bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of mitochondrial energetics in the origin and diversification of eukaryotes
Authors: Schavemaker Paul E. , Muñoz-Gómez Sergio A.
Published: October 2021

The origin of eukaryotic cell size and complexity is thought by some to have required an energy excess provided by mitochondria, whereas others claim that mitochondria provide no energetic boost to eukaryotes. Recent observations show that energy demand scales continuously and linearly with cell volume across both prokaryotes and eukaryotes, and thus suggest that eukaryotes do not have an increased energetic capacity over prokaryotes. However, amounts of respiratory membranes and ATP synthases scale super-linearly with cell surface area. Furthermore, the energetic consequences of the contrasting genomic architectures between prokaryotes and eukaryotes have yet to be precisely quantified. Here, we investigated (1) potential factors that affect the cell volumes at which prokaryotes become surface area-constrained, (2) the amount of energy that is divested to increasing amounts of DNA due to the contrasting genomic architectures of prokaryotes and eukaryotes, and (3) the costs and benefits of respiring symbionts for a host cell. Our analyses suggest that prokaryotes are not necessarily constrained by their cell surfaces at cell volumes of 100–103 μm3, and that the genomic architecture of eukaryotes is only slightly advantageous at genomes sizes of 106–107 bp. This suggests that eukaryotes may have first evolved without the need for mitochondria as these ranges hypothetically encompass the Last Eukaryote Common Ancestor and its proto-eukaryotic ancestors. At these slightly larger cell volumes, a host cell may also have derived a greater advantage (lower cost) from harboring a population of ATP-producing symbionts. However, our analyses also show that increasingly larger and fast-dividing prokaryotes would have a shortage of surface area devoted to respiration and would disproportionally divest more energy to DNA synthesis at larger genome sizes. We thus argue that, even though mitochondria may not have been required by the first eukaryotes, the successful diversification of eukaryotes into larger and faster-growing cells was ultimately contingent upon the origin of mitochondria.

Significance

There has been a lot of theorizing about the evolution of eukaryotes from prokaryotes, but no consensus seems to be on the horizon. Our quantitative analyses on the required amount of respiratory membrane, and the amount of energy diverted to DNA synthesis, by both prokaryotes and eukaryotes, suggest that mitochondria provided rather small advantages to the first eukaryotes, but were advantageous for the macro-evolutionary diversification of eukaryotes. This conclusion provides a middle road in the debate between those that claim that the origin of eukaryotes required a massive energy boost provided by mitochondria, and those that argue that the origin of mitochondria did not represent a quantum leap in energetic advantages to eukaryotes.
Cancer cell-autonomous cGAS-STING response confers drug resistance
Authors: Lv Qian-Ming , Wang Shi-Yi , Lei Hui-Min , Zhang Ke-Ren , Tang Ya-Bin , Shen Ying , Lu Li-Ming , Chen Hong-Zhuan , Zhu Liang
Published: October 2021

As an evolutionarily conserved DNA-sensing machinery in innate immunity, the cGAS-STING pathway has been reported to play an important role in immune surveillance and tumor suppression. Recent evidence suggests an intriguing tumor- and metastasis-promoting effect of this signaling pathway, either in a cancer cell-autonomous or a cancer cell-nonautonomous, bystander cell-mediated manner. Here, we show a new face of cGAS-STING signaling whose activation in a cancer-cell-autonomous response manner confers drug resistance. Targeted or conventional chemotherapy drug treatment induced cancer cell cytosolic DNA accumulation and triggered subsequent cGAS-STING signaling activation in cancer cell lines and the human cell-derived xenograft tumors. This activation promoted an acquisition and maintenance of drug resistance which was prevented and overcome in vitro and in vivo by blockade of STING signaling. This finding highlights a new face of cGAS-STING signaling and an ability of cancer cells to hijack the evolutionarily conserved inflammatory signaling to counteract drug stress and warrants a caution in combining STING agonist with targeted or conventional chemotherapy drug treatment, a strategy prevailing in current clinical trials.

Statement of significance

cGAS-STING signaling has long been recognized as playing a key role in triggering antitumor immunity. We reveal a new face of cGAS-STING signaling and an ability of cancer cells autonomously to hijack the evolutionarily conserved inflammatory signaling to counteract drug stress.
SINBAD: a flexible tool for single cell DNA methylation data
Authors: Uzun Yasin , Yu Wenbao , Chen Changya , Tan Kai
Published: October 2021

DNA methylation is an epigenetic mark that has vital importance in both development and disease. Single cell bisulfite sequencing technologies enable profiling of the methylome at high resolution, providing the basis for dissecting the heterogeneity and dynamics of DNA methylation in complex tissues and over time. Despite the rapid increase in the number of experimental protocols for methylome sequencing, analytical tools designed specifically for single-cell data are lacking. We developed a computational tool, SINBAD, for efficient and standardized pre-processing, quality assessment and analysis of single cell methylation data. Starting from multiplexed sequencing reads, major analysis modules of SINBAD include preprocessing, read mapping, methylation quantification, multivariate analysis, and gene signature profiling. SINBAD provides a flexible platform to implement interoperable and robust processing of single-cell methylome data.
Previously uncharacterized rectangular bacterial structures in the dolphin mouth
Authors: Dudek Natasha K. , Galaz-Montoya Jesus G. , Shi Handuo , Mayer Megan , Danita Cristina , Celis Arianna I. , Viehboeck Tobias , Wu Gong-Her , Behr Barry , Bulgheresi Silvia , Huang Kerwyn Casey , Chiu Wah , Relman David A.
Published: October 2021

Much remains to be explored regarding the diversity of uncultured, host-associated microbes. Here, we report the discovery of unusual rectangular bacterial structures (RBSs) in the mouths of bottlenose dolphins. DNA staining revealed multiple paired bands within RBSs that suggested cells dividing along the longitudinal axis. Cryogenic transmission electron microscopy and tomography revealed parallel membrane-bound segments, suspected to be cells, encapsulated by an S-layer-like periodic surface covering. RBSs displayed novel pilus-like appendages with bundles of threads splayed at the tips. Multiple lines of evidence suggested that RBSs are bacterial and distinct from the Neisseriaceae generaSimonsiellaandConchiformibius, with which they share similar morphology and division patterning, including genomic DNA sequencing of micromanipulated RBSs, 16S rRNA gene sequencing, and fluorescencein situhybridization. Our findings highlight the diversity of novel microbial forms and lifestyles that await discovery and characterization using tools complementary to genomics such as microscopy.
Multiple paths lead to salt tolerance - pre-adaptation vs dynamic responses from two closely related extremophytes
Authors: Tran Kieu-Nga , Wang Guannan , Oh Dong-Ha , Larkin John C. , Smith Aaron P. , Dassanayake Maheshi
Published: October 2021

Salt tolerance is a complex trait with much of the underlying genetic variation and integrated response strategies yet to be discovered from stress adapted plants.Schrenkiella parvulaandEutrema salsugineumare salt-tolerant extremophytes related toArabidopsis thalianain Brassicaceae. We investigated their response strategies contrasted against the salt-sensitive model,A. thalianato cope with salt stresses via transcriptomic, metabolomic, and ionomic adjustments. The extremophytes exemplified divergent routes to achieve nutrient balance, build osmotolerance, boost antioxidant capacity, and extend transcriptomic support for modified ion transport and stress signaling. Those led to similar molecular phenotypes adapted to salt stress in the extremophytes, absent inA. thaliana. The predominant transcriptomic signals in all three species were associated with salt stress. However, root architecture modulation mediated by negative regulation of auxin and ABA signaling supported minimally-affected root growth unique to each extremophyte during salt treatments. Overall,E. salsugineumexhibited pre-adapted responses at the metabolome level, whereasS. parvulashowed dynamic metabolomic responses coupled to a pre-adapted transcriptome to survive salt stress. Our work shows that the two extremophytes share common salt tolerance features, but differ substantially in pathways leading to the convergent, adaptive traits.
The SKBR3 Cell-Membrane Proteome: Role in Aberrant Cancer Cell Proliferation and Resource for Precision Medicine Applications
Authors: Karcini Arba , Lazar Iulia M.
Published: October 2021

The plasma membrane proteome resides at the interface between the extra- and intra-cellular environment and through its various roles in signal transduction, immune recognition, nutrient transport, and cell-cell and cell-matrix interactions plays an absolutely critical role in determining the fate of a cell. Our work was aimed at exploring the landscape of the cancer cell-membrane proteome responsible for sustaining uncontrolled cell proliferation, and its intrinsic resources for enabling detection and therapeutic interventions. SKBR3/HER2+ breast cancer cells were used as a model system and mass spectrometry for characterizing the proteome. The number of identified cell-membrane proteins exceeded 2,000, with ~1,300 being matched by two or more unique peptides. Classification in four major categories, i.e., proteins with receptor or enzymatic activity, CD antigens, transporters, and cell adhesion proteins, uncovered overlapping roles in biological processes that drive cell growth, apoptosis, differentiation, immune response, adhesion and migration, as well as capabilities for signaling crosstalk and alternate pathways for proliferation. The large number of tumor markers (>50) and putative drug targets (>100) exposed a vast potential for yet unexplored detection and targeting opportunities, whereas the presence of 15 antigen immunological markers enabled an assessment of epithelial, mesenchymal or stemness characteristics. Serum-starved cells displayed altered processes related to mitochondrial OXPHOS/ATP synthesis, protein folding and localization, while serum-treated cells exhibited attributes that support tissue invasion and metastasis. Altogether, our findings advance the understanding of the biological triggers that sustain aberrant cancer cell proliferation, survival and development of resistance to therapeutic drugs, and reveal the vast innate opportunities for guiding immunological profiling and precision medicine applications aimed at target selection or drug discovery.
PU.1 expression defines distinct functional activities in the phenotypic HSC compartment in a mouse model of inflammatory stress
Authors: Chavez James S. , Rabe Jennifer L. , Hernandez Giovanny , Mills Taylor S. , Niño Katia E. , Davizon-Castillo Pavel , Pietras Eric M.
Published: October 2021

The transcription factor PU.1 is a critical regulator of lineage fate in blood-forming hematopoietic stem cells (HSC). In response to inflammatory signals, PU.1 expression is increased in HSC, activating myeloid differentiation genes while repressing cell cycle and protein synthesis genes. To address potential functional heterogeneity arising in the phenotypic HSC compartment due to changes in PU.1 expression, here we fractionated phenotypic HSC using the SLAM code in conjunction with PU.1 expression levels using the PU.1-EYFP reporter mouse strain. While PU.1lo SLAM cells contain extensive long-term repopulating activity and a molecular signature corresponding to HSC activity at steady state, under inflammatory conditions the PU.1lo SLAM fraction is comprised almost entirely of HSC-like cells containing extensive short-term megakaryocytic potential. Our data demonstrate that the phenotypic HSC gate is heterogenous, and that similar PU.1 transcription factor levels can be tied to distinct functional activities under steady-state and inflammatory conditions.
Chromosome-specific telomere lengths and the minimal functional telomere revealed by nanopore sequencing
Authors: Sholes Samantha L. , Karimian Kayarash , Gershman Ariel , Kelly Thomas J. , Timp Winston , Greider Carol W.
Published: October 2021

We developed a method to tag telomeres and measure telomere length by nanopore sequencing in the yeast S. cerevisiae. Nanopore allows long-read sequencing through the telomere, through the subtelomere, and into unique chromosomal sequence, enabling assignment of telomere length to a specific chromosome end. We observed chromosome end–specific telomere lengths that were stable over 120 cell divisions. These stable chromosome-specific telomere lengths may be explained by slow clonal variation or may represent a new biological mechanism that maintains equilibrium unique to each chromosome end. We examined the role of RIF1 and TEL1 in telomere length regulation and found that TEL1 is epistatic to RIF1 at most telomeres, consistent with the literature. However, at telomeres that lack subtelomeric Y′ sequences, tel1Δ rif1Δ double mutants had a very small, but significant, increase in telomere length compared with the tel1Δ single mutant, suggesting an influence of Y′ elements on telomere length regulation. We sequenced telomeres in a telomerase-null mutant (est2Δ) and found the minimal telomere length to be ∼75 bp. In these est2Δ mutants, there were apparent telomere recombination events at individual telomeres before the generation of survivors, and these events were significantly reduced in est2Δ rad52Δ double mutants. The rate of telomere shortening in the absence of telomerase was similar across all chromosome ends at ∼5 bp per generation. This new method gives quantitative, high-resolution telomere length measurement at each individual chromosome end and suggests possible new biological mechanisms regulating telomere length.
A preliminary investigation into senior management skills: the context of third-party logistics (3PLs) providers
Authors: Midgley James , Bak Ozlem
Published: October 2021

Purpose

The third-party logistics (3PL) provider has faced significant change since containerisation with the broadening scope of supply chains and technological developments. With these changes, the required supply chain skills discussions have covered mostly graduate skills or employees' skills with a limited discussion to what extent and whether senior management skills were changing. Hence, 3PL senior management skill requirements will be compiled based on existing studies and assessed to check whether these are still relevant and if so to what extent for today's 3PL senior managers.

Design/methodology/approach

A questionnaire has been devised based on 3PL senior management skills identified in the academic literature and sent out to senior managers via professional social networks of 3PL. Based on the previous literature, the senior managers selected had to fulfil the selection criteria of a minimum five years' managerial experience in a 3PL, and a minimum of ten years' experience in general, which limited the sample size to twenty-seven senior managers in the 3PL sector.

Findings

The findings indicated that 3PL senior managers’ skills highlighted an increasing dependence on and importance of relational and behavioural skills, particularly when compared with the more traditional functional and managerial skills. The study indicated that the 3PL senior managers highlighted an increasing dependence and importance upon relational and behavioural skills, particularly when compared with the more traditional functional skills.

Research limitations/implications

The study has explored the senior management skills in 3PL in the UK, albeit the respondents possessing diverse backgrounds. Therefore, it would be beneficial to test whether these findings are exemplary across the wider 3PL sector, not only in the UK but also across Europe to see how corporate agenda for executive supply chain skills could be devised.

Practical implications

Corporate supply chain training and development staff can develop specific programs based on the 3PL senior management skill sets especially on relational and behavioural skills, which are needed for future managers as well as up-skill senior managers' skills which are deemed to be most important in the current 3PL market.

Originality/value

This paper contributes to the supply chain skills discussion and reports subject relevant challenges for today’s senior management in the 3PL industry. The findings have generated preliminary discussions on whether senior management skills are changing with the broadening scope of supply chains.
Industry 4.0 and business process management: state of the art and new challenges
Authors: Bazan Patricia , Estevez Elsa
Published: October 2021

Purpose

The objective of the work is to analyze the impact of the Internet of Things (IoT) concepts and associated technologies in the framework of organizations and the management of their processes and how event orientation, as well as the structure of said business processes, can play an important role in this new organizational model. The main contribution of this work is to present a conceptualization of the research, identify approaches and challenges that require further study, and as a result, a proposal for future research.

Design/methodology/approach

The methodology comprises a qualitative analysis using secondary data. The approach relies on searches of scientific papers conducted in well-known databases, identifying research work around the IoT and Industry 4.0 applied to business process management. Based on the identified papers, the authors selected the most relevant and the latest publications, and categorized their contributions and findings based on open and selective coding. In total, the analysis is based on 95 papers that were selected and analyzed in depth.

Findings

The results of this research allow analyzing and ordering the existing contributions around Industry 4.0 and its impact on current organizations. The proposed conceptualization was derived from the analysis of the state of the research and identifies four categories: (1) improvements caused by Industry 4.0 and its impact on inter-organizational relations, (2) new architectural models and infrastructure of remote resources, their movement from the cloud to the edge and its effect on business processes, (3) context-aware concepts brought to business process management (BPM) linked to unstructured business processes and (4) complex event processing as a possible means for business processes sensitive to IoT signals.

Practical implications

The construction of current software ecosystems is strongly affected by the variety of information sources that feed them, as well as their volume. In addition, business processes represent organizations internally and are challenged to transcend the limits of companies due to the mentioned changes in software ecosystems. Industry 4.0 in conjunction with BPM re-defines the business process management paradigm and leads them to acquire the dynamism and sensitivity to the context that they usually did not have, as well as force them to move toward distributed platforms.

Originality/value

This paper assesses the state of the art in Industry 4.0 and business process management. The area can be defined as the intersection of two bigger areas highly relevant for organizations; on the one hand, the management and execution of business processes; and on the other hand, new conceptual, technological and methodological challenges to information systems that have to become more sensitive to event processing and also have to consume a large volume of data permanently and ubiquitously.
Institutional pressure, firm's green resources and green product innovation: evidence from Taiwan's electrical and electronics sector
Authors: Huang Yi-Chun , Chen Chih-Ta
Published: October 2021

Purpose

Integrating economic and green initiatives into firm strategies is a challenge for firms in various industries. The study aims to incorporate multiple views, i.e. green innovation theory (GIT), the green institutional perspective (GIP) and the natural-resource-based view (NRBV), to develop a comprehensive model to explore why and how firms implement green product innovation (GPI).

Design/methodology/approach

The study explores the relationships among institutional pressure, the firm's green resources and GPI. The research also distinguishes two different types of GPI: exploratory GPI and exploitative GPI. A total of 270 valid questionnaires were collected from electrical and electronics manufacturers in Taiwan. The authors employed structural equation modeling (SEM) using analysis of moment structures (AMOS) 23.0 to test the hypotheses.

Findings

The results show that institutional pressure has a significant positive correlation with the firm's green resources. Furthermore, institutional pressure has a significantly positive influence on exploratory GPI and exploitative GPI, respectively. The firm's green resources also have a significantly positive effect on both exploratory GPI and exploitative GPI. In addition, institutional pressures have significantly positive indirect effect on both exploratory GPI and exploitative GPI.

Research limitations/implications

Economic benefits and environmental sustainability are the most pressing issues faced by the electrical and electronics industry today. The study's investigation covers Taiwanese electrical and electronics manufacturers only, so the test of the research model has limited generalizability. The authors suggest that to expand the generalizability of the findings, future research should examine this model in the context of other regions such as Southeast Asia, Africa, South America, etc.

Practical implications

The study has many interesting implications for both practitioners and policymakers. The authors' findings suggest that while Taiwanese electrical and electronics manufacturers face significant pressure from customers, competitors and regulation requirements (e.g. waste electrical and electronic equipment [WEEE], restriction of hazardous substances [RoHS] and energy using product [EuP] directives), firms in that sector should efficiently and effectively deploy their green resources and then perform proper GPI (e.g. exploratory GPI or exploitative GPI). These results also serve as a reminder to policymakers that balancing coercive (command-and-control) mechanisms with incentives and voluntary mechanisms is the best means by which to develop motivational and effective GPI policies.

Originality/value

First and foremost, the paper divides GPI into exploratory GPI and exploitative GPI. Furthermore, the research incorporates two important schools of thought, i.e. the GIP and NRBV, thus providing a more holistic view by which to explore why and how companies adopt GPI.
Localizing the Sustainable Development Goals: a managerial perspective
Authors: Guarini Enrico , Mori Elisa , Zuffada Elena
Published: October 2021

Purpose

This article investigates how Sustainable Development Goals (SDGs) can be integrated into the strategic planning and management processes of local governments (LGs). It draws from the classic strategic planning and control framework developed in management studies and elaborates some propositions for adapting, implementing and monitoring the SDGs at the city level.

Design/methodology/approach

As a first step in the assessment of the ways the principles of sustainable development can be integrated into LG management, this research scrutinizes the incorporation of sustainability goals in the strategic plans of all medium-to-large capital cities of provinces in Italy, a context in which there has been a National Strategy for Sustainable Development (NSSD) since 2016.

Findings

The focus on SDGs at the LG level in Italy is in its initial stage, and few capital cities have started to integrate sustainable development concerns into their comprehensive strategic plans. SDGs are used mainly as a reference framework in the strategic plans to demonstrate the contribution of LG strategies to global concerns on sustainable development.

Practical implications

The paper offers insights for political leaders and public managers to rethink their strategic management systems, including the continuous process of evaluating and updating of strategic plans, in accordance with the multidimensional perspective of sustainability. To this end, the study has identified possible patterns of actions that public managers elsewhere will find useful.

Originality/value

The managerial approach behind the proposed conceptual framework might contribute to effectively localize the SDGs in multilevel government settings and to integrate the concept of sustainability as a guiding principle into organizational routines.
Toward a typology of weak-signal early alert systems: functional early warning systems in the post-COVID age
Authors: Černý Jan , Potančok Martin , Castro Hernandez Elias
Published: October 2021

Purpose

The study aims to expand on the concept of an early warning system (EWS) by introducing weak-signal detection, human-in-the-loop (HIL) verification and response tuning as integral parts of an EWS's design.

Design/methodology/approach

The authors bibliographically highlight the evolution of EWS over the last 30+ years, discuss instances of EWSs in various types of organizations and industries and highlight limitations of current systems.

Findings

Proposed system to be used in the transforming of weak signals to early warnings and associated weak/strong responses.

Originality/value

The authors contribute to existing literature by presenting (1) novel approaches to dealing with some of the well-known issues associated with contemporary EWS and (2) an event-agnostic heuristic for dealing with weak signals.

Peer review

The peer review history for this article is available at:https://publons.com/publon/10.1108/OIR-11-2020-0513.
Function of a multimodal signal: A multiple hypothesis test using a robot frog
Authors: Caldart Vinícius Matheus , dos Santos Mauricio Beux , Machado Glauco
Published: October 2021

Multimodal communication may evolve because different signals may convey information about the signaller (content‐based selection), increase efficacy of signal processing or transmission through the environment (efficacy‐based selection), or modify the production of a signal or the receiver's response to it (inter‐signal interaction selection).

To understand the function of a multimodal signal (aggressive calls + toe flags) emitted by males of the frog Crossodactylus schmidti during territorial contests, we tested two hypotheses related to content‐based selection (quality and redundant signal), one related to efficacy‐based selection (efficacy backup), and one related to inter‐signal interaction selection (context). For each hypothesis we derived unique predictions based on the biology of the study species.

In a natural setting, we exposed resident males to a robot frog simulating aggressive calls (acoustic stimulus) and toe flags (visual stimulus), combined and in isolation, and measured quality‐related traits from males and local levels of background noise and light intensity.

Our results provide support to the context hypothesis, as toe flags (the context signal) are insufficient to elicit a receiver's response on their own. However, when toe flags are emitted together with aggressive calls, they evoke in the receiver qualitatively and quantitatively different responses from that evoked by aggressive calls alone. In contrast, we found no evidence that toe flags and aggressive calls provide complementary or redundant information about male quality, which are key predictions of the quality and redundant signal hypotheses respectively. Finally, the multimodal signal did not increase the receiver's response across natural gradients of light and background noise, a key prediction of the efficacy backup hypothesis.

Toe flags accompanying aggressive calls seem to provide contextual information that modify the receiver's response in territorial contests. We suggest this contextual information is increased motivation to escalate the contest, and discuss the benefits to the signallers and receivers of adding a contextual signal to the aggressive display. Examples of context‐dependent multimodal signals are rare in the literature, probably because most studies focus on single hypotheses assuming content‐ or efficacy‐based selection. Our study highlights the importance of considering multiple selective pressures when testing multimodal signal function.
Doing the right thing: HRM in the performing arts
Authors: Opara Stanley , Stanton Pauline
Published: October 2021

This article reports on a qualitative study exploring HRM practices in three Australian performing arts companies of different sizes. We focus on the strength of the HRM system by exploring the concepts of distinctiveness, consistency and consensus from the perspectives of key stakeholders. We found, first, weak and largely invisible HR systems in all three companies due to an industry focused on financial survival, project‐based work and a highly casualised labour force. Second, complex and precarious employment modes exist in each organisation which challenge the HR architecture debate in regard to strategic value and uniqueness of core and peripheral employees. Third, a strong commitment to regulatory compliance by organisations to protect their employees demonstrates that HRM practices are relevant in the performing arts. Finally, we suggest that performing artists might be more committed to their craft and industry than to the organisation, which creates challenges for HRM practice in this sector.
How the organizational ethical climate accounts for employee voice behavior: a multilevel analysis
Authors: Wang Hsing‐Kuo , Yen Yu‐Fang
Published: October 2021

This study adopted social identity theory to explore the mediating effect of organizational identification on the relationship between the organizational ethical climate and employee voice behavior. Additionally, it examined the cross‐level effects of the organizational ethical climate on employee voice behavior. We used a survey‐based methodology to collect data from 232 employees and 48 managers of service firms in Taiwan. Hierarchical linear modeling analysis was used to test the hypotheses. Our findings indicate the importance of the organizational ethical climate in enhancing organizational identification, which in turn is positively related to employee voice behavior. Thus, employees who perceive an organizational ethical climate identify more strongly with organizations and are more willing to generate voice behavior.
Metabolic engineering of Saccharomyces cerevisiae for hydroxytyrosol overproduction directly from glucose
Authors: Bisquert Ricardo , Planells‐Cárcel Andrés , Valera‐García Elena , Guillamón José Manuel , Muñiz‐Calvo Sara
Published: October 2021

Hydroxytyrosol (HT) is one of the most powerful dietary antioxidants with numerous applications in different areas, including cosmetics, nutraceuticals and food. In the present work, heterologous hydroxylase complex HpaBC from Escherichia coli was integrated into the Saccharomyces cerevisiae genome in multiple copies. HT productivity was increased by redirecting the metabolic flux towards tyrosol synthesis to avoid exogenous tyrosol or tyrosine supplementation. After evaluating the potential of our selected strain as an HT producer from glucose, we adjusted the medium composition for HT production. The combination of the selected modifications in our engineered strain, combined with culture conditions optimization, resulted in a titre of approximately 375 mg l−1 of HT obtained from shake‐flask fermentation using a minimal synthetic‐defined medium with 160 g l−1 glucose as the sole carbon source. To the best of our knowledge, this is the highest HT concentration produced by an engineered S. cerevisiae strain.
Impact of tumor size and location on lung dose difference between stereotactic body radiation therapy techniques for non‐small cell lung cancer
Authors: Jang Seong Soon , Shin Yohan , Park Suk Young , Huh Gil Ja , Yang Young Jun
Published: October 2021

Background

To evaluate the lung dose differences between three‐dimensional conformal radiotherapy (3D‐CRT) and intensity‐modulated radiation therapy (IMRT) techniques for lung stereotactic body radiation therapy (SBRT) and the correlations with tumor characteristics, such as size and location.

Methods

Dosimetric comparisons between the two SBRT techniques in high‐ and low‐ to intermediate‐dose regions were retrospectively performed using four planning indices and lung‐dose parameters in 31 lung tumors. The magnitude of differences in these parameters was analyzed with relation to the planning target volume (PTV) and location‐related parameters.

Results

The absolute differences between the two techniques in lung‐dose parameters were small in both ipsilateral and bilateral lungs. The dosimetric differences were mainly correlated with the PTV rather than location‐related parameters, with positive and negative correlations with the high‐dose and intermediate‐dose parameters, respectively. The distances from the ipsilateral lung centroid to the PTV center were not correlated with the differences in any of the lung‐dose parameters. Additionally, the negative correlations with the MLD and V20 differences disappeared after applying a more rapid dose fall‐off in the IMRT plans for tumors with small PTVs of ≤15 cc.

Conclusions

Lung dose differences between the 3D‐CRT and IMRT techniques for lung SBRT were mainly correlated with the PTV rather than location‐related parameters. Together with the dosimetric benefit in high‐dose lung regions of IMRT for larger tumors, the relative increases in the MLD and V20 for small‐sized tumors could be reduced by applying a more rapid dose fall‐off outside the PTV.
The risk of dementia in patients using psychotropic drugs: Antidepressants, mood stabilizers or antipsychotics
Authors: Tournier Marie , Pambrun Elodie , Maumus‐Robert Sandy , Pariente Antoine , Verdoux Hélène
Published: October 2021

Objective

The risk of dementia associated with the use of psychotropic drugs is not fully understood. A nested case‐control study was carried out to assess the risk of dementia broadly defined or Alzheimer's disease associated with antidepressants, mood stabilizers or antipsychotics.

Methods

A cohort was formed from healthcare claim databases including all patients aged 50 and over with a first dispensing of the psychotropic drugs concerned between 2006 and 2017. Patients who developed dementia over the study period were considered as cases. The association between drug exposure prior to a five‐year lag time and diagnosis of dementia was assessed by conditional logistic regression models.

Results

No association was found between dementia, either broadly defined or Alzheimer disease, and antidepressant or mood stabilizers. Findings were conflicting with regard to antipsychotics. First‐ and second‐generation antipsychotics (FGA and SGA) were not associated with Alzheimer disease. SGA treatments of more than 3 months were associated with a higher risk of dementia broadly defined than no use of antipsychotics (Odds ratio [OR] 2.00; 95%CI 1.06–3.79; p = 0.03). In a sensitivity analysis using a lag time of 3 years, ever use of SGA and SGA treatments of more than 3 months were associated with a higher risk of dementia broadly defined than no use of antipsychotics (OR 1.71; 1.10–2.67; p = 0.02 and OR 1.84; 1.03–3.32; p = 0.04, respectively).

Conclusion

The association between antipsychotics and dementia should be further investigated to establish patients, specific drugs, and patterns of treatment at risk. Prescribers should remain cautious when prescribing them.
Trap type affects dung beetle taxonomic and functional diversity in Bornean tropical forests
Authors: Ong Xin Rui , Hemprich‐Bennett David , Gray Claudia L. , Kemp Victoria , Chung Arthur Y. C. , Slade Eleanor M.
Published: October 2021

Baited pitfall traps (BPTs) and flight intercept traps (FITs) are the most common methods employed for sampling dung beetle communities. These methods vary in their efficacy and are affected by factors such as the bait types used and the dispersal abilities of different dung beetle species. We present the first quantitative comparison of the community composition, taxonomic and functional diversity of dung beetles caught in human dung BPTs and FITs in Bornean tropical forests. Functional diversity metrics were calculated based on the three functional traits of nesting method, body length, and diel activity. We show that BPTs and FITs captured complementary communities with different functional traits, and that BPTs captured more functionally diverse communities. We therefore recommend using a combination of both BPTs and FITs for studies assessing the composition of dung beetles across habitat types. Our results also highlight that it is important to consider how trap type affects the trait composition of communities when relating dung beetle communities and functional traits to ecological functioning. We suggest modifications to FITs based on the design of harp traps to increase their effectiveness in capturing larger‐bodied beetles.
The value of the basophil activation test in the evaluation of patients reporting allergic reactions to the BNT162b2 mRNA COVID‐19 vaccine
Authors: Labella Marina , Céspedes Jose Antonio , Doña Inmaculada , Shamji Mohamed H. , Agache Ioana , Mayorga Cristobalina , Torres Maria José
Published: October 2021

Background

mRNA‐based COVID‐19 vaccines have been reported to induce hypersensitivity reactions (HSR) in a small number of individuals. We aimed to evaluate the real‐world incidence of the BNT162b2 mRNA COVID‐19 vaccine HSR and to determine the value of the basophil activation test (BAT) in the allergological workup of patients reporting these reactions.

Methods

We prospectively enrolled patients with a clinical history indicative of HSR to the BNT162b2 mRNA COVID‐19 vaccine. The allergological workup included skin testing (STs) and BAT with polyethylene glycol (PEG) and the vaccine. In those with negative allergy assessments, the administration of the second dose of the BNT162b2 mRNA COVID‐19 vaccine was offered.

Results

Seventeen adults were included. Eleven cases (64.7%) tested negative in the allergological workup and tolerated the re‐administration of the second dose of the vaccine and considered non‐allergic. Six cases (35.3%) were considered allergic and classified into three groups: 2 subjects displayed positive STs and/or BAT to PEG (Group A), two individuals displayed positive BAT to the vaccine (Group B), and in 2 patients with moderate or severe reactions, the culprit was not identified, tested negative to STs and BAT to both PEG and vaccine (Group C). We further evaluated the value of BAT when the results were positive to the vaccine and negative to PEG by performing BAT in controls groups, finding positive BAT results in 50% of controls, all of them recovered from COVID‐19 infection. In contrast, BAT was negative in patients who had not suffered from COVID‐19 disease.

Conclusions

BAT can be used as a potential diagnostic tool for confirming allergy to PEG excipient but not to the vaccine as a positive result in BAT may indicate a past COVID‐19 infection instead of an allergy.
Prevalence of congenital cryptorchidism in Estonia
Authors: Kübarsepp Viljo , Varik Karin , Varendi Heili , Antson Anne , Veinla Maie , Nellis Georgi , Merila Mirjam , Salundi Urve , Astover Valve , Punab Margus
Published: October 2021

Background

Cryptorchidism is one of the most common urogenital malformations. Cryptorchidism prevalence varies greatly in different countries and populations. The aim of the current study was to determine and analyse cryptorchidism prevalence in Estonia.

Materials and methods

During 2012–2015, all consecutively born 5014 boys at Tartu University Hospital were examined for cryptorchidism. All the subjects with cryptorchidism were followed up for at least 6 months to assess spontaneous testicular descent.

Results

Note that 2.1% cases had one or both testicles undescended at birth, 1.6% cases at expected date of birth, 1% cases at 3 months of age, and 0.8% cases at the age of 6 months had cryptorchidism. Cryptorchidism prevalence at birth was higher in preterm boys (11.9%), boys of low birth weight (16.7%) and boys small for gestational age (14%) but was lower in full‐term newborn boys (1.1%). During follow‐up, testes descended spontaneously in 61.6% of boys, more commonly in prematurely born boys (92%) and boys with low gestational weight (93%) as compared to full‐term cryptorchid boys (29.2%) and cryptorchid boys with normal birth weight (34%). At the age of 6 months, cryptorchidism prevalence was equalized in preterm boys (0.9%) and boys with low birth weight (1%) as compared to full‐term boys (0.7%) and boys with normal birth weight (0.7%). Boys SGA required surgical intervention more commonly than boys with normal birth weight. Ethnically, cryptorchidism prevalence at birth was similar among Estonians and non‐Estonians.

Conclusion

Our data revealed that cryptorchidism prevalence, especially in full‐term boys, is lower in Estonia than reported in the other Nordic‐Baltic countries and worldwide.
Editorial: lymphocytic gastritis and its relationships with other gastrointestinal disorders—authors’ reply
Authors: Genta Robert M. , Sonnenberg Amnon
Published: October 2021

LINKED CONTENT

This article is linked to Genta et al and Annibale & Falangone papers. To view these articles, visit https://doi.org/10.1111/apt.16621 and https://doi.org/10.1111/apt.16653
Editorial: the never‐ending story—Helicobacter pylori and peptic ulcer disease. Authors' reply
Authors: Jiang Fang , Guo Chuan‐Guo , Leung Wai K.
Published: October 2021

LINKED CONTENT

This article is linked to Jiang et al and Sugano & Howden papers. To view these articles, visit https://doi.org/10.1111/apt.16604 and https://doi.org/10.1111/apt.16617
Source‐to‐sink: Regional grain size trends to reconstruct sediment budgets and catchment areas
Authors: Michael Nikolaos A. , Zühlke Rainer
Published: October 2021

Source‐to‐sink studies and calculating sediment budgets of ancient systems are important approaches for basin analysis. Because of the enormous scale of basins, most existing studies depend on subsurface datasets. As drilling campaigns focus on structural highs or specific trap types, well datasets cover only limited subareas of entire sedimentary basins. Outcrop studies are almost always based on even more spatially limited datasets. The ramifications for basin analysis are considerable: (1) actual sediment budgets are underestimated; (2) catchment denudation rates and sizes are miscalculated; (3) predicted net:gross ratios in sink areas bear high uncertainties. This paper outlines a new workflow‐defined approach to reconstruct regional grain size profiles to better estimate sediment budgets across an entire sedimentary basin, even when datasets have spatial limited coverage. The workflow includes compilation of grain size data, transformation to mass balance frameworks, and lateral matching of local to regional grain size profiles. The approach was tested on two representative continental‐to‐marine delta systems which are covered by four spatially limited datasets while the entire sedimentary basin (sink area) is much larger. The original estimates account for only maximum 40% of the actual total sediment volume as analysed with the new approach. The new method provides significantly improved constraints for catchment (source) models as well as input parameters (sediment budget, input locations, fractions) for process‐based depositional modelling for predictions of net:gross and detailed facies proximal to distal relationships. General benefits include lower uncertainties in clastic reservoir quality prediction (hydrocarbon exploration) and provenance analysis (fundamental research).
Novel LAMC2 fusion protein has tumor‐promoting properties in ovarian carcinoma
Authors: Daisuke Hoshino , Kato Hisamori , Fukumura Kazuhiro , Mayeda Akila , Miyagi Yohei , Seiki Motoharu , Koshikawa Naohiko
Published: October 2021

Laminins are heterotrimeric ECM proteins composed of α, β, and γ chains. The γ2 chain (Lm‐γ2) is a frequently expressed monomer and its expression is closely associated with cancer progression. Laminin‐γ2 contains an epidermal growth factor (EGF)‐like domain in its domain III (DIII or LEb). Matrix metalloproteinases can cleave off the DIII region of Lm‐γ2 that retains the ligand activity for EGF receptor (EGFR). Herein, we show that a novel short form of Lm‐γ2 (Lm‐γ2F) containing DIII is generated without requiring MMPs and chromosomal translocation between LAMC2 on chromosome 1 and NR6A1 gene locus on chromosome 9 in human ovarian cancer SKOV3 cells. Laminin‐γ2F is expressed as a truncated form lacking domains I and II, which are essential for its association with Lm‐α3 and ‐β3 chains of Lm‐332. Secreted Lm‐γ2F can act as an EGFR ligand activating the EGFR/AKT pathways more effectively than does the Lm‐γ2 chain, which in turn promotes proliferation, survival, and motility of ovarian cancer cells. LAMC2‐NR6A1 translocation was detected using in situ hybridization, and fusion transcripts were expressed in ovarian cancer cell tissues. Overexpression and suppression of fusion transcripts significantly increased and decreased the tumorigenic growth of cells in mouse models, respectively.

To the best of our knowledge, this is the first report regarding a fusion gene of ECM showing that translocation of LAMC2 plays a crucial role in the malignant growth and progression of ovarian cancer cells and that the consequent product is a promising therapeutic target against ovarian cancers.
Predictive value of EGFR mutation in non–small‐cell lung cancer patients treated with platinum doublet postoperative chemotherapy
Authors: Takahashi Toshiaki , Sakai Kazuko , Kenmotsu Hirotsugu , Yoh Kiyotaka , Daga Haruko , Ohira Tatsuo , Ueno Tsuyoshi , Aoki Tadashi , Hayashi Hidetoshi , Yamazaki Koji , Hosomi Yukio , Chen‐Yoshikawa Toyofumi F. , Okumura Norihito , Takiguchi Yuichi , Sekine Akimasa , Haruki Tomohiro , Yamamoto Hiromasa , Sato Yuki , Akamatsu Hiroaki , Seto Takashi , Saeki Sho , Sugio Kenji , Nishio Makoto , Inokawa Hidetoshi , Yamamoto Nobuyuki , Nishio Kazuto , Tsuboi Masahiro
Published: October 2021

The mutation status of tumor tissue DNA (n = 389) of resected stage II‐III non‐squamous non–small‐cell lung cancer (Ns‐NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG‐TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation‐positive status had a significantly shorter recurrence‐free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22‐2.21; P = .0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30‐2.44; P = .0003 for disease stage; and HR, 1.57; 95% CI, 1.15‐2.16; P = .0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II‐III Ns‐NSCLC patients. This result supports a role for mandatory molecular diagnosis of early‐stage Ns‐NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum‐based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).