bluuebunny/crossref_metadata_2025 huggingface dataset:
Structures of RecBCD in complex with phage-encoded inhibitor proteins reveal distinctive strategies for evasion of a bacterial immunity hub
Authors: Wilkinson M. , Wilkinson O.J. , Feyerherm C. , Fletcher E.E. , Wigley D.B. , Dillingham M.S.
Published: September 2022

Following infection of bacterial cells, bacteriophage modulate double-stranded DNA break repair pathways to protect themselves from host immunity systems and prioritise their own recombinases. Here we present biochemical and structural analysis of two phage proteins, gp5.9 and Abc2, which target the DNA break resection complex RecBCD. These exemplify two contrasting mechanisms for control of DNA break repair in which the RecBCD complex is either inhibited or co-opted for the benefit of the invading phage. Gp5.9 completely inhibits RecBCD by preventing it from binding to DNA. The RecBCD-gp5.9 structure shows that gp5.9 acts by substrate mimicry, binding predominantly to the RecB arm domain and competing sterically for the DNA binding site. Gp5.9 adopts a parallel coiled-coil architecture that is unprecedented for a natural DNA mimic protein. In contrast, binding of Abc2 does not substantially affect the biochemical activities of isolated RecBCD. The RecBCD-Abc2 structure shows that Abc2 binds to the Chi-recognition domains of the RecC subunit in a position that might enable it to mediate the loading of phage recombinases onto its single-stranded DNA products.
Subthreshold serotonin signals combined by the G proteins Gαq and Gαs activate the C. elegans egg-laying muscles
Authors: Olson Andrew C. , Butt Allison M. , Christie Nakeirah T.M. , Shelar Ashish , Koelle Michael R.
Published: September 2022

Individual neuron or muscle cells express many G protein coupled receptors (GPCRs) for neurotransmitters and neuropeptides. It remains unclear how these cells integrate multiple GPCR signals that all must act through the same few G proteins. We investigated how two serotonin GPCRs, Gαq-coupled SER-1 and Gαs-coupled SER-7, function together on the C. elegans egg-laying muscles to promote contraction and thus cause eggs to be laid. Using receptor null mutations and cell-specific knockdowns, we found that serotonin signaling through either SER-1/Gαq or SER-7/Gαs alone does not induce egg laying, but these subthreshold signals can combine to promote egg laying. However, using designer receptors or optogenetics to artificially induce high levels of either Gαq signaling or Gαs signaling in the muscles was sufficient to induce egg laying. Conversely, knocking down both Gαq and Gαs in the egg-laying muscle cells induced egg-laying defects stronger than those of a ser-7 ser-1 double knockout. These results suggest that, in the egg-laying muscles, multiple GPCRs for serotonin and other signals each produce weak effects that individually do not result in strong behavioral outcomes. However, they can combine to produce sufficient levels of Gαq and Gαs signaling to promote muscle activity and egg laying.
Unified establishment and epigenetic inheritance of DNA methylation through cooperative MET1 activity
Authors: Briffa Amy , Hollwey Elizabeth , Shahzad Zaigham , Moore Jonathan D. , Lyons David B. , Howard Martin , Zilberman Daniel
Published: September 2022

Methylation of CG dinucleotides (mCG), which regulates eukaryotic genome functions, is epigenetically propagated by Dnmt1/MET1 methyltransferases. How mCG is established and transmitted across generations despite imperfect enzyme fidelity remains mysterious. Here we show that MET1 de novo activity, which is enhanced by existing proximate methylation, seeds and stabilizes mCG in Arabidopsis thaliana genes. MET1 activity is restricted by active demethylation and suppressed by histone variant H2A.Z. Based on these observations, we develop a mathematical model that precisely recapitulates mCG inheritance dynamics and predicts intragenic mCG patterns and their population-scale variation given only CG site spacing as input. The model reveals that intragenic mCG undergoes large, millennia-long epigenetic fluctuations, and can therefore mediate evolution on this timescale. Our results demonstrate how genic methylation patterns are created, reconcile imperfect mCG maintenance with long-term stability, and establish a quantitative model that unifies the establishment and epigenetic inheritance of mCG.

Highlights

MET1 mediates a unified process of mCG establishment and maintenance within genes

ROS1 and H2A.Z regulate the epigenetic dynamics of genic mCG

A mathematical model predicts genic mCG patterns and their population variance

Genic mCG undergoes large epigenetic fluctuations that can last thousands of years
Differential role of dopamine D3 receptor through balanced modulation of Akt/mTOR and ERK1/2 activity in the reactivation of cocaine rewarding memories evoked by psychological versus physiological stress
Authors: Franco-García Aurelio , Guerrero-Bautista Rocío , Hidalgo Juana María , Milanés María Victoria , Gómez-Murcia Victoria , Núñez Cristina
Published: September 2022

Stress is an important trigger of relapses in cocaine use. These relapses engage the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the dentate gyrus (DG). Further, preclinical research signals D3 receptor (D3R) antagonists as promising therapeutic tools to attenuate cocaine reward and relapse. Therefore, we assessed the effect of SB-277011-A, a D3R antagonist, in the activity of Akt/mTOR and MEK/ERK1/2 pathways in these areas during the reinstatement of cocaine-induced conditioned place preference (CPP) evoked by psychological (restraint) and physiological (tail pinch) stress. Both stimuli reactivated the extinguished cocaine-CPP, but only restrained animals decreased their locomotor activity during reinstatement. Moreover, p-Akt, p-mTOR and p-ERK1/2 activity in the BLA and DG of restrained animals decreased during the reactivation of cocaine memories, contrasting to tail-pinched mice. While D3R blockade prevented stress-induced CPP reactivation and plasmatic corticosterone enhancement, SB-277011-A distinctly modulated Akt, mTOR and ERK1/2 activities in the BLA and DG based on the stressor and the dose of antagonist. Corticosterone may be partially responsible for these variations as we found high correlations among its levels and mTOR and/or Akt activity in the BLA and DG of restrained animals receiving SB-277011-A. Besides, locomotor activity of animals receiving 48 mg/kg of the antagonist highly correlated with p-mTOR/mTOR and p-ERK1/2 /ERK1/2 in the BLA during restraint- and tail pinch-induced relapse in cocaine-CPP, respectively. Hence, our study endorses D3R antagonists as therapeutic tools to prevent stress-induced relapses in drug use through a complex balance of Akt/mTOR and MEK/ERK1/2 pathways in memory-processing brain nuclei.
Stimulation-responsive enhancers regulate inflammatory gene activation through retention and modification of H2A.Z-variant accessible nucleosomes
Authors: Sporrij Audrey , Prasad Meera , Muhire Brejnev , Fast Eva M. , Manning Margot E. , Choudhuri Avik , Weiss Jodi D. , Koh Michelle , Yang Song , Kingston Robert E. , Tolstorukov Michael Y. , Clevers Hans , Zon Leonard I.
Published: September 2022

Prostaglandin E2 (PGE2) and 16,16-dimethyl-PGE2 (dmPGE2) are important regulators of hematopoietic stem and progenitor cell (HSPC) fate and offer potential to enhance stem cell therapies1,2. The mechanism of gene regulation in response to dmPGE2 is poorly understood. Here, we show that dmPGE2 regulates inflammatory gene induction by modulating the chromatin architecture and activity of enhancer elements in human HSPCs. We identified the specific genomic reorganization at stimuli-responsive enhancers that permits rapid transcriptional activation. We found that dmPGE2-inducible enhancers retain MNase-accessible, H2A.Z-variant nucleosomes that are permissive to binding of the transcription factor CREB. CREB binding to enhancer nucleosomes is concomitant with deposition of the histone acetyltransferases p300 and Tip60 on chromatin. Subsequent H2A.Z acetylation improves chromatin accessibility at stimuli-responsive enhancers. Our findings support a model where histone variant nucleosomes retained within inducible enhancers facilitate transcription factor (TF) binding. Acetylation of histone variant nucleosomes by TF-associated nucleosome remodelers creates the accessible nucleosome landscape required for immediate enhancer activation and gene induction. Our work provides a mechanism by which inflammatory mediators such as dmPGE2 lead to acute transcriptional changes and alter HSPC behavior.
Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant
Authors: Scheaffer Suzanne M. , Lee Diana , Whitener Bradley , Ying Baoling , Wu Kai , Jani Hardik , Martin Philippa , Amato Nicholas J. , Avena Laura E. , Berrueta Daniela Montes , Schmidt Stephen D. , O’Dell Sijy , Nasir Arshan , Chuang Gwo-Yu , Stewart-Jones Guillaume , Koup Richard A. , Doria-Rose Nicole A. , Carfi Andrea , Elbashir Sayda M. , Thackray Larissa B. , Edwards Darin K. , Diamond Michael S.
Published: September 2022

The emergence of SARS-CoV-2 variants in the Omicron lineage with large numbers of substitutions in the spike protein that can evade antibody neutralization has resulted in diminished vaccine efficacy and persistent transmission. One strategy to broaden vaccine-induced immunity is to administer bivalent vaccines that encode for spike proteins from both historical and newly-emerged variant strains. Here, we evaluated the immunogenicity and protective efficacy of two bivalent vaccines that recently were authorized for use in Europe and the United States and contain two mRNAs encoding Wuhan-1 and either BA.1 (mRNA-1273.214) or BA.4/5 (mRNA-1273.222) spike proteins. As a primary immunization series in BALB/c mice, both bivalent vaccines induced broader neutralizing antibody responses than the constituent monovalent vaccines (mRNA-1273 [Wuhan-1], mRNA-1273.529 [BA.1], and mRNA-1273-045 [BA.4/5]). When administered to K18-hACE2 transgenic mice as a booster at 7 months after the primary vaccination series with mRNA-1273, the bivalent vaccines induced greater breadth and magnitude of neutralizing antibodies compared to an mRNA-1273 booster. Moreover, the response in bivalent vaccine-boosted mice was associated with increased protection against BA.5 infection and inflammation in the lung. Thus, boosting with bivalent Omicron-based mRNA-1273.214 or mRNA-1273.222 vaccines enhances immunogenicity and protection against currently circulating SARS-CoV-2 strains.
The dynamic response of quorum-sensing to density is robust to signal supplementation and signal synthase knockouts
Authors: Rattray Jennifer B. , Kramer Patrick , Gurney James , Thomas Stephen , Brown Sam P.
Published: September 2022

Quorum sensing (QS) is a widespread mechanism of environment sensing and behavioral coordination in bacteria. At its core, QS is based on the production, sensing and response to small signaling molecules. Previous work with Pseudomonas aeruginosa shows that QS can be used to achieve quantitative resolution and deliver a dosed response to the bacteria’s density environment, implying a sophisticated mechanism of control. To shed light on how the mechanistic signal components contribute to graded responses to density, we assess the impact of genetic (AHL signal synthase deletion) and/or signal supplementation (exogenous AHL and PQS addition) perturbations on lasB reaction-norms to changes in density. Our approach condenses data from 2,000 timeseries (over 74,000 individual observations) into a comprehensive view of QS-controlled gene expression across variation in genetic, environmental, and signal determinants of lasB expression. We first confirm that deleting either (ΔlasI, ΔrhlI) or both (ΔlasIrhlI) signal synthase genes attenuates QS response. In the ΔrhlI background we show persistent yet attenuated density-dependent lasB expression due to native 3-oxo-C12 signaling. We then test if density-independent quantities of signal (3-oxo-C12, C4, PQS or combined) added to the WT either flatten or increase the reaction norm and find that the WT response is robust to all tested concentrations of signal, alone or in combination. We then move to progressively supplementing the genetic knockouts and find that cognate signal supplementation (ΔlasI+3-oxo-C12, ΔrhlI+C4) is sufficient to restore lasB expression and as well as reactivity to density encoded by the intact signal synthase. We also find that dual supplementation of the double synthase knockout restores expression but does not flatten the reaction norm. Despite adding a density-independent amount of AHL, the double signal synthase can still quantitively sense density. Our results show that a positive reaction norm to density is robust to multiple combinations of gene deletion and density-independent signal supplementation and that while density-independent signal supplementation can increase mean expression, the WT QS still retains the ability to quantitatively respond to density. Our work develops a modular approach to query the robustness and mechanistic bases of the central environmental sensing phenotype of quorum sensing.
DrosophilaMales Use 5′-to-3′ Phased Biogenesis to MakeStellate-silencing piRNAs that Lack Homology to Maternally Deposited piRNA Guides
Authors: Venkei Zsolt G. , Gainetdinov Ildar , Starostik Margaret R. , Choi Charlotte P. , Chen Peiwei , Balsara Chiraag , Whitfield Troy W. , Bell George W. , Feng Suhua , Jacobsen Steven E. , Aravin Alexei A. , Kim John K. , Zamore Philip D. , Yamashita Yukiko M.
Published: September 2022

PIWI-interacting RNAs (piRNAs) direct PIWI proteins to silence complementary targets such as transposons. In animals with a maternally specified germline, e.g.Drosophila melanogaster, maternally deposited piRNAs initiate piRNA biogenesis in the progeny. Normal fertility inD. melanogastermales requires repression of tandemly repeatedStellategenes by piRNAs fromSuppressor of Stellate[Su(Ste)]. Because theSu(Ste)loci are on the Y chromosome,Su(Ste)piRNAs are not deposited in oocytes. How the male germline producesSu(Ste)piRNAs in the absence of maternally depositedSu(Ste)piRNAs is unknown. Here, we show thatSu(Ste)piRNAs are made in the early male germline via 5′-to-3′ phased piRNA biogenesis triggered by maternally deposited1360/Hoppeltransposon piRNAs. Strikingly, deposition ofSu(Ste)piRNAs from XXY mothers obviates the need for phased piRNA biogenesis in sons. Together, our study uncovers the developmentally programmed mechanism that allows fly mothers to protect their sons using a Y-linked piRNA locus.
Comparing the representation of a simple visual stimulus across the cerebellar network
Authors: Prat Ot , Petrucco Luigi , Štih Vilim , Portugues Ruben
Published: September 2022

The cerebellum is a highly conserved structure of the vertebrate central nervous system that plays a role in the timing and calibration of motor sequences. Its function is supported by the convergence of fibers from granule cells (GCs) and inferior olive neurons (IONs) onto Purkinje cells (PCs). Theories of cerebellar function postulate that IONs convey error signals to PCs that, paired with the contextual information provided by GCs, can be used as a teaching signal to guide motor learning.

Here, we use the larval zebrafish to investigate (i) how sensory representations of the same stimulus vary across GCs and IONs and (ii) how PC activity reflects these two different input streams. We use population calcium imaging to measure the cell responses to flashes of diverse luminance and duration to show that IONs and GCs encode different stimulus properties. First, most GCs show tonic and graded responses, as opposed to IONs, whose activity peaks only at on and off luminance transitions, in agreement with the notion that GCs and IONs encode context and error information, respectively. Secondly, we show that GC activity is patterned over time: some neurons had sustained responses for the entire duration of the stimulus, while in others activity was ramping up with slow time constants. This suggests that, by performing temporal integration, GCs could provide a basis that PCs may use to decode time. Finally, we show how PC activity can be largely reconstructed by a linear combination of granule cells and inferior olive neurons. Together, our observations give support to the notion of an error signal coming from IONs, and provide the first experimental evidence for a temporal patterning of GC activity over many seconds.
Comparative multi-OMICS single cell atlas of five COVID-19 (rAdVV and mRNA) vaccines describe unique and distinct mechanisms of action
Authors: Singh Yogesh , Selting Antje Schulze , Gabernet Gisela , Ray Urvi , Bajaj Rimpi , Ali Mohammed , Loitz Marion , Hammer Vincent , Buena-Atienza Elena , Ruschil Christoph , Huebener-Schmid Jeannette , Kowarik Markus , Salker Madhuri S , Casadei Nicolas , Nahnsen Sven , Kremsner Peter , Ossowski Stephan , Altmann Daniel M ,   Deutsche COVID-19 OMICS Initiative (DeCOI), Riess Olaf
Published: September 2022

COVID-19 vaccines based on a range of expression platforms have shown considerable protective efficacy, generating antibody and T cell immune responses. However, molecular pathways underpinning COVID-19 vaccine priming of immunity against the SARS-CoV-2 virus have not yet been explored extensively. This analysis is critical to optimization of future vaccination strategies, schedules, and combinations. Thus, we investigated a cohort of individuals pre- and post-vaccination to understand the humoral and cellular immune response against different COVID-19 vaccines, including recombinant adenoviral vector (rAdVV) and mRNA-based vaccines. Single-cell RNA sequencing allowed characterization of monocytes, T, NK and B cell activation at the transcriptomics/proteomic level, in response to different COVID-19 vaccines. Our data revealed that different COVID-19 vaccines elicit a unique and distinct mechanism of action. Specifically, we revealed that rAdVV vaccines negatively regulate CD4+T cell activation, leukocytes chemotaxis, IL-18 signalling and antigen presentation by monocytes whilst mRNA vaccines positively regulate NKT cell activation, platelets activation and chemokine signalling pathways. An antigen-specific T cell response was already observed following the 1stvaccine dose and was not further augmented after the subsequent 2nddose of the same vaccine and it was dependent on the type of vaccination used. Our integrated three layered-analyses highlights that COVID-19 vaccines evoke a strong but divergent immune response at the RNA, protein, and cellular levels. Our approach is able to pinpoint efficacy and mechanisms controlling immunity to vaccination and open the door for better vaccination which could induce innate and adaptive immunity equally in the long term.

Key findings

Decrease in major three cell types classical and non-classical monocytes and NK type III cells after COVID-19 vaccination

Individual vaccination (AZ, JJ, MD, PB) has differential effect on various immune cell subsets and regulates unique cell populations, whilst no change was observed for CV vaccination

rAdVV and mRNA vaccines have different mechanism of action for activation of lymphocytes and monocytes, respectively

rAdVV vaccines negatively regulates CD4+T cell activation, leukocytes chemotaxis, IL-18 signalling and antigen presentation whilst mRNA vaccines positively regulate NKT cell activation, platelets activation and chemokine signalling pathways.

An antigen-specific T cell response was prompted after the 1stvaccine dose and not augmented after the subsequent 2nddose of the same vaccine.

Graphical abstract
Emergency remote learning (ERL) in the COVID-19 era: perceived experience of Indian learners of higher education
Authors: Mukherjee Mrinal , Maity Chanchal
Published: September 2022

Purpose

The COVID-19 pandemic compelled the education system to switch over to emergency learning-teaching that is organised remotely. The present study investigated the experience of emergency remote learning (ERL) provided to higher-education learners. The study explores learners' perceived experience regarding the quality of learning resources, the effectiveness of teaching in a virtual climate and the scope of interaction in ERL.

Design/methodology/approach

Utilising a snowball sampling method, data were obtained from 470 Indian students of higher education through a cross-sectional online survey using a questionnaire through social media platforms. Data were analysed with relevant statistics.

Findings

The majority of students agreed that they had benefited from ERL. The overall impression of the ERL is positive; nevertheless, the students are perplexed and lack confidence in many aspects of the ERL. The Quality of ERL Resources, Teaching Effectiveness, Peer Interaction and Workloads were found to be significant factors in determining the quality of ERL.

Originality/value

Learning from the crisis of a pandemic is paramount for the education system. The education system could not go back to what was considered normal before the pandemic; rather it is time to assess and finalise strategies from the experience during this pandemic that could be taken by the higher-education institutions to make the ecosystem better equipped to create 21st-century learning climate. Accommodating the components of remote learning-teaching and engaging technology towards hybridisation are the needs of the time. Hence, assessing the quality of ERL from the learner's perspective might contribute to redesigning future remote learning.
Sources of negative memorable experiences: Finnish Airbnb guest perspectives
Authors: Sthapit Erose , Björk Peter
Published: September 2022

Purpose

This study aims to bridge the gaps in the extant literature on memorable tourism experiences (MTEs) and Airbnb by exploring the sources of negative memorable Airbnb experiences among Finnish guests.

Design/methodology/approach

This study used a qualitative approach and used data collected through semi-structured interviews. The sampling criteria for selecting participants were that they must be Finnish nationals who had booked and stayed in an Airbnb accommodation within the past 36 months. The participants were selected using a criteria-based snowball sampling technique. A qualitative empirical study was conducted using self-structured interviews that were completed by 18 Finnish tourists who had stayed at an Airbnb property in the past three years.

Findings

Three main sources constitute the conceptual framework of a negative memorable Airbnb experience: unclean accommodations, unpleasant host behaviour and poor customer service.

Practical implications

Airbnb management should make efforts to reduce guests’ negative experiences. This goal can be achieved by developing service-quality-management policies and strategies that are standardised, clear and universally applicable to all hosts. In addition, Airbnb management should recruit qualified customer service personnel and equip them with service recovery skills through training and control mechanisms. Such training should focus on upgrading their ability to handle complaints.

Originality/value

This study responds to the need to examine negative incidents that are a part of MTEs and the sources of negative memories. The originality of this study includes the extension of the existing literature on MTEs and Airbnb, as a conceptual framework of negative memorable Airbnb experiences that comprises three main components: unclean rooms, unpleasant host behaviour and poor customer service has been proposed.
Experience-based systematic construction hazard warning
Authors: Wang Mohan , Liao Pin-Chao
Published: September 2022

Purpose

Hazard warning schemes provide efficient hazard recognition and promote project safety. Nevertheless, these schemes perform poorly because the warning information is calibrated for individual characters and is not prioritized for the entire system. This study proposes a hazard warning scheme that prioritizes hazard characters from the inspection process based on the inspectors' experience.

Design/methodology/approach

First, hazard descriptions were decomposed into their characters, forming a double-layer network. Second, warning schemes based on cascading effects were proposed. Third, character-based warning schemes were simulated for various experiences.

Findings

The results show that when a specific hazard is detected, the degree centrality is the most effective parameter for prioritization, and hazard characters should be prioritized based on betweenness centrality for experienced inspectors, whereas degree centrality is preferred for novice inspectors.

Originality/value

The warning scheme theoretically supplements the information-processing theory in construction hazard warnings and provides a practical warning scheme with priority for the development of automated hazard navigation systems.
Public–private partnerships: a collaborative framework for ensuring project sustainable operations
Authors: Liu Bingsheng , Li Juankun , Wang Dan , Liu Henry , Wu Guangdong , Yuan Jingfeng
Published: September 2022

Purpose

This study aims to develop a collaborative governance framework (CGF) to systematically investigate the impeding factors (IFs) in terms of the operational sustainability of PPPs. It examines the transmission pattern (i.e. the way in which network members react to each other) of the IFs network.

Design/methodology/approach

Literature review and interview were adopted to identify the IFs. Then, with the data collected from the interview in China, the social network analysis and interpretive structure model were synergised to examine the chain reaction, driving and dependent powers, and hierarchical structure of the identified IFs.

Findings

The results reveal that the cognition, institutional, financial and participation aspects are key barriers confronted by PPP sustainability, and the government plays a leading role in controlling factors causing sustainability-related problems in PPPs. Weak government leadership and institutional environment were identified as the most fundamental reasons triggering a chain of IFs, while project governance and management activities act as bridge nodes that play an intermediary role in the IFs network.

Research limitations/implications

This research contributes to the literature on PPP governance by (1) bridging the literature gap through the development of CGF for explaining the governance of PPP sustainability with a holistic view that considers both macro environment and operational project processes; and (2) identifying the transmission pattern of IFs network which uncovers the underlying dynamics causing the unsustainable operation of PPPs.

Practical implications

This research provides practitioners with a list of key checkpoints for preventing failure escalation, enables decision-makers to prioritise obstacle-mitigation efforts and develop a feasible process to control PPP operation, and offers management countermeasures to remove the key barriers impeding PPP sustainability.

Originality/value

This study is novel for adopting network-oriented techniques to quantify the relative importance of the IFs and examine the transmission pattern of the IFs system. Therefore, it visualises the complex underlying dynamics causing unsustainable PPP operation, identifies root and direct causes of PPP failures, and provides decision-makers with insights into sustaining PPP sustainability from a network-oriented perspective.
Project managers' reactions to project disruption: sponsor actions versus environmental uncertainty
Authors: Franke Henrik , Wynstra Finn , Nullmeier Fabian , Nullmeier Chloe
Published: September 2022

Purpose

Managing projects is an important part of operations management, but many projects fail. This study focuses on attribution processes of such disruption from the underrepresented perspective of the project manager. The authors consider two types of causes: the more frequently researched environmental uncertainty (i.e. uncontrollable events) and the scarcely researched uncertainty imposed by non-collaborative project sponsors (i.e. other-controllable events).

Design/methodology/approach

The authors test conceptual arguments grounded in attribution theory and the notion of psychological contracts in a scenario-based experiment among 325 practicing project managers.

Findings

The findings indicate that non-collaborative project sponsors negatively affect project managers' motivation, whereas uncontrollable disruptions leave hope to achieve positive future outcomes. This latter effect is further strengthened when project managers have an internal attribution style. They tend to blame the disruption on themselves and generally feel in control of achieving success even if they are not.

Originality/value

These socio-psychological insights nuance the economic idea that uncertainty reduces motivation per se in the context of project disruption appraisal. The authors contribute to the behavioral project management literature and general attribution theory and help guide the allocation of resources during the recovery of failed projects.
Output measurement in professional public organizations: insights from European justice systems
Authors: Pekkanen Petra , Pirttilä Timo
Published: September 2022

Purpose

The aim of this study is to empirically explore and analyze the concrete tasks of output measurement and the inherent challenges related to these tasks in a traditional and autonomous professional public work setting – the judicial system.

Design/methodology/approach

The analysis of the tasks is based on a categorization of general performance measurement motives (control-motivate-learn) and main stakeholder levels (society-organization-professionals). The analysis is exploratory and conducted as an empirical content analysis on materials and reports produced in two performance improvement projects conducted in European justice organizations.

Findings

The identified main tasks in the different categories are related to managing resources, controlling performance deviations, and encouraging improvement and development of performance. Based on the results, key improvement areas connected to output measurement in professional public organizations are connected to the improvement of objectivity and fairness in budgeting and work allocation practices, improvement of output measures' versatility and informativeness to highlight motivational and learning purposes, improvement of professional self-management in setting output targets and producing outputs, as well as improvement of organizational learning from the output measurement.

Practical implications

The paper presents empirically founded practical examples of challenges and improvement opportunities related to the tasks of output measurement in professional public organization.

Originality/value

This paper fulfils an identified need to study how general performance management motives realize as concrete tasks of output measurement in justice organizations.
The perceived impact of physician shortages on human resource strategies in German hospitals – a resource dependency perspective
Authors: Schnack Helge , Uthoff Sarah Anna Katharina , Ansmann Lena
Published: September 2022

Purpose

Like other European countries, Germany is facing regional physician shortages, which have several consequences on patient care. This study analyzes how hospitals perceive physician shortages and which strategies they adopt to address them. As a theoretical framework, the resource dependency theory is chosen.

Design/methodology/approach

The authors conducted 20 semi-structured expert interviews with human resource officers, human resource directors, and executive directors from hospitals in the northwest of Germany. Hospitals of different ownership types, of varying sizes and from rural and urban locations were included in the sample. The interviews were analyzed by using qualitative content analysis.

Findings

The interviewees reported that human resource departments in hospitals expand their recruiting activities and no longer rely on one single recruiting instrument. In addition, they try to adapt their retaining measures to physicians' needs and offer a broad range of employment benefits (e.g. childcare) to increase attractiveness. The study also reveals that interviewees from small and rural hospitals report more difficulties with attracting new staff and therefore focus on recruiting physicians from abroad.

Practical implications

Since the staffing situation in German hospitals will not change in the short term, the study provides suggestions for hospital managers and health policy decision-makers in dealing with physician shortages.

Originality/value

This study uses the resource dependency theory to explain hospitals' strategies for dealing with healthcare staff shortages for the first time.
Analyzing the law qualitatively
Authors: Mitchell Matthew
Published: September 2022

Purpose

This article develops a methodological framework to support qualitative analyses of legal texts. Scholars across the social sciences and humanities use qualitative methods to study legal phenomena but often overlook formal legal texts as productive sites for analysis. Moreover, when qualitative researchers do analyze legal texts, they rarely discuss the methodological underpinnings that support their approach. A thorough consideration of the methodological underpinnings of qualitative approaches to legal analysis is therefore warranted.

Design/methodology/approach

By bringing critical legal theory into conversation with qualitative methodology, this article outlines a set of key principles to inform qualitative approaches to reading the law.

Findings

To construct this methodological framework, this article first distinguishes between qualitative approaches to textual analysis and the doctrinal approaches undertaken in legal practice and formal legal scholarship. It then considers how this qualitative approach might be applied to one particular genre of legal text: namely, judicial opinions, otherwise known as reasons for judgment. In doing so, it argues that robust qualitative analyses of legal texts must consider the unique characteristics of those texts, such as their distinct form, voice, rhetorical structure, and performative capabilities.

Originality/value

The methodological framework outlined here should encourage qualitative researchers to approach legal texts more readily and challenge the hegemony of doctrinal approaches to legal interpretation in social science research.
Triggering a patient-driven service innovation to foster the service ecosystem well-being: a case study
Authors: Megaro Antonietta , Carrubbo Luca , Polese Francesco , Sirianni Carlo Alessandro
Published: September 2022

Purpose

The aim of this paper is to understand if service innovation (Helkkula et al., 2018), based on artificial intelligence (AI) systems, may guarantee healthcare service ecosystem (H-SES) well-being (Frow et al., 2019; Beirão et al., 2017), taking into account that many doubts relieved in terms of transparency may compromise the patients' perceived quality of health services provided through AI systems.

Design/methodology/approach

A literature review on service innovation, detected in terms of value co-creation, and service ecosystem, investigated in terms of well-being, is drawn. To analyze the implications of service innovation on a H-SES well-being, through the technology acceptance degree and predisposition to use by actors, a case study based on TAM-model 3 determinants as categories is carried out.

Findings

AI-based service innovation archetypes in healthcare may be considered as antecedents of the service ecosystem well-being conditions as long as they enable actors to co-create value. To make it possible, a patient-driven service innovation is necessary in order to mitigate the risks of its inactivity due to fears in terms of transparency.

Originality/value

Service innovation and service ecosystem well-being may be studied in an integrated way, with a multidisciplinary approach, and are linked by value co-creation, because only thanks a patient-driven service innovation is possible to foster service ecosystem well-being in healthcare.
Volatile fingerprints of different parts of Chongming saffron (Crocus sativus) flowers by headspace‐gas chromatography‐ion mobility spectrometry and in vitro bioactive properties of the saffron tepals
Authors: Yao Lingyun , Guo Shuangfei , Wang Huatian , Feng Tao , Sun Min , Song Shiqing , Hou Feina
Published: September 2022

In this work, the volatile fingerprints of different parts of Chongming saffron flowers (stigmas, stamens, and tepals) were analyzed and compared for the first time by headspace‐gas chromatography‐ion mobility spectrometry. Three different parts of saffron flowers could be clearly distinguished using principal component analysis based on signal intensity data of gas chromatography‐ion mobility spectrometry. Therefore, gas chromatography‐ion mobility spectrometry coupled with principal component analysis method could be employed as a new method for authentication and quality control of saffron for the reason of frequent addition with stamens and/or tepals as adulterants in saffron. Moreover, the bioactive composition (total flavonoids, total phenolics, and total anthocyanins) and bioactive properties of saffron tepals were evaluated. The results indicated that aqueous, ethanol, and ethyl acetate extracts of saffron tepals exhibited good radical scavenging (2,2‐Diphenyl‐1‐picrylhydrazyl, ABTS, and OH) and enzyme (α‐amylase/α‐glucosidase) inhibition activities, which probably were attributed to the bioactive components contained in the extracts. This approach would provide the important information for monitoring the quality of saffron as well as exploring the utilization of saffron tepals in functional food technology.

Practical Application

This study demonstrated that the HS‐GC‐IMS method might be used as a new strategy for quality control of saffron, and the saffron tepals were rich source of bioactive components that could be used in health‐promoting products.
Biocontrol: Endophytic bacteria could be crucial to fight soft rot disease in the rare medicinal herb, Anoectochilus roxburghii
Authors: Xing Bingcong , Zheng Ying , Zhang Man , Liu Xinting , Li Lihong , Mou Chenhao , Wu Qichao , Guo Haipeng , Shao Qingsong
Published: September 2022

Microbial destabilization induced by pathogen infection has severely affected plant quality and output, such as Anoectochilus roxburghii, an economically important herb. Soft rot is the main disease that occurs during A. roxburghii culturing. However, the key members of pathogens and their interplay with non‐detrimental microorganisms in diseased plants remain largely unsolved. Here, by utilizing a molecular ecological network approach, the interactions within bacterial communities in endophytic compartments and the surrounding soils during soft rot infection were investigated. Significant differences in bacterial diversity and community composition between healthy and diseased plants were observed, indicating that the endophytic communities were strongly influenced by pathogen invasion. Endophytic stem communities of the diseased plants were primarily derived from roots and the root endophytes were largely derived from rhizosphere soils, which depicts a possible pathogen migration image from soils to roots and finally the stems. Furthermore, interactions among microbial members indicated that pathogen invasion might be aided by positively correlated native microbial members, such as Enterobacter and Microbacterium, who may assist in colonization and multiplication through a mutualistic relationship in roots during the pathogen infection process. Our findings will help open new avenues for developing more accurate strategies for biological control of A. roxburghii bacterial soft rot disease.
Salinomycin biosynthesis reversely regulates the β‐oxidation pathway in Streptomyces albus by carrying a 3‐hydroxyacyl‐CoA dehydrogenase gene in its biosynthetic gene cluster
Authors: Wei Jiaxiu , Chen Binbin , Dong Jianxin , Wang Xueyu , Li Yongquan , Liu Yingchun , Guan Wenjun
Published: September 2022

Streptomyces is well known for synthesis of many biologically active secondary metabolites, such as polyketides and non‐ribosomal peptides. Understanding the coupling mechanisms of primary and secondary metabolism can help develop strategies to improve secondary metabolite production in Streptomyces. In this work, Streptomyces albus ZD11, an oil‐preferring industrial Streptomyces strain, was proved to have a remarkable capability to generate abundant acyl‐CoA precursors for salinomycin biosynthesis with the aid of its enhanced β‐oxidation pathway. It was found that the salinomycin biosynthetic gene cluster contains a predicted 3‐hydroxyacyl‐CoA dehydrogenase (FadB3), which is the third enzyme of β‐oxidation cycle. Deletion of fadB3 significantly reduced the production of salinomycin. A variety of experimental evidences showed that FadB3 was mainly involved in the β‐oxidation pathway rather than ethylmalonyl‐CoA biosynthesis and played a very important role in regulating the rate of β‐oxidation in S. albus ZD11. Our findings elucidate an interesting coupling mechanism by which a PKS biosynthetic gene cluster could regulate the β‐oxidation pathway by carrying β‐oxidation genes, enabling Streptomyces to efficiently synthesize target polyketides and economically utilize environmental nutrients.
Myeloid cell‐specific mutation of Spi1 selectively reduces M2‐biased macrophage numbers in skeletal muscle, reduces age‐related muscle fibrosis and prevents sarcopenia
Authors: Wang Ying , Welc Steven S. , Wehling‐Henricks Michelle , Kong Ying , Thomas Connor , Montecino‐Rodriguez Enca , Dorshkind Kenneth , Tidball James G.
Published: September 2022

Intramuscular macrophages play key regulatory roles in determining the response of skeletal muscle to injury and disease. Recent investigations showed that the numbers and phenotype of intramuscular macrophages change during aging, suggesting that those changes could influence the aging process. We tested that hypothesis by generating a mouse model that harbors a myeloid cell‐specific mutation of Spi1, which is a transcription factor that is essential for myeloid cell development. The mutation reduced the numbers of macrophages biased to the CD163+/CD206+ M2 phenotype in muscles of aging mice without affecting the numbers of CD68‐expressing macrophages and reduced the expression of transcripts associated with the M2‐biased phenotype. The mutation did not affect the colony‐forming ability or the frequency of specific subpopulations of bone marrow hematopoietic cells and did not affect myeloid/lymphoid cell ratios in peripheral blood leukocyte populations. Cellularity of most myeloid lineage cells was not influenced by the mutation. The Spi1 mutation in bone marrow‐derived macrophages in vitro also did not affect expression of transcripts that indicate the M2‐biased phenotype. Thus, myeloid cell‐targeted mutation of Spi1 influences macrophage phenotype in muscle but did not affect earlier stages of differentiation of cells in the macrophage lineage. The mutation reduced age‐related muscle fibrosis, which is consistent with the reduction of M2‐biased macrophages, and reduced expression of the pro‐fibrotic enzyme arginase. Most importantly, the mutation prevented sarcopenia. Together, our observations indicate that intramuscular, M2‐biased macrophages play significant roles in promoting detrimental, age‐related changes in muscle.
A qualitative analysis of adding kindness into the ISBAR handover tool
Authors: de Senneville Lizzie Liew , Brewin Andrew , Thomas Alarna , Calvert Katrina
Published: September 2022

Background

The COVID pandemic has highlighted the stresses experienced by our medical workforce, with worldwide publications attesting to high rates of depression, anxiety and burnout, particularly in junior doctors. Many studies focus on reporting on the prevalence of mental health issues, but not many report on interventional strategies. One of the most stressful interactions in the day of a junior doctor is the medical handover. The incorporation of kindness into clinical handover has coined the term ‘KISBAR’ to underline the importance of delivering handover in a kind manner.

Aim

The aim is to analyse the efficacy of a novel intervention by introducing an emotional support representative to participate in the morning labour ward handover.

Methods

We undertook an ethnographic constructivist qualitative research project in a tertiary hospital in Perth, Western Australia, using focus groups to explore the views of junior medical staff on the KISBAR handover tool in the specific context of labour ward handover. Fifty per cent of the total junior doctors from the hospital participated in this study.

Results

Four dominant themes arose from analysis of the focus group discussions: (i) inherent stress experienced by junior doctors during the labour ward handover process, (ii) support strategies for junior doctors during labour ward handover; (iii) role modelling and the hidden curriculum aspects of communication from senior doctors at labour ward handover; and (iv) benefit of having an emotional support person present for labour ward handover.

Conclusion

Our study confirmed the benefit of having an emotional support person present at labour ward handover: improved perception of safety and an environment that junior doctors found to be supportive. This is a novel and reproducible interventional strategy which is applicable to various obstetric units around Australia.
Ferroptosis is involved in corpus cavernosum smooth muscle cells impairment in diabetes mellitus‐induced erectile dysfunction
Authors: Xu Wenchao , Sun Taotao , Wang Jiaxin , Wang Tao , Wang Shaogang , Liu Jihong , Liu Kang , Li Hao
Published: September 2022

Backgrounds

Erectile dysfunction (ED) is a common andrological disorder that tends to afflict diabetic patients, among others. Pharmacological therapy of diabetes mellitus‐induced ED (DMED) is ineffective, as it is linked with smooth muscle cell loss in the corpus cavernosum. Ferroptosis is a recently identified kind of cell death evoked by lipid peroxidation, and it is connected with a number of diabetic complications.

Objectives

To investigate the role of ferroptosis in DMED.

Materials and methods

We established the rat model of DMED and conducted a combined analysis of RNA sequencing (RNA‐seq) and Gene Expression Omnibus (GEO) data to identify differentially expressed genes (DEGs). Next, DMED disease targets were determined by cross‐referencing DEGs and DMED‐related genes in the DisGeNET, GenCLiP3, and GeneCards databases. Additionally, these targets were analyzed using “clusterProfiler” in R utilizing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations. Immunohistochemistry (IHC) staining of rat penile tissues was used to validate several targets. Notably, the Cell Counting Kit‐8 assay, Western blotting, oxidative stress (OS) level, and iron concentration were tested in corpus cavernosum smooth muscle cells (CCSMCs) stimulated with high glucose (HG), and treated with Ferrostatin‐1 (Fer‐1).

Results

Sixty‐nine disease targets of DMED were identified. According to KEGG analysis, these targets were primarily enriched in the ferroptosis pathway. Additionally, IHC results revealed that the expression of GPX4, SLC7A11, and ACSL4 was deregulated in the DMED group compared to the control group. Significantly, HG decreased cell viability and increased OS and iron levels in CCSMCs, which could be reversed by Fer‐1 treatment.

Discussion and conclusion

Our study revealed that ferroptosis may indeed exist in DMED. GPX4, SLC7A11, and ACSL4 all have a role in controlling the viability of CCSMCs, making them potential therapeutic targets.