCL‐8, IL‐1β, OLR‐1, OSM and TNFSF‐12 were strongly correlated to AAP. ‘Excellent’ diagnostic performance was observed for TNFSF‐12 (AUC: 0.94 [95% CI: 0.86–1.00]) and the PCA‐derived cluster (AUC: 0.96 [95% CI: 0.89–1.00]).ConclusionsOptimized PTF sampling parameters were identified in this study. When applied clinically, high‐throughput proteomic analyses revealed complex interconnected networks of potential biomarkers. TNFSF‐12 discriminated periradicular disease from health the greatest; however, clustering analytes further improved diagnostic accuracy. Additional independent investigations are required to validate these findings.
Platelet genetic testing by next‐generation sequencing: A practical update
Authors: Chen Dong , Pruthi Rajiv K. 
Published: July 2023

AbstractInherited platelet disorders (IPDs) are a heterogeneous group of disorders characterized by normal or reduced platelet counts, bleeding diatheses of varying severities, and the presence (syndromic) or absence (non‐syndromic) of involvement of other organs. Due to the lack of highly specific platelet function tests and overlapping clinical and laboratory features, diagnosing the underlying cause of IPDs remains challenging. In recent years, genetic testing via next‐generation sequencing (NGS) technologies to rapidly analyze multiple genes has gradually emerged as an important part of the laboratory investigation of patients with IPDs. A systemic clinical and laboratory testing approach and thorough phenotype and genotype correlation studies of both patients and their family members are crucial for accurate diagnoses of IPDs.
Collection responsibility and freight insurance strategies for an e‐tailing supply chain in the presence of managerial optimism
Authors: Yu Lingfei , Xiao Tiaojun , Xu Peng 
Published: July 2023

AbstractEntrepreneurs are usually optimistic when they offer return policies. We investigate the strategic interaction between the manufacturer's collection responsibility strategy (returns handled by the manufacturer or the e‐tailer) and the e‐tailer's complimentary return‐freight insurance strategy (whether to offer this insurance or not) in the presence of managerial optimism. It is found that the manufacturer's collection responsibility strategy creates the (implicit) incentive for the e‐tailer to offer complimentary return‐freight insurance. A high level of optimism and return handling costs expand the equilibrium range over which the manufacturer collects returns, and the e‐tailer offers complimentary return‐freight insurance. Contrary to conventional wisdom, we find that unilateral optimism does not always lead to a win‐win situation, but it can still result in suboptimal results on the other side. Finally, despite possibly high shipping costs, the e‐tailer's refusal to offer complimentary return‐freight insurance still benefits consumers, implying that managers with high optimism level benefit consumers.