bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging ideas. Filial piety, substance use, adverse childhood experiences, and parental support: An intergenerational perspective
Authors: Zhao Xiang , Perle Isabella , Foran Heather M.
Published: February 2023

Objective

The goal was to test the validity of the dual filial piety model in Austria and examine how the reciprocal and authoritarian filial piety interplay with familial factors and one's tobacco and alcohol use.

Background

Familial influences on substance use have been identified. Being conceptualized as a Chinese construct, research on filial piety and its interplay with substance use is insufficient in Western populations.

Method

Using a cross‐sectional survey including filial piety, familial variables, psychopathy traits, and alcohol use, we collected data from 201 Austrian community members (63.0% female; Mage = 35.15 years). Another age‐stratified random sample with 202 Austrians was also subsequently recruited to replicate the original findings. Multiple correlational analyses and confirmatory structural equation modeling were utilized on both samples, separately.

Results

The dual filial piety model was found as a robust construct in both samples, with an acceptable scalability (Cronbach's α > .70). Although filial piety was unassociated with substance use, earlier experiences and psychopathy traits both showed consistent correlations with substance use. Un‐directional network analysis among variables further revealed an association between ever smoking experience and adverse childhood experiences, which was replicated in the second sample.

Conclusions

This study highlights the utility of filial piety in non‐Eastern populations. Filial piety was associated with substance use in one sample, but more research from family and developmental psychology is needed given its close relationships with childhood aversive experiences and remembered parental support.
Temperature, productivity, and habitat characteristics collectively drive lake food web structure
Authors: Leclerc Camille , Reynaud Nathalie , Danis Pierre‐Alain , Moatar Florentina , Daufresne Martin , Argillier Christine , Usseglio‐Polatera Philippe , Verneaux Valérie , Dedieu Nicolas , Frossard Victor , Sentis Arnaud
Published: February 2023

While many efforts have been devoted to understand variations in food web structure among terrestrial and aquatic ecosystems, the environmental factors influencing food web structure at large spatial scales remain hardly explored. Here, we compiled biodiversity inventories to infer food web structure of 67 French lakes using an allometric niche‐based model and tested how environmental variables (temperature, productivity, and habitat) influence them. By applying a multivariate analysis on 20 metrics of food web topology, we found that food web structural variations are represented by two distinct complementary and independent structural descriptors. The first is related to the overall trophic diversity, whereas the second is related to the vertical structure. Interestingly, the trophic diversity descriptor was mostly explained by habitat size (26.7% of total deviance explained) and habitat complexity (20.1%) followed by productivity (dissolved organic carbon: 16.4%; nitrate: 9.1%) and thermal variations (10.7%). Regarding the vertical structure descriptor, it was mostly explained by water thermal seasonality (39.0% of total deviance explained) and habitat depth (31.9%) followed by habitat complexity (8.5%) and size (5.5%) as well as annual mean temperature (5.6%). Overall, we found that temperature, productivity, and habitat characteristics collectively shape lake food web structure. We also found that intermediate levels of productivity, high levels of temperature (mean and seasonality), as well as large habitats are associated with the largest and most complex food webs. Our findings, therefore, highlight the importance of focusing on these three components especially in the context of global change, as significant structural changes in aquatic food webs could be expected under increased temperature, pollution, and habitat alterations.
Influence of dividend tax policy tied to investment horizon on stock price stability: Evidence from the 2015 dividend tax reform in China
Authors: Guo Nianzhi , Sun Ping‐Wen , Xiao Huiqin
Published: February 2023

We examine how the dividend tax cut policy tied to the investment horizon enforced on September 8, 2015, influences stock price stability in China's A‐share market. As the new dividend tax policy waives the tax on cash dividends for investors holding a stock for more than a year, it encourages long‐term investment behavior. From 2013 to 2017, we find that stock turnover, return volatility, and turnover volatility decrease after the policy enforcement, especially for stocks with high dividend yields. This result shows that dividend tax reforms increase investors' stock investment horizons and help stabilize the market. However, our findings demonstrate that stock crash risk increases after policy enforcement. Further analysis shows that earnings management through real activities manipulation for stocks with a higher dividend yield contributes to an increase in stock crash risk. Therefore, one externality of the dividend tax cut policy tied to the investment horizon is that top managers of firms with a higher dividend yield may take advantage of investors' passive longer‐term investment behavior and engage in more earnings management. This result suggests that regulatory agencies should pay attention to top managers' earnings management behavior after enacting policies that encourage long‐term investment.
Pressureless sintering of dual‐phase, high‐entropy boride–carbide ceramics
Authors: Smith Steven M. , Fahrenholtz William G. , Hilmas Greg E. , Huang Tieshu
Published: February 2023

Dual‐phase, high‐entropy boride–carbide ceramics were densified by pressureless sintering. Relative densities up to approximately 96% were obtained for ceramics containing about 30 vol% high‐entropy boride and 70 vol% high‐entropy carbide. Isostatic pressing at 200 MPa resulted in higher relative densities of both the green bodies and final ceramics compared to uniaxial pressing. The highest relative density of 96.3% was achieved for a ceramic that was isostatically pressed at 200 MPa and sintered at 2300°C for 2 h. Grain sizes of the resulting ceramics were approximately 2 µm. This is the first report of pressureless sintering of dual‐phase, high‐entropy boride–carbide ceramics.
Driving reactive nitrogen emissions in China: Competition between scale and efficiency
Authors: Huang Yunfeng , Cui Shenghui , Gao Bing , Huang Wei , Han Shuangying , Hu Yuanchao
Published: February 2023

Reactive nitrogen (Nr) emissions aggravate air and water pollution across the world. The factors influencing Nr emissions have not been clearly uncovered, especially for regions under rapid economic growth. Here we modeled total Nr emissions in mainland China and analyzed factors driving their growth during the decade (2000–2010) of fastest socioeconomic development. Results show that total Nr emissions increased from 24.9 terrogram (Tg) to 35.2 Tg, a 41.7% increase with an average annual growth rate of 3.5%. Agricultural activities, including crop planting and livestock and poultry breeding, together took a substantial but decreasing share, from 75.2% in 2000 to 61.4% in 2010. Industrial wastewater discharge, energy use, and crop production are the three largest sources contributing to the Nr emissions growth. Factors related to scale (e.g., the amount of industrial energy use) led to a growth in Nr emissions, and factors related to efficiency (e.g., industrial energy use per unit of economic output) contributed to reduction. The decreasing effect of efficiency gains, however, was still unable to overcome the increasing effect of the activity scale. More in‐depth research studies on mitigation strategies are required, to inform the decoupling between socioeconomic development and Nr emissions.
The β‐adrenergic hypothesis of synaptic and microglial impairment in Alzheimer's disease
Authors: Li Shaomin
Published: February 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disease originating partly from amyloid β protein‐induced synaptic failure. As damaging of noradrenergic neurons in the locus coeruleus (LC) occurs at the prodromal stage of AD, activation of adrenergic receptors could serve as the first line of defense against the onset of the disease. Activation of β2‐ARs strengthens long‐term potentiation (LTP) and synaptic activity, thus improving learning and memory. Physical stimulation of animals exposed to an enriched environment (EE) leads to the activation of β2‐ARs and prevents synaptic dysfunction. EE also suppresses neuroinflammation, suggesting that β2‐AR agonists may play a neuroprotective role. The β2‐AR agonists used for respiratory diseases have been shown to have an anti‐inflammatory effect. Epidemiological studies further support the beneficial effects of β2‐AR agonists on several neurodegenerative diseases. Thus, I propose that β2‐AR agonists may provide therapeutic value in combination with novel treatments for AD.

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MED13L and its disease‐associated variants influence the dendritic development of cerebral cortical neurons in the mammalian brain
Authors: Hamada Nanako , Iwamoto Ikuko , Nagata Koh‐ichi
Published: February 2023

The mediator complex comprises multiple subcellular subunits that collectively function as a molecular interface between RNA polymerase II and gene‐specific transcription factors. Recently, genetic variants to one subunit of the complex, known as MED13L (mediator complex subunit 13 like), have been implicated in syndromic intellectual disability and distinct facial features, frequently accompanied by congenital heart defects. We investigated the impact of five disease‐associated MED13L variants on the subcellular localization and biochemical stability of MED13L protein in vitro and in vivo. In overexpression assays using cortical neurons from embryonic mouse cerebral cortices transduced by in utero electroporation‐mediated gene transfer, we found that mouse orthologues of human MED13L‐p.P866L and ‐p.T2162M missense variants accumulated in the nucleus, while the p.S2163L and p.S2177Y variants were diffusely distributed in the cytoplasm. In contrast, we found that the p.Q1922* truncation variant was barely detectable in transduced cells, a phenotype reminiscent of this variant that results in MED13L haploinsufficiency in humans. Next, we analyzed these variants for their effects on neuronal migration, dendritic growth, spine morphology, and axon elongation of cortical neurons in vivo. There, we found that overexpression of the p.P866L variant resulted in reduced number and length of dendrites of cortical layer II/III pyramidal neurons. Furthermore, we show that mMED13L‐knockdown abrogated dendritic growth in vivo, and this effect was significantly rescued by co‐electroporation of an RNAi‐resistant mMED13L, but weakly by the p.T2162M variant, and not at all by the p.S2163L variant. However, overexpression of the p.S2163L variant inhibited mature dendritic spine formation in vivo. Expression of each of the 5 variants did not affect neuronal cell migration and callosal axon elongation in vivo. Taken together, our results demonstrate that MED13L expression is relevant to corticogenesis and influences the dendritic branching characteristics of cortical excitatory neurons. Our study also suggests that disease‐associated MED13L variants may directly cause morphological and functional defects in cortical neurons in different ways.

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The impact of the global COVID‐19 pandemic on risk factors for suicide in healthcare workers: A narrative review
Authors: Zohn Jennifer H. , Hovis Sophia
Published: February 2023

Background

Suicide is a leading cause of death in the United States. Worldwide, over 700,000 people die by suicide each year. Healthcare workers are more vulnerable to suicide risk factors than the general population. The global COVID‐19 pandemic presents additional workplace and health concerns that relate to suicide risk factors in healthcare workers. It is important to recognise suicide risk factors in healthcare workers and to implement strategies to reduce these risk factors.

Objectives

This study describes the impact of the global COVID‐19 pandemic on risk factors for suicide in healthcare workers and identifies evidence‐based strategies and resources to reduce suicide risk factors in healthcare workers.

Design

The authors conducted a thematic analysis and narrative review of the literature.

Methods

Using health science databases, the authors searched the literature, selected and analyzed studies, identified themes, synthesised findings and created a narrative review. The STROBE checklist was used in this study.

Results

Two themes were identified (1) The impact of the COVID‐19 pandemic on work‐related suicide risk factors in healthcare workers; (2) The impact of the COVID‐19 pandemic on mental health‐related suicide risk factors in healthcare workers. The pandemic has affected suicide risk factors in healthcare workers. Many studies discussed evidence‐based strategies and resources that can be used to reduce suicide risk factors.

Conclusion

The global COVID‐19 pandemic has negatively impacted suicide risk factors in healthcare workers. It is time for individuals and healthcare delivery systems to implement suicide risk prevention strategies to protect healthcare workers now and in the future.

Relevance to Clinical Practice

This review increases awareness of the pandemic's impact on healthcare workers' risk factors for suicide and identifies evidence‐based suicide risk prevention strategies and resources for healthcare workers.

Patient or Public Contribution

Library services supported this research by generating search strategies and providing resources and tools.
How Does CEO Decision Style Influence Firm Performance? The Mediating Role of Speed and Innovativeness in New Product Development
Authors: Kruse Sebastian , Bendig David , Brettel Malte
Published: February 2023

Although chief executive officers (CEOs) are the primary decision‐makers in their firms, there has been little research on how CEOs' decision styles affect firm performance. This study explores the relationships between firm performance and two key dimensions of CEO decision style, namely the use of heuristics and decision standards. We conceptualize the speed and innovativeness of new product development (NPD) as mediators in these relationships. An empirical analysis of 1046 German firms indicates that CEOs' use of heuristics may lead to higher NPD speed and stronger firm performance. In addition, higher decision standards, i.e., a stronger tendency to make the best decisions possible, among CEOs may promote higher NPD speed, NPD innovativeness, and firm performance but may also lead to less use of heuristics. Our findings underscore the relevance of CEO decision styles for firm performance and NPD, contribute to the debate on the rationality of heuristics, and conceptually broaden the role of decision standards in decision‐making.
The inhibition and recovery mechanisms of the diatom Phaeodactylum tricornutum in response to high light stress – A study combining physiological and transcriptional analysis
Authors: Kan Chengxiang , Zhao Yirong , Sun Kai‐Ming , Tang Xuexi , Zhao Yan
Published: February 2023

By combining physiological/biochemical and transcriptional analysis, the inhibition and recovery mechanisms of Phaeodactylum tricornutum in response to extreme high light stress (1300 μmol photons · m−2 · s−1) were elucidated. The population growth was inhibited in the first 24 h and started to recover from 48 h. At 24 h, photoinhibition was exhibited as the changes of PSII photosynthetic parameters and decrease in cellular pigments, corresponding to the downregulation of genes encoding light‐harvesting complex and pigments synthesis. Changes in those photosynthetic parameters and genes were kept until 96 h, indicating that the decrease of light absorption abilities might be one strategy for photoacclimation. In the meanwhile, we observed elevated cellular ROS levels, dead cells proportions, and upregulation of genes encoding antioxidant materials and proteasome pathway at 24 h. Those stress‐related parameters and genes recovered to the controls at 96 h, indicating a stable intracellular environment after photoacclimation. Finally, genes involving carbon metabolisms were upregulated from 24 to 96 h, which ensured the energy supply for keeping high base and nucleotide excision repair abilities, leading to the recovery of cell cycle progression. We concluded that P. tricornutum could overcome photoinhibition by decreasing light‐harvesting abilities, enhancing carbon metabolisms, activating anti‐oxidative functions, and elevating repair abilities. The parameters of light harvesting, carbon metabolisms, and repair processes were responsible for the recovery phase, which could be considered long‐term adaptive strategies for diatoms under high light stress.
The deepening of the Pacific Alliance's commercial agenda: The role of policy networks in regulatory governance
Authors: Castro‐Silva Julissa
Published: February 2023

From a complementary perspective to intergovernmental approaches, this article emphasizes the seldom explored role of policy networks in regional regulatory governance to explain the factors that have enhanced or limited the deepening of the Pacific Alliance's trade agenda 10 years after its launch. Within a context of a proliferation of trade agreements in Latin America, but with limited knowledge about their regulation since there are no developed countries in the agreement, it is argued that the horizontal dynamics of interaction established by trans‐governmental and transnational networks, as well as the greater articulation among them, have facilitated the deepening of a mutual working scheme. By contrast, the vertical interaction dynamics associated with a North–South economic pattern between Mexico and the other members of the bloc have placed limits on the model of deep integration designed by the group. This article is based on a multiple case study that uses process tracing to consider a process observed from the Global South, considering its particularities and overcoming state‐centric visions. Desde una perspectiva complementaria a los enfoques intergubernamentales, este trabajo enfatiza el poco explorado papel de las redes políticas en la gobernanza regulatoria regional para explicar los factores que han potenciado o limitado la profundización de la agenda comercial de la Alianza del Pacífico a diez años de su lanzamiento. En un contexto de proliferación de acuerdos comerciales en América Latina, pero de limitado conocimiento sobre su regulación en ausencia de países desarrollados, se argumenta que las dinámicas horizontales de interacción establecidas por las redes transgubernamentales y transnacionales, así como la mayor articulación entre éstas, han facilitado la profundización de un esquema de trabajo propio. En cambio, las dinámicas verticales de interacción asociadas a un patrón económico Norte–Sur entre México y los demás miembros del bloque han puesto límites al modelo de integración profunda diseñado por el grupo. Este artículo se basa en un estudio de casos múltiples que utiliza el rastreo de procesos para abordar un proceso que es observado desde el Sur Global, atendiendo sus particularidades y superando visiones estado‐céntricas.
Insoluble macromolecular organic matter in the Winchcombe meteorite
Authors: Sephton Mark A. , Chan Queenie H. S. , Watson Jonathan S. , Burchell Mark J. , Spathis Vassilia , Grady Monica M. , Verchovsky Alexander B. , Abernethy Feargus A. J. , Franchi Ian A.
Published: February 2023

The Winchcombe meteorite fell on February 28, 2021 in Gloucestershire, United Kingdom. As the most accurately recorded carbonaceous chondrite fall, the Winchcombe meteorite represents an opportunity to link a tangible sample of known chemical constitution to a specific region of the solar system whose chemistry can only be otherwise predicted or observed remotely. Winchcombe is a CM carbonaceous chondrite, a group known for their rich and varied abiotic organic chemistry. The rapid collection of Winchcombe provides an opportunity to study a relatively terrestrial contaminant‐limited meteoritic organic assemblage. The majority of the organic matter in CM chondrites is macromolecular in nature and we have performed nondestructive and destructive analyses of Winchcombe by Raman spectroscopy, online pyrolysis–gas chromatography–mass spectrometry (pyrolysis–GC–MS), and stepped combustion. The Winchcombe pyrolysis products were consistent with a CM chondrite, namely aromatic and polycyclic aromatic hydrocarbons, sulfur‐containing units including thiophenes, oxygen‐containing units such as phenols and furans, and nitrogen‐containing units such as pyridine; many substituted/alkylated forms of these units were also present. The presence of phenols in the online pyrolysis products indicated only limited influence from aqueous alteration, which can deplete the phenol precursors in the macromolecule when aqueous alteration is extensive. Raman spectroscopy and stepped combustion also generated responses consistent with a CM chondrite. The pyrolysis–GC–MS data are likely to reflect the more labile and thermally sensitive portions of the macromolecular materials while the Raman and stepped combustion data will also reflect the more refractory and nonpyrolyzable component; hence, we accessed the complete macromolecular fraction of the recently fallen Winchcombe meteorite and revealed a chemical constitution that is similar to other meteorites of the CM group.
PDZ‐binding kinase inhibitor OTS514 suppresses the proliferation of oral squamous carcinoma cells
Authors: Kato Mikako , Ota Akinobu , Ono Takayuki , Karnan Sivasundaram , Hyodo Toshinori , Rahman Md Lutfur , Hasan Muhammad Nazmul , Onda Maho , Kondo Sayuri , Ito Kunihiro , Furuhashi Akifumi , Hayashi Tomio , Konishi Hiroyuki , Tsuzuki Shinobu , Hosokawa Yoshitaka , Kazaoka Yoshiaki
Published: February 2023

Objective

PDZ‐binding kinase (PBK) has been reported as a poor prognostic factor and is a promising molecular target for anticancer therapeutics. Here, we aimed to investigate the effect of specific PBK inhibitor OTS514 on the survival of OSCC cells.

Methods

Four OSCC cell lines (HSC‐2, HSC‐3, SAS, and OSC‐19) were used to examine the effect of OTS514 on cell survival and apoptosis. DNA microarray analysis was conducted to investigate the effect of OTS514 on gene expression in OSCC cells. Gene set enrichment analysis was performed to identify molecular signatures related to the antiproliferative effect of OTS514.

Results

OTS514 decreased the cell survival of OSCC cells dose‐dependently, and administration of OTS514 readily suppressed the HSC‐2‐derived tumor growth in immunodeficient mice. Treatment with OTS514 significantly increased the number of apoptotic cells and caspase‐3/7 activity. Importantly, OTS514 suppressed the expression of E2F target genes with a marked decrease in protein levels of E2F1, a transcriptional factor. Moreover, TP53 knockdown attenuated OTS514‐induced apoptosis.

Conclusion

OTS514 suppressed the proliferation of OSCC cells by downregulating the expression of E2F target genes and induced apoptosis by mediating the p53 signaling pathway. These results highlight the clinical application of PBK inhibitors in the development of molecular‐targeted therapeutics against OSCC.
Success with a twinge of distress: Antecedents and consequences of outperformance‐related discomfort
Authors: Koch Erika J.
Published: February 2023

Although outperforming others brings intrapersonal benefits, it may also carry interpersonal costs. The term Sensitivity about being the Target of a Threatening Upward Comparison (STTUC) captures the discomfort that outperformers may feel when they perceive that their success upsets an outperformed person. This paper reviews 20+ years of research on STTUC. It begins by defining STTUC and its three essential criteria. It then delineates situation and person variables that explain variability in STTUC. It follows by describing outperformers' varied reactions to STTUC and then explains the potential social function of STTUC.
Miocene ductile thinning below the Folegandros Detachment System, Cyclades, Greece
Authors: Bakowsky C. , Schneider D.A. , Grasemann B. , Soukis K.
Published: February 2023

Folegandros island lies between the established SW‐directed West Cycladic and S‐directed Santorini detachment systems. Preserving shear‐sense indicators with opposing kinematics, the geodynamics and timing of kinematics are debated. Using white mica 40Ar/39Ar geochronology complemented by structural data, we report a new Miocene top‐to‐S detachment system, the Folegandros Detachment System (FDS), that is coupled with pure‐shear flattening and juxtaposes the Cycladic Blueschist Unit below Early Cretaceous to early Eocene low‐grade marble and quartzitic‐phyllitic sequences, topped by a metaflysch. Chronostratigraphic correlation and detrital zircon geochronology reveal the low‐grade rocks from the hanging wall of the FDS likely belong to the Pelagonian Zone. Middle Miocene zircon and apatite (U‐Th)/He cooling ages correspond to the latest stages of exhumation. Observations of opposing kinematics on Sikinos, Ios and now Folegandros reveal that ductile thinning played a more significant role in accommodating Miocene exhumation of high‐pressure rocks in the southern Cyclades than previously postulated.
Motivations for blood donation by HIV‐positive individuals on antiretrovirals in South Africa: A qualitative study
Authors: van den Berg Karin , Murphy Edward L. , Louw Vernon J. , Maartens Gary , Hughes Shana D.
Published: February 2023

Objectives

We performed a mixed‐methods study to explore the motivations associated with blood donation by donors with known, but undisclosed HIV‐positive status and ARV use (HIV+/ARV+), seeking potential strategies to reduce such donations and mitigate risk for blood recipients. Here, we report predominantly the qualitative component.

Background

A safe and sustainable blood supply is dependent in part, on effective pre‐donation donor assessment. We previously described failure by HIV+/ARV+ blood donors to disclose their status. Such donations may lead to transfusion‐transmitted HIV.

Methods

The social ecological model provided the conceptual framework for this study. Previously identified HIV+/ARV+ donors were invited to complete a survey (including a validated stigma scale) and qualitative interview, which underwent inductive and deductive thematic analysis.

Results

We uncovered two primary motivational paths to HIV+/ARV+ blood donations: privacy and altruism. The latter included a motivation not previously reported in the literature: donating specifically for other people living with HIV (PLWH). The other primary factor was a lack of privacy. These accounts often included donors encountering donation opportunities when accompanied by people to whom they had not and did not plan to disclose their HIV status. Most were highly confident their donations would be identified as HIV‐positive and discarded.

Conclusion

We demonstrated a complex interaction between individual, social, cultural, and structural/policy factors in blood donations by PLWH who take ARV. Recommendations to limit HIV + ARV+ donations include: (1) Targeted communication strategies to increase knowledge among PLWH of their deferral from blood donation—without increasing stigma, and (2) development of procedures to assist those who feel unable to opt‐out of donation due to privacy concerns.
Puncta‐localized TRAF domain protein TC1b contributes to the autoimmunity of snc1
Authors: Ao Kevin , Rohmann Philipp F. W. , Huang Shuai , Li Lin , Lipka Volker , Chen She , Wiermer Marcel , Li Xin
Published: February 2023

Immune receptors play important roles in the perception of pathogens and initiation of immune responses in both plants and animals. Intracellular nucleotide‐binding domain leucine‐rich repeat (NLR)‐type receptors constitute a major class of receptors in vascular plants. In the Arabidopsis thaliana mutant suppressor of npr1‐1, constitutive 1 (snc1), a gain‐of‐function mutation in the NLR gene SNC1 leads to SNC1 overaccumulation and constitutive activation of defense responses. From a CRISPR/Cas9‐based reverse genetics screen in the snc1 autoimmune background, we identified that mutations in TRAF CANDIDATE 1b (TC1b), a gene encoding a protein with four tumor necrosis factor receptor‐associated factor (TRAF) domains, can suppress snc1 phenotypes. TC1b does not appear to be a general immune regulator as it is not required for defense mediated by other tested immune receptors. TC1b also does not physically associate with SNC1, affect SNC1 accumulation, or affect signaling of the downstream helper NLRs represented by ACTIVATED DISEASE RESISTANCE PROTEIN 1‐L2 (ADR1‐L2), suggesting that TC1b impacts snc1 autoimmunity in a unique way. TC1b can form oligomers and localizes to punctate structures of unknown function. The puncta localization of TC1b strictly requires its coiled‐coil (CC) domain, whereas the functionality of TC1b requires the four TRAF domains in addition to the CC. Overall, we uncovered the TRAF domain protein TC1b as a novel positive contributor to plant immunity.
Refractory shock, hypercoagulability, and multiorgan thrombosis associated with hypertrophic osteodystrophy in a dog
Authors: Perry Kayla M. , Enders Brittany D. , Negrão Watanabe Tatiane Terumi
Published: February 2023

Objective

To describe the clinical findings and case progression in a dog presenting with severe systemic inflammatory response, refractory shock, progressive metabolic acidosis, and respiratory failure that was ultimately diagnosed with hypertrophic osteodystrophy (HOD).

Case Summary

A 4‐month‐old male intact Mastiff presented with a 24‐hour history of lethargy and generalized ostealgia. On examination, the dog was recumbent, febrile, and tachycardic with pain on palpation of the abdomen, right femur, and mandible. Appendicular joint radiographs showed changes consistent with osteochondrosis and ulnar‐retained cartilaginous cores, with no overt evidence of HOD. Initial treatment included IV fluid therapy, multimodal analgesia, and broad‐spectrum antimicrobials. Vasopressor therapy was initiated following hemodynamic decompensation. Synovial fluid cytological analysis and culture revealed nonseptic suppurative inflammation and no bacterial growth, respectively. Blood and urine cultures also yielded no growth. Viscoelastic testing was consistent with hypercoagulability. The dog initially had a metabolic acidosis with appropriate respiratory compensation that progressed to a mixed metabolic and respiratory acidosis despite aggressive therapies that included antimicrobials, vasopressors, positive inotropes, and corticosteroids. Humane euthanasia was elected approximately 32 hours after admission. Necropsy yielded a diagnosis of HOD.

New or Unique Information Provided

This is the first report detailing the occurrence of refractory shock and hypercoagulability associated with HOD in a dog without evidence of another identified comorbidity. HOD should be considered in any young, large‐breed dog with generalized ostealgia and signs of systemic illness, even in the absence of classic radiographic abnormalities. Further investigation of coagulation status in dogs with HOD and a secondary systemic inflammatory response is warranted.
Duration of neuromuscular block is more variable and recovery time is shorter with rocuronium than cisatracurium in anesthetized dogs
Authors: Martin‐Flores Manuel , Hackman Megan C. , Araos Joaquin D. , Campoy Luis , Gleed Robin D.
Published: February 2023

Objective

To compare the variability in the duration of action of a single dose of rocuronium or cisatracurium, and duration of subsequent top‐up doses in anesthetized dogs.

Animals

Thirty dogs requiring ophthalmic surgery with neuromuscular block.

Procedures

Neuromuscular function was monitored with train‐of‐four (TOF) and acceleromyography. Dogs received an initial dose of rocuronium 0.6 mg/kg, or cisatracurium 0.15 mg/kg IV, which produced complete neuromuscular block. Upon return of the first response (T1) of TOF, a third of the initial dose was repeated. The duration of the initial dose and its variability were compared between agents. Duration of subsequent top‐up doses was assessed with mixed effect models. Spontaneous (from last return of T1) or neostigmine‐enhanced (from administration to complete recovery) recovery times were measured for each agent.

Results

Duration of action of the initial dose was [median (range)] 25 (10–60) min with rocuronium and 35 (15–45) min with cisatracurium (p = .231). The variability of rocuronium was 3.25 times larger than cisatracurium (p = .034). Duration of top‐up doses did not vary for either agent. Spontaneous recovery was shorter for rocuronium [15 (10–20) min] than cisatracurium [25 (15–45) min] (p = .02). Neostigmine‐enhanced recovery times were 5 (5–25) for rocuronium and 10 (5–10) for cisatracurium (p = .491).

Conclusions

Duration of action for a single dose is significantly more variable with rocuronium than cisatracurium. Time to spontaneous recovery was longer for cisatracurium, and cases of unexpectedly long recovery times were observed with both agents. Objective monitoring is recommended.
On the interdependence of ketone body oxidation, glycogen content, glycolysis and energy metabolism in the heart
Authors: Kadir Azrul Abdul , Stubbs Brianna J. , Chong Cher‐Rin , Lee Henry , Cole Mark , Carr Carolyn , Hauton David , McCullagh James , Evans Rhys D. , Clarke Kieran
Published: February 2023

In heart, glucose and glycolysis are important for anaplerosis and potentially therefore for d‐β‐hydroxybutyrate (βHB) oxidation. As a glucose store, glycogen may also furnish anaplerosis. We determined the effects of glycogen content on βHB oxidation and glycolytic rates, and their downstream effects on energetics, in the isolated rat heart. High glycogen (HG) and low glycogen (LG) containing hearts were perfused with 11 mM [5‐3H]glucose and/or 4 mM [14C]βHB to measure glycolytic rates or βHB oxidation, respectively, then freeze‐clamped for glycogen and metabolomic analyses. Free cytosolic [NAD+]/[NADH] and mitochondrial [Q+]/[QH2] ratios were estimated using the lactate dehydrogenase and succinate dehydrogenase reaction, respectively. Phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations were measured using 31P‐nuclear magnetic resonance spectroscopy. Rates of βHB oxidation in LG hearts were half that in HG hearts, with βHB oxidation directly proportional to glycogen content. βHB oxidation decreased glycolysis in all hearts. Glycogenolysis in glycogen‐replete hearts perfused with βHB alone was twice that of hearts perfused with βHB and glucose, which had significantly higher levels of the glycolytic intermediates fructose 1,6‐bisphosphate and 3‐phosphoglycerate, and higher free cytosolic [NAD+]/[NADH]. βHB oxidation increased the Krebs cycle intermediates citrate, 2‐oxoglutarate and succinate, the total NADP/H pool, reduced mitochondrial [Q+]/[QH2], and increased the calculated free energy of ATP hydrolysis (∆GATP). Although βHB oxidation inhibited glycolysis, glycolytic intermediates were not depleted, and cytosolic free NAD remained oxidised. βHB oxidation alone increased Krebs cycle intermediates, reduced mitochondrial Q and increased ∆GATP. We conclude that glycogen facilitates cardiac βHB oxidation by anaplerosis.

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Key points

Ketone bodies (d‐β‐hydroxybutyrate, acetoacetate) are increasingly recognised as important cardiac energetic substrates, in both healthy and diseased hearts.

As 2‐carbon equivalents they are cataplerotic, causing depletion of Krebs cycle intermediates; therefore their utilisation requires anaplerotic supplementation, and intra‐myocardial glycogen has been suggested as a potential anaplerotic source during ketone oxidation.

It is demonstrated here that cardiac glycogen does indeed provide anaplerotic substrate to facilitate β‐hydroxybutyrate oxidation in isolated perfused rat heart, and this contribution was quantified using a novel pulse–chase metabolic approach.

Further, using metabolomics and 31P‐MR, it was shown that glycolytic flux from myocardial glycogen increased the heart's ability to oxidise βHB, and βHB oxidation increased the mitochondrial redox potential, ultimately increasing the free energy of ATP hydrolysis.
Multiscale 3D genome reorganization during skeletal muscle stem cell lineage progression and aging
Authors: Zhao Yu , Ding Yingzhe , He Liangqiang , Zhou Qin , Chen Xiaona , Li Yuying , Alfonsi Maria Vittoria , Wu Zhenguo , Sun Hao , Wang Huating
Published: February 2023

Little is known about three-dimensional (3D) genome organization in skeletal muscle stem cells [also called satellite cells (SCs)]. Here, we comprehensively map the 3D genome topology reorganization during mouse SC lineage progression. Specifically, rewiring at the compartment level is most pronounced when SCs become activated. Marked loss in topologically associating domain (TAD) border insulation and chromatin looping also occurs during early activation process. Meanwhile, TADs can form TAD clusters and super-enhancer–containing TAD clusters orchestrate stage-specific gene expression. Furthermore, we uncover that transcription factor PAX7 is pivotal in enhancer-promoter (E-P) loop formation. We also identify cis-regulatory elements that are crucial for local chromatin organization at
Pax7
locus and
Pax7
expression. Lastly, we unveil that geriatric SC displays a prominent gain in long-range contacts and loss of TAD border insulation. Together, our results uncover that 3D chromatin extensively reorganizes at multiple architectural levels and underpins the transcriptome remodeling during SC lineage development and SC aging.
The evolution of universal cooperation
Authors: Gross Jörg , Méder Zsombor Z. , De Dreu Carsten K.W. , Romano Angelo , Molenmaker Welmer E. , Hoenig Laura C.
Published: February 2023

Humans work together in groups to tackle shared problems and contribute to local club goods that benefit other group members. Whereas benefits from club goods remain group bound, groups are often nested in overarching collectives that face shared problems like pandemics or climate change. Such challenges require individuals to cooperate across group boundaries, raising the question how cooperation can transcend beyond confined groups. Here, we show how frequent intergroup interactions allow groups to transition from group-bound to universal cooperation. With frequent intergroup interactions, reciprocity of cooperative acts permeates group boundaries and enables the evolution of universal cooperation. As soon as intergroup interactions take place frequently, people start to selectively reward cooperation aimed at benefitting everyone, irrespective of their group membership. Simulations further show that it becomes more difficult to overcome group-bound cooperation when populations are fragmented into many small groups. Our findings reveal important prerequisites for the evolution of universal cooperation.
Imaging of
Escherichia coli
K5 and glycosaminoglycan precursors via targeted metabolic labeling of capsular polysaccharides in bacteria
Authors: Wang Yu-Jia , Li Lian , Yu Jie , Hu Hong-Yu , Liu Zi-Xu , Jiang Wen-Jie , Xu Wei , Guo Xue-Ping , Wang Feng-Shan , Sheng Ju-Zheng
Published: February 2023

The introduction of unnatural chemical moieties into glycosaminoglycans (GAGs) has enormous potential to facilitate studies of the mechanism and application of these critical, widespread molecules. Unnatural
N
-acetylhexosamine analogs were metabolically incorporated into the capsule polysaccharides of
Escherichia coli
and
Bacillus subtilis
via bacterial metabolism. Targeted metabolic labeled hyaluronan and the precursors of heparin and chondroitin sulfate were obtained. The azido-labeled polysaccharides (purified or in capsules) were reacted with dyes, via bioorthogonal chemistry, to enable detection and imaging. Site-specific introduction of fluorophores directly onto cell surfaces affords another choice for observing and quantifying bacteria in vivo and in vitro. Furthermore, azido-polysaccharides retain similar biological properties to their natural analogs, and reliable and predictable introduction of functionalities, such as fluorophores, onto azido-
N
-hexosamines in the disaccharide repeat units provides chemical tools for imaging and metabolic analysis of GAGs in vivo and in vitro.
Interactive nanocluster compaction of the ELKS scaffold and Cacophony Ca
2+
channels drives sustained active zone potentiation
Authors: Ghelani Tina , Escher Marc , Thomas Ulrich , Esch Klara , Lützkendorf Janine , Depner Harald , Maglione Marta , Parutto Pierre , Gratz Scott , Matkovic-Rachid Tanja , Ryglewski Stefanie , Walter Alexander M. , Holcman David , O‘Connor Giles Kate , Heine Martin , Sigrist Stephan J.
Published: February 2023

At presynaptic active zones (AZs), conserved scaffold protein architectures control synaptic vesicle (SV) release by defining the nanoscale distribution and density of voltage-gated Ca
2+
channels (VGCCs). While AZs can potentiate SV release in the minutes range, we lack an understanding of how AZ scaffold components and VGCCs engage into potentiation. We here establish dynamic, intravital single-molecule imaging of endogenously tagged proteins at
Drosophila
AZs undergoing presynaptic homeostatic potentiation. During potentiation, the numbers of α1 VGCC subunit Cacophony (Cac) increased per AZ, while their mobility decreased and nanoscale distribution compacted. These dynamic Cac changes depended on the interaction between Cac channel’s intracellular carboxyl terminus and the membrane-close amino-terminal region of the ELKS-family protein Bruchpilot, whose distribution compacted drastically. The Cac-ELKS/Bruchpilot interaction was also needed for sustained AZ potentiation. Our single-molecule analysis illustrates how the AZ scaffold couples to VGCC nanoscale distribution and dynamics to establish a state of sustained potentiation.
Immunosuppressive reprogramming of neutrophils by lung mesenchymal cells promotes breast cancer metastasis
Authors: Gong Zheng , Li Qing , Shi Jiayuan , Li Peishan , Hua Li , Shultz Leonard D. , Ren Guangwen
Published: February 2023

Neutrophils, the most abundant innate immune cells, function as crucial regulators of the adaptive immune system in diverse pathological conditions, including metastatic cancer. However, it remains largely unknown whether their immunomodulatory functions are intrinsic or acquired within the pathological tissue environment. Here, using mouse models of metastatic breast cancer in the lungs, we show that, although neutrophils isolated from bone marrow (BM) or blood are minimally immunosuppressive, lung-infiltrating neutrophils are robustly suppressive of both T cells and natural killer (NK) cells. We found that this tissue-specific immunosuppressive capacity of neutrophils exists in the steady state and is reinforced by tumor-associated inflammation. Acquisition of potent immunosuppression activity by lung-infiltrating neutrophils was endowed by the lung-resident stroma, specifically CD140a
+
mesenchymal cells (MCs) and largely via prostaglandin-endoperoxide synthase 2 (PTGS2), the rate-limiting enzyme for prostaglandin E
2
(PGE
2
) biosynthesis. MC-specific deletion of
Ptgs2
or pharmacological inhibition of PGE
2
receptors reversed lung neutrophil–mediated immunosuppression and mitigated lung metastasis of breast cancer in vivo. These lung stroma–targeting strategies substantially improved the therapeutic efficacy of adoptive T cell–based immunotherapy in treating metastatic disease in mice. Collectively, our results reveal that the immunoregulatory effects of neutrophils are induced by tissue-resident stroma and that targeting tissue-specific stromal factors represents an effective approach to boost tissue-resident immunity against metastatic disease.
Impact of the family doctor system on the continuity of care for diabetics in urban China: a difference-in-difference analysis
Authors: Liu Xinyi , Zhang Luying , Chen Wen
Published: February 2023

Objectives

Our study aimed to examine whether the family doctor system can improve continuity of care for patients with diabetes.

Design

Registry-based, population-level longitudinal cohort study.

Setting

Linked data from the administrative Health Information System and the Health Insurance Claim Databases in a sample city in eastern China.

Participants

30 451 insured patients who were diagnosed with diabetes before January 2015 in the sample city, with ≥2 outpatient visits per year during 2014–2017. Diabetics in the intervention group had been registered with family doctor teams from 2015 to 2017, while those who had not registered were taken as the control group.

Interventions

The family doctor system was established in China mainly to strengthen primary care and rebuild referral systems. Residents were encouraged to register with family doctors to obtain continuous health management especially for chronic disease management.

Outcome measures

Continuity of care was measured by the Continuity of Care Index (COCI), Usual Provider Continuity Score (UPCS) and Sequential Continuity of Care Index (SECON) in 2014–2017.

Results

COCI, UPCS and SECON of all diabetics in this study increased between 2014 and 2017. A difference-in-difference approach was applied to measure the net effect of the family doctor system on continuity of care. Our model controlled for demographic and socioeconomic characteristics, and severity of disease at baseline. Compared with the control group, diabetics registered with family doctors obtained an average 0.019 increase in COCI (SE 0.002) (p<0.01), a 0.016 increase in UPCS (SE 0.002) (p<0.01) and a 0.018 increase in SECON (SE 0.002) (p<0.01).

Conclusion

This study provides evidence that the family doctor system can effectively improve continuity of care for patients with diabetes, which has substantial policy implications for further primary care reform in China.