bluuebunny/crossref_metadata_2025 huggingface dataset:
GABA-receptors are a new druggable target for limiting disease severity, lung viral load, and death in SARS-CoV-2 infected mice
Authors: Tian Jide , Dillion Barbara J. , Henley Jill , Comai Lucio , Kaufman Daniel L.
Published: June 2022

GABA-receptors (GABA-Rs) are well-known neurotransmitter receptors in the central nervous system. GABA-Rs are also expressed by immune cells and lung epithelial cells and GABA-R agonists/potentiators reduce inflammatory immune cell activities and limit acute lung injuries. Notably, plasma GABA levels are reduced in hospitalized COVID-19 patients. Hence, GABA-R agonists may have therapeutic potential for treating COVID-19. Here, we show that oral GABA treatment initiated just after SARS-CoV-2 infection, or 2 days later near the peak of lung viral load, reduced disease severity, lung coefficient index, and death rates in K18-hACE2 mice. GABA-treated mice had a reduced viral load in their lungs and displayed shifts in their serum cytokine and chemokine levels that are associated with better outcomes in COVID-19 patients. Thus, GABA-R activation had multiple beneficial effects in this mouse model which are also desirable for the treatment of COVID-19. A number of GABA-R agonists are safe for human use and can be readily tested in clinical trials with COVID-19 patients. We also discuss their potential for limiting COVID-19-associated neuroinflammation.
Copy number flexibility facilitates heteroresistance to increasing antibiotic pressure and threatens the beta-lactam pipeline
Authors: Choby Jacob E. , Ozturk Tugba , Abbott Carter N. , Nnabuife Christina , Colquhoun Jennifer M. , Satola Sarah W. , Rather Philip N. , Palzkill Timothy , Weiss David S.
Published: June 2022

It is unclear how bacteria rapidly adapt to resist novel drugs upon their introduction. Heteroresistance (HR) is a form of antibiotic resistance where a phenotypically unstable minority resistant subpopulation co-exists with a susceptible population. We observed HR to cefiderocol, a novel beta-lactam developed to resist beta-lactamases including extended-spectrum-beta-lactamases (ESBLs), among clinical isolates collected before its use. The resistant subpopulation inEnterobacterwas a continuum; increasing gene copy number of an otherwise ineffective ESBL mediated increased resistance in decreasing numbers of cells. The factors that control the magnitude of amplification are unclear. We observed that ESBL activity controlled the level of amplification, thus increased copy number can compensate for poor enzymatic activity. AKlebsiellaisolate from a clinical treatment failure also demonstrated amplification, highlighting the relevance of this phenomenon. These data provide insights into factors controlling dynamics of HR and how bacteria use phenotypic resistance to flexibly confront new antibiotic threats.
Altered tRNA processing is linked to a distinct and unusual La protein in Tetrahymena thermophila
Authors: Kerkhofs Kyra , Garg Jyoti , Fafard-Couture Étienne , Abou Elela Sherif , Scott Michelle , Pearlman Ronald E. , Bayfield Mark A.
Published: June 2022

Nascent pre-tRNAs are transcribed by RNA polymerase III and immediately bound by La proteins on the UUU-3’OH sequence, using a tandem arrangement of the La motif and an adjacent RNA recognition motif-1 (RRM1), resulting in protection from 3’-exonucleases and promotion of pre-tRNA folding. The Tetrahymena thermophila protein Mlp1 has been classified as a genuine La protein, despite the predicted absence of the RRM1. We found that Mlp1 functions as a La protein through binding of pre-tRNAs and affecting processing in Tetrahymena thermophila and when expressed in fission yeast. However, unlike in other examined eukaryotes, depletion of Mlp1 results in 3’-trailer stabilization. We also observed that 3’-trailers in Tetrahymena thermophila are uniquely short relative to other examined eukaryotes, and that 5’-leaders have evolved to disfavour pre-tRNA leader/trailer pairing. Our data indicate that this variant Mlp1 architecture is linked to an altered, novel mechanism of tRNA processing in Tetrahymena thermophila.
Epistasis between promoter activity and coding mutations shapes gene evolvability
Authors: Cisneros Angel F. , Gagnon-Arsenault Isabelle , Dubé Alexandre K. , Després Philippe C. , Kumar Pradum , Lafontaine Kiana , Pelletier Joelle N. , Landry Christian R.
Published: June 2022

The evolution of protein-coding genes proceeds as mutations act on two main dimensions: regulation of transcription level and the coding sequence. The extent and impact of the connection between these two dimensions are largely unknown because they have generally been studied independently. By measuring the fitness effects of all possible mutations on a protein complex at various levels of promoter activity, we show that expression at the optimal level for the WT protein masks the effects of both deleterious and beneficial coding mutations. Mutants that are deleterious at low expression but masked at optimal expression are slightly destabilizing for individual subunits and binding interfaces. Coding mutations that increase protein abundance are beneficial at low expression but incur a fitness cost at high expression. We thereby demonstrate that expression level can dictate which coding mutations are beneficial or deleterious.
A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging
Authors: Borg Raymond E. , Ozbakir Harun F. , Xu Binzhi , Li Eugene , Fang Xiwen , Peng Huan , Chen Irene A. , Mukherjee Arnab
Published: June 2022

The ability to noninvasively detect bacteria at any depth inside opaque tissues has important applications ranging from infection diagnostics to tracking therapeutic microbes in their mammalian host. Current examples of probes for detecting bacteria with strain-type specificity are largely based on optical dyes, which cannot be used to examine bacteria in deep tissues due to the physical limitation of light scattering. Here, we describe a new biomolecular probe for visualizing bacteria in a cell-type specific fashion using magnetic resonance imaging (MRI). The probe is based on a peptide that selectively binds manganese and is attached in high numbers to the capsid of filamentous phage. By genetically engineering phage particles to display this peptide, we are able to bring manganese ions to specific bacterial cells targeted by the phage, thereby producing MRI contrast. We show that this approach allows MRI-based detection of targeted E. coli strains while discriminating against non-target bacteria as well as mammalian cells. By engineering the phage coat to display a protein that targets cell surface receptors in V. cholerae, we further show that this approach can be applied to image other bacterial targets with MRI. Finally, as a preliminary example of in vivo applicability, we demonstrate MR imaging of phage-labeled V. cholerae cells implanted subcutaneously in mice. The nanomaterial developed here thus represents a path towards noninvasive detection and tracking of bacteria by combining the programmability of phage architecture with the ability to produce three- dimensional images of biological structures at any arbitrary depth with MRI.
The substitutions L50F, E166A and L167F in SARS-CoV-2 3CLpro are selected by a protease inhibitorin vitroand confer resistance to nirmatrelvir
Authors: Jochmans Dirk , Liu Cheng , Donckers Kim , Stoycheva Antitsa , Boland Sandro , Stevens Sarah K , De Vita Chloe , Vanmechelen Bert , Maes Piet , Trüeb Bettina , Ebert Nadine , Thiel Volker , De Jonghe Steven , Vangeel Laura , Bardiot Dorothée , Jekle Andreas , Blatt Lawrence M , Beigelman Leonid , Symons Julian A , Raboisson Pierre , Chaltin Patrick , Marchand Arnaud , Neyts Johan , Deval Jerome , Vandyck Koen
Published: June 2022

The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle and is a therapeutic target for the treatment of COVID-19. The potential of 3CLpro-inhibitors to select for drug-resistant variants needs to be established. Therefore, SARS-CoV-2 was passagedin vitroin the presence of increasing concentrations of ALG-097161, a probe compound designed in the context of a 3CLpro drug discovery program. We identified a combination of amino acid substitutions in 3CLpro (L50F E166A L167F) that is associated with > 20x increase in EC50values for ALG-097161, nirmatrelvir (PF-07321332) and PF-00835231. While two of the single substitutions (E166A and L167F) provide low-level resistance to the inhibitors in a biochemical assay, the triple mutant results in the highest levels of resistance (6x to 72x). All substitutions are associated with a significant loss of enzymatic 3CLpro activity, suggesting a reduction in viral fitness. Structural biology analysis indicates that the different substitutions reduce the number of inhibitor/enzyme interactions while the binding of the substrate is maintained. These observations will be important for the interpretation of resistance development to 3CLpro inhibitors in the clinical setting.

Abstract Importance

Paxlovid is the first oral antiviral approved for treatment of SARS-CoV-2 infection. Antiviral treatments are often associated with the development of drug resistant viruses. In order to guide the use of novel antivirals it is essential to understand the risk of resistance development and to characterize the associated changes in the viral genes and proteins. In this work, we describe for the first time a pathway that allows SARS-CoV-2 to develop resistance against Paxlovidin vitro. The characteristics ofin vitroantiviral resistance development may be predictive for the clinical situation. Therefore, our work will be important for the management of COVID-19 with Paxlovid and next generation SARS-CoV-2 3CLpro inhibitors.
Within-host diversity improves phylogenetic and transmission reconstruction of SARS-CoV-2 outbreaks
Authors: Ortiz Arturo Torres , Kendall Michelle , Storey Nathaniel , Hatcher James , Dunn Helen , Roy Sunando , Williams Rachel , Williams Charlotte , Goldstein Richard A. , Didelot Xavier , Harris Kathryn , Breuer Judith , Grandjean Louis
Published: June 2022

Accurate inference of who infected whom in an infectious disease outbreak is critical for the delivery of effective infection prevention and control. The increased resolution of pathogen whole-genome sequencing has significantly improved our ability to infer transmission events. Despite this, transmission inference often remains limited by the lack of genomic variation between the source case and infected contacts. Although within-host genetic diversity is common among a wide variety of pathogens, conventional whole-genome sequencing phylogenetic approaches to reconstruct outbreaks exclusively use consensus sequences, which consider only the most prevalent nucleotide at each position and therefore fail to capture low frequency variation within samples. We hypothesized that including within-sample variation in a phylogenetic model would help to identify who infected whom in instances in which this was previously impossible. Using whole-genome sequences from SARS-CoV-2 multi-institutional outbreaks as an example, we show how within-sample diversity is stable among repeated serial samples from the same host, is transmitted between those cases with known epidemiological links, and how this improves phylogenetic inference and our understanding of who infected whom. Our technique is applicable to other infectious diseases and has immediate clinical utility in infection prevention and control.
Generation of inheritable A-to-G transitions using adenine base editing and NG-PAM Cas9 in Arabidopsis thaliana
Authors: Tan Yi Yun , Liew Yin Yin , Castel Baptiste , Zhang Yizhong , Kim Sang-Tae , Chae Eunyoung
Published: June 2022

CRISPR/Cas9 technology is an important tool for functional genomics and crop improvement. It can be used to generate mutations at precise positions in the genome. Base editors consist of deaminase components and Cas9 to specify the type of mutation, such as C-to-T (cytosine base editors) or A-to-G (adenine base editors) transition. Available adenine base editor vectors usually make use of canonical Cas9, which limits their use to 5’-NGG-3’ containing targets. We combined a relaxed variant of SpCas9 that uses 5’-NG-3’ containing targets with the adenine base editor containing TadA7.10 or TadA8e to make a set of vectors. By using a phenotype-based screen, we found that our vectors efficiently induce A-to-G somatic mutations in a 5’-NGG-3’ PAM context in Arabidopsis thaliana up to 81% efficiency. Such mutations are inheritable at the homozygous stage in T2. Among tested vectors, pECNUS4 (Addgene #184887), which carries TadA8e, showed highest efficiency at generating a stable A-to-G transition in a 5’-NGH-3’ PAM context in the gene DM3. Using this vector, we were able to recreate a naturally occurring allele of DM3 in two generations without the transgene. pECNUS4 is a new component of the CRISPR toolbox to be used for introducing desired adenine base transitions with an expanded target window for functional genomic research and trait improvement.
Approach to electrochemical modulating differential extended X-ray absorption fine structure
Authors: Xu Wenjie , Zhang Guikai , Shou Hongwei , Zhou Jia , Chen Shuangming , Chu Shengqi , Zhang Jing , Song Li
Published: June 2022

The differential XAFS technique holds promise for detecting surface changes, which benefits many chemical applications. Phase-sensitive detection (PSD) analysis based on modulated excitation spectroscopy experiments is expected to obtain a high-quality difference spectrum, while the mathematical relationship and experiment parameters remain to be discussed. In this article, an approach to obtaining the difference spectrum from the PSD demodulated spectrum is described and its applicability in different experiment settings is discussed. The results indicate that the demodulated spectrum is almost equal to the difference spectrum when the modulating period is 20 times larger than the relaxation time constant. This approach was subsequently applied to an electrochemical modulation experiment and the demodulated spectrum was analyzed. A reversible lattice shrinking is observed via the fitting of demodulated spectra, which is proportional to the charge amount on the electrode. This approach could be used to quantitatively analyze the modulated excitation XAS data and holds promise for a wide range of electrochemical studies.
The influence of leadership styles and human resource management on educators' well-being in the light of three Sustainable Development Goals
Authors: Gallego-Nicholls Jose Fernando , Pagán Esther , Sánchez-García Javier , Guijarro-García María
Published: June 2022

Purpose

This paper analyzes the influence of leadership styles and human resource management (HRM) on teacher well-being and how these contribute to Sustainable Development Goals (SDGs) 3: Good Health and Well-being, 4: Quality Education, and 8: Decent Work and Economic Growth. The analysis assesses the extent to which the well-being of schoolteachers is influenced by the human resource management and leadership style of the school management.

Design/methodology/approach

The aim of this study is to determine how leadership by example, high communication leadership, human resource management and gender, influence two dimensions of teacher well-being, namely emotional and physical well-being. Gender was used as a moderating variable. The relationships between these variables are reflected in the hypotheses of this study. Linear regression analysis was used to test these hypotheses. The measurement scales were drawn from the literature. Data were obtained using non-probabilistic convenience sampling of 300 public and subsidized (concertado) high schools. To include large and medium-sized Spanish cities in the study, Madrid, Valencia, Malaga, and Murcia were selected. The final sample consisted of 315 high school teachers from 75 schools.

Findings

The results suggest that leadership by example and high communication leadership influence human resource management directly and positively. Human resource management, in turn, influences the physical and psychological well-being of schoolteachers.

Originality/value

This paper adds to the literature on leadership styles and human resource management by expanding the knowledge of factors influencing schoolteachers' well-being. To the best of the authors’ knowledge, this is the first article reporting a study on such factors in schools in Spain.
Effects of open climate on innovation radicality in SMEs: relevance of hidden innovation
Authors: Barba-Aragón María Isabel , Jimenez-Jimenez Daniel , Valle-Mestre Ledian
Published: June 2022

Purpose

Open innovation is an issue that has aroused great interest in recent years. The need to create an environment that facilitates the creation of ideas is essential for the implementation of a series of changes in organizational practices and routines that lead to the launch of new products. However, due to the more behavioral nature and the lesser externalization of these changes introduced in the company's internal processes, how this process occurs has not been studied in depth. The objective of this study is to analyze the effect of an open innovation climate on both incremental and radical product innovation. Moreover, it specifically analyzes the mediating role played by hidden innovation in this relationship.

Design/methodology/approach

The methodology used in this study was based on a survey of 213 Spanish SMEs, subsequently applying the structural equation methodology to contrast the results.

Findings

The results indicate that open innovation climate offers significant competitive advantages to SMEs. First, the open innovation climate in SMEs favorably influences product innovation (both incremental and radical). Secondly, it is observed that hidden innovations are essential to obtain product innovations. Finally, evidence of the mediating effect of hidden innovation has been obtained.

Research limitations/implications

Although the literature often focuses on visible innovation, materialized in product development, this study demonstrates the importance of other types of innovations that are necessary to launch new products. This is especially relevant for SMEs that, with limited resources, must be creative enough to involve their personnel in introducing changes that will lead to new products. This paper attempts to strengthen the previous literature on hidden innovation by contributing to the understanding of how SMEs improve their innovative processes. However, the study has the limitations derived from using a single informant to obtain data, using subjective-type scales and being a cross-sectional research.

Practical implications

Managers of SMEs involved in innovation processes should favor the creation of an open innovation climate and invest in organizational innovation. Governments should promote policies to support hidden and open innovation.

Originality/value

The main interest of this work is based on the importance of hidden innovation for the development of innovations. This study shows how organizations must make a series of organizational changes prior to the implementation of more visible innovations materialized in products. For this task, the creation of a favorable climate for the development of new ideas becomes a fundamental task. On the other hand, this study has focused on SMEs, which tend to have fewer means for the development of the right conditions for innovation and are often more neglected by scientific research.
Concerning the effect of radial thermal conductivity in a self-similar solution for rotating cone-disk systems
Authors: Shevchuk Igor V.
Published: June 2022

Purpose

Thus, the purposes of this study are to study the limits of applicability of the self-similar solution to the problem of fluid flow, heat and mass transfer in conical gaps with small conicity angles, to substantiate the impossibility of using a self-similar formulation of the problem in the case of large conicity angles and to substantiate the absence of the need to take into account the radial thermal conductivity in the energy equation in its self-similar formulation for the conicity angles up to 4°.

Design/methodology/approach

In the present work, an in-depth and extended analysis of the features of fluid flow and heat transfer in a conical gap at small angles of conicity up to 4° is performed. The Couette-type flow arising, in this case, was modeled using a self-similar formulation of the problem. A detailed analysis of fluid flow calculations using a self-similar system of equations showed that they provide the best agreement with experiments than other known approaches. It is confirmed that the self-similar system of flow and heat transfer equations is applicable only to small angles of conicity up to 4°, whereas, at large angles of conicity, this approach becomes unreasonable and leads to significantly inaccurate results. The heat transfer process in a conical gap with small angles of conicity can be modeled using the self-similar energy equation in the boundary layer approximation. It was shown that taking into account the radial thermal conductivity in the self-similar energy equation at small conicity angles up to 4° leads to maximum deviations of the Nusselt number up to 1.5% compared with the energy equation in the boundary layer approximation without taking into account the radial thermal conductivity.

Findings

It is confirmed that the self-similar system of fluid flow equations is applicable only for small conicity angles up to 4°. The inclusion of radial thermal conductivity in the model unnecessarily complicates the mathematical formulation of the problem and at small conicity angles up to 4° leads to insignificant deviations of the Nusselt number (maximum 1.5%). Heat transfer in a conical gap with small conicity angles up to 4° can be modeled using the self-similar energy equation in the boundary layer approximation.

Originality/value

This paper investigates the question of the validity of taking into account the radial heat conduction in the energy equation.
Factors affecting online learning, stress and anxiety during the COVID-19 pandemic in Saudi Arabia
Authors: Abdelwahed Nadia A. Abdelmegeed , Aldoghan Mohammed A. , Moustafa Mohamed A. , Soomro Bahadur Ali
Published: June 2022

Purpose

This study investigated the factors affecting online learning (OL) and stress and anxiety (SaA) during the COVID-19 pandemic in Saudi Arabia.

Design/methodology/approach

This study used a quantitative study and a survey questionnaire to collect the cross-sectional data. The authors sent 500 survey questionnaires to the respondents of which 262 samples were returned. This represented a 52% response rate. Finally, this study used 260 valid samples to derive this study’s findings.

Findings

Through structure equation modelling analysis, this study’s findings demonstrate that lack of time and support, technical problems and lack of technical skills negatively affect OL. In addition, this study’s findings show that cost and access to internet has a significant effect on OL. Finally, this study’s findings show that among Saudi Arabian university students OL is the significant predictor of SaA.

Practical implications

This study’s findings offer university authorities meaningful ways to identify replacements for the usage of harmful devices to lessen psychological problems during the COVID-19 pandemic. By pointing out students’ significant challenges and barriers during OL, this study’s findings support the smooth and parallel running of OL. Such challenges cause deprivation and frustration among the students. Therefore, to some extent, it may be a violation of their human rights. In this way, this study’s findings demonstrate how to overcome these violations.

Originality/value

By exploring the significant challenges faced by Saudi Arabian university students, this study’s findings offer an original and empirical contribution to the literature.
Cultural distance and post-acquisition performance: the role of absorptive capacity
Authors: Moura Stephanie Tonn Goulart , Falaster Christian , Silva-Rêgo Bernardo
Published: June 2022

Purpose

Cultural distance can be a challenge for internationalization. However, in some instances, it is possible that different cultures could represent a benefit for multinational enterprises (MNEs) from emerging contexts. Drawing on the knowledge-based view (KBV), the authors propose that greater cultural distances lead to benefits for multinationals seeking to absorb new knowledge overseas.

Design/methodology/approach

The authors performed ordinary least squares regressions with moderation tests over a database containing 101 cross-border acquisitions to test the study’s hypotheses. The acquisitions were performed by Brazilian firms between 1995 and 2015, targeting 24 host countries.

Findings

The study’s results indicate that cultural distance positively affects the firm's post-acquisition performance and that absorptive capacity moderates these results, improving the positive effect. The study suggests that cultural diversity is an asset for the multinationals in question.

Practical implications

When deciding to invest in a foreign country, managers should consider this cultural diversity as one more value creation driver, especially if the firm has well-developed innovation capabilities.

Originality/value

The study’s findings contribute to the international business literature providing further evidence that emerging markets multinationals can create value in acquisitions through the firm's abilities to exploit cultural asymmetries. Thus, the authors also emphasize that absorptive capacity plays a strategic role in multinational's international strategies.
Detection and quantification of Epstein–Barr virus, cytomegalovirus, and human herpesvirus‐6 in stomach frozen tissue of chronic gastritis and gastric cancer patients
Authors: Sarshari Behrang , Mohebbi Seyed Reza , Ravanshad Mehrdad , Shahrokh Shabnam , Aghdaei Hamid Asadzadeh , Zali Mohammad Reza
Published: June 2022

Human herpes viruses (HHVs) are among the most common infectious agents detected in the gastrointestinal tract that might be involved in oncogenesis and other gastrointestinal disorders. Although the link between the Epstein–Barr virus (EBV) and gastric cancer (GC) has been established, the role of the viruses in various stomach diseases remains unknown. The frequencies and viral copy number of EBV, cytomegalovirus (CMV), and human herpesvirus 6 (HHV‐6) among 50 gastric cancer tumors and 105 chronic gastritis tissues were measured by quantitative real‐time PCR. In the tumor specimens and the adjacent normal tissues EBV was found in 60% and 30.9%, CMV in 14% and 4.7%, and HHV‐6 in 18%, and 14.2%, respectively. The detection rate of EBV and CMV was found to be significantly higher in tumor tissues relative to the adjacent normal tissues. Also, in chronic gastritis, the frequency of EBV, CMV, and HHV‐6 was 19%, 12.3%, and 15.2%, respectively, compared with 16.4%, 1.1%, and 8.2% in their corresponding normal tissues. Here, the CMV frequency was found to be significantly higher in gastritis tissues relative to the adjacent normal tissues. Furthermore, viral load in both gastric cancer and gastritis groups was higher in either tumor or gastritis lesion compared with matched adjacent normal tissue. This study showed a clear association between gastric cancer with both EBV and CMV. Meanwhile, analyses revealed a strong association between the EBV, CMV, and HHV‐6 viral loads with gastritis (P = 0.0026, P < 0.0001, and P = 0.0405, respectively). Our results suggest that these three viruses might contribute to the induction and development the gastritis and gastric cancer.
Anti‐inflammatory effect a specific Lactiplantibacillus plantarum in an ovalbumin‐induced asthma model
Authors: Kishida Shigefumi , Kato‐Mori Yuko , Okamoto Minoru , Hagiwara Katsuro
Published: June 2022

Autoimmune, allergic, and respiratory inflammatory diseases are some of the most important health issues worldwide. Disorders of the gut microbiota have been associated with the induction of allergic and inflammatory diseases, and probiotics are being tested for disease prevention. We examined functional Lactiplantibacillus plantarum RGU (Lp‐1) to mice with ovalbumin (OVA)‐induced asthma model to elucidate the inhibitory effect on pathological progression in asthma model. Prior to the experiments, the intestinal lactic acid bacteria were reduced by administering multiple antibiotics (MAB) to evaluate the administration effect of lactic acid bacteria. Mice were administered with Lp‐1 or comparative control lactic acid bacteria in each group. After that, OVA‐induced asthma was induced, and cytokine gene expression and histological findings were compared. Exacerbation of lung lesions was confirmed in the MAB group. The Lp‐1 group mice had alleviated lung lesions with a decrease in IL‐1β, IL‐13, IL‐17 and an increase in IL‐10 of the splenocytes and bronchial lymph nodes compared with the MAB group, but not in the other groups. In OVA‐induced asthma, administration of specific Lactiplantibacillus was confirmed to induce anti‐inflammatory cytokines.
Acclimation in ants: Interference of communication and waterproofing through cuticular hydrocarbons in a multifunctional trait
Authors: Wittke Marti , Baumgart Lucas , Menzel Florian
Published: June 2022

Organismal traits may experience conflicting selection pressures if they fulfil different functions simultaneously. This can require trade‐offs between functions or alternatively functional separation between elements of the trait.

An important multifunctional trait in insects is the cuticular hydrocarbon (CHC) layer. CHCs cover the body of nearly all insects, protect against desiccation and serve as a communication signal. In social insects like ants, they provide cues for nestmate recognition. To maintain their waterproofing function, insects have to adjust CHC composition to current temperatures. These changes might affect information content and interfere with communication, which would be especially detrimental in social insects.

Here, we studied how acclimation affects nestmate recognition in two sister species of the ant genus Lasius. Colony fragments were exposed to three climate regimes. We analysed behaviour towards same and differently acclimated conspecifics, and determined which CHCs were related to acclimatory changes, colony differences and inter‐individual aggression.

Differential acclimation led to higher aggression and chemical distances among former nestmates. We identified small CHC subsets, which only differed among colonies or among acclimation treatments. Moreover, few compounds sufficed to explain inter‐individual aggression, suggesting that ants do not use the entire CHC profile for nestmate recognition and that colony identity is encoded in a redundant way.

Across individual CHCs, their contribution to colony differences and to differences among acclimatory treatments was negatively correlated, indicating that there is some degree of functional separation. However, CHC classes could not be clearly assigned to one or another function, indicating that the role of each CHC is idiosyncratic and may differ among species. Acclimatory effects and colony differences were more independent from each other in L. platythorax than in L. niger, indicating that functional separation can differ even among sister species.

Our results show that CHC functions are more intertwined than previously assumed, suggesting that insects cannot optimise all functions independently. The main constraint might be the need to maintain a certain phase behaviour of the CHC layer, which depends on CHC composition and affects functionality. The need to separate functions might depend on species‐specific ecological and life‐history parameters.

Read the free Plain Language Summary for this article on the Journal blog.
Manipulating actions: A selective two‐option device for cognitive experiments in wild animals
Authors: Wild Sonja , Alarcón‐Nieto Gustavo , Chimento Michael , Aplin Lucy M.
Published: June 2022

Advances in biologging technologies have significantly improved our ability to track individual animals' behaviour in their natural environment. Beyond observations, automation of data collection has revolutionized cognitive experiments in the wild. For example, radio‐frequency identification (RFID) antennae embedded in ‘puzzle box’ devices have allowed for large‐scale cognitive experiments where individuals tagged with passive integrated transponder (PIT) tags interact with puzzle boxes to gain a food reward, with devices logging both the identity and solving action of visitors.

Here, we extended the scope of wild cognitive experiments by developing a fully automated selective two‐option foraging device to specifically control which actions lead to a food reward and which remain unrewarded. Selective devices were based on a sliding‐door foraging puzzle, and built using commercially available low‐cost electronics.

We tested it on two free‐ranging PIT‐tagged subpopulations of great tits Parus major as a proof of concept. We conducted a diffusion experiment where birds learned from trained demonstrators to get a food reward by sliding the door either to the left or right. We then restricted access of knowledgeable birds to their less preferred side and calculated the latency until birds produced solutions as a measure of behavioural flexibility.

A total of 22 of 23 knowledgeable birds produced at least one solution on their less preferred side after being restricted, with higher‐frequency solvers being faster at doing so. In addition, 18 of the 23 birds reached their solving rate from prior to the restriction on their less preferred side, with birds with stronger prior side preference taking longer to do so.

We therefore introduce and successfully test a new selective two‐option puzzle box, providing detailed instructions and freely available software that allows reproducibility. It extends the functionality of existing systems by allowing fine‐scale manipulations of individuals' actions and opens a large range of possibilities to study cognitive processes in wild animal populations.
Blockage of PD‐L1 by FERMT3‐mediated Wnt/β‐catenin signalling regulates chemoresistance and immune evasion of colorectal cancer cells
Authors: Tang Yanhua , Nan Nan , Gui Chuanzhi , Zhou Xuan , Jiang Wenyong , Zhou Xiaoqian
Published: June 2022

Colorectal cancer (CRC) constitutes a major public health problem because of the high rate of morbidity and mortality. Chemotherapy and immunotherapy are the major and promising strategies for cancer patients including CRC; nevertheless, chemoresistance and immune escape limit the final efficacy of the above approaches. FERMT3 has proven to exert a critical role in the immune system and has contradictive effects on cancer progression. In this study, bioinformatics database analysis and clinical specimen detection both corroborated the downregulation of FERMT3 in CRC tissues and cells. Of interest, overexpression of FERMT3 suppressed CRC cell invasion and sensitized cells to 5‐fluorouracil (5‐FU) by reducing cell viability and increasing cell apoptosis and caspase 3 activity. Noticeably, FERMT3 upregulation enhanced natural killer (NK) cells activation by increasing secretions of interferon γ (IFN‐γ) and tumour necrosis factor α (TNF‐α) when NK cells were co‐cultured with CRC cells. Importantly, upregulation of FERMT3 promoted NK cell‐mediated killing of CRC cells. Mechanically, FERMT3 inhibited the aberrant activation of Wnt/β‐catenin signalling and the subsequent programmed death‐ligand 1 (PD‐L1) expression in CRC cells. Moreover, knockdown of PD‐L1 suppressed CRC cell invasion, 5‐FU resistance and NK cells‐mediated tumour killing. Additionally, reactivating the Wnt/β‐catenin signalling with a specific WNT agonist CAS 853220–52‐7 overturned the efficacy of FERMT3 overexpression against CRC cell invasion, 5‐FU chemoresistance and cell susceptibility to NK cell‐mediated cytotoxicity. Therefore, the current findings substantiate that FERMT3 elevation may attenuate CRC cell chemoresistance and NK cell‐mediated immune response to tumour cells by inhibiting Wnt/β‐catenin‐PD‐L1 signalling. Therefore, FERMT3 elevation may be a promising therapeutic approach to overcome chemoresistance and immune evasion in CRC.
Growth of nitrite‐oxidizing Nitrospira and ammonia‐oxidizing Nitrosomonas in marine recirculating trickling biofilter reactors
Authors: Oshiki Mamoru , Netsu Hirotoshi , Kuroda Kyohei , Narihiro Takashi , Fujii Naoki , Kindaichi Tomonori , Suzuki Yoshiyuki , Watari Takahiro , Hatamoto Masashi , Yamaguchi Takashi , Araki Nobuo , Okabe Satoshi
Published: June 2022

Aerobic ammonia and nitrite oxidation reactions are fundamental biogeochemical reactions contributing to the global nitrogen cycle. Although aerobic nitrite oxidation yields 4.8‐folds less Gibbs free energy (∆Gr) than aerobic ammonia oxidation in the NH4+‐feeding marine recirculating trickling biofilter reactors operated in the present study, nitrite‐oxidizing and not ammonia‐oxidizing Nitrospira (sublineage IV) outnumbered ammonia‐oxidizing Nitrosomonas (relative abundance; 53.8% and 7.59% respectively). CO2 assimilation efficiencies during ammonia or nitrite oxidation were 0.077 μmol‐14CO2/μmol‐NH3 and 0.053–0.054 μmol‐14CO2/μmol‐NO2− respectively, and the difference between ammonia and nitrite oxidation was much smaller than the difference of ∆Gr. Free‐energy efficiency of nitrite oxidation was higher than ammonia oxidation (31%–32% and 13% respectively), and high CO2 assimilation and free‐energy efficiencies were a determinant for the dominance of Nitrospira over Nitrosomonas. Washout of Nitrospira and Nitrosomonas from the trickling biofilter reactors was also examined by quantitative PCR assay. Normalized copy numbers of Nitrosomonas amoA were 1.5‐ to 1.7‐folds greater than Nitrospira nxrB and 16S rRNA gene in the reactor effluents. Nitrosomonas was more susceptible for washout than Nitrospira in the trickling biofilter reactors, which was another determinant for the dominance of Nitrospira in the trickling biofilter reactors.
To telework or not to telework: Does the macro context matter? A signalling theory analysis of employee interpretations of telework in times of turbulence
Authors: Cañibano Almudena , Avgoustaki Argyro
Published: June 2022

How do workers make sense of telework and respond to it in turbulent times? This study of a consultancy firm in Spain, during the 2008 financial crisis, explores employee interpretations of telework in the context of major macro‐economic disruption. We draw on signalling theory to consider telework as a signal sent by the organisation and argue that the environment in which the signal occurs changes employees' interpretations. While telework is generally understood as an employee‐centred practice, we find that in an economic crisis it is also interpreted as a potential threat for employees. Therefore, the meaning of telework is not predetermined, but continually shaped socially considering events beyond the boundaries of the firm. We propose adopting a social constructivist view to consider human resource (HR) practices as objects experienced and interpreted within their wider social contexts. We shed new light on signalling theory and HR studies by offering insights on the relevance of the signalling environment for interpreting messages, and bring forth the concept of “external fit”.
Selenium‐enriched peptides isolated from Cardamine violifolia are potent in suppressing proliferation and enhancing apoptosis of HepG2 cells
Authors: Lin Yue , Li Yue , Cong Xin , Xia Yongmei , Huang Dejian , Chen Shangwei , Zhu Song
Published: June 2022

Selenium (Se)‐enriched peptides were isolated from Cardamine violifolia by enzymatic hydrolysis and ultrafiltration. S3 (molecular weight [MW] distribution of 3–5 kDa) exhibited the strongest inhibitory effect on HepG2 cells and was thus screened using the 3‐(4,5‐dimethylthiazole‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay; it was found to have a high organic Se content. Its amino acid sequence was determined using HPLC‐MS/MS. We then examined its ability to inhibit tumor cell proliferation and found that it arrested tumor cells in the S phase; moreover, it could induce cancer cell apoptosis. Following S3 treatment, we observed a decrease in mitochondrial membrane potential and an increase in cell calcium content. Upon S3 treatment at 60 µg/ml, the relative activities of caspase‐3 and caspase‐9 increased by 1.48 times and 2.17 times, and the contents of PI3K and AKT decreased from 2.05 ng/L and 1.95 ng/L to 0.71 ng/L and 0.50 ng/L, respectively, when compared with the control group. Transcriptomic analysis revealed significant changes in the PI3K–AKT pathway following S3 treatment. This study thus established a foundation for additional development of Se‐enriched peptides from C. violifolia as a functional food.

Practical Application

Cardamine violifolia is a Se‐tolerant cruciferous plant that can metabolically transform inorganic Se into organic Se that exists in the form of a selenoprotein. Se‐enriched peptide obtained by extraction and enzymolysis of selenoprotein, as an organic combination of organic Se and peptide, possess valuable biological activities. In this paper, the effect of Se‐enriched peptides of C. violifolia on tumor cells was studied via cell experiments, and its mechanism was preliminarily discussed, which should provide a theoretical basis for developing functional foods containing C. violifolia.
Lithium use during breastfeeding was safe in healthy full‐term infants under strict monitoring
Authors: Heinonen Essi , Tötterman Katarina , Bäck Karin , Sarman Ihsan , Svedenkrans Jenny , Forsberg Lisa
Published: June 2022

Aim

Previous studies on breastfeeding during lithium therapy have shown conflicting results. The aim of this study was to evaluate the safety when practising thorough follow‐up of the infants.

Method

This retrospective study focused on women with lithium medication, and their breastfed infants born between 2006 and 2021 in Stockholm, Sweden. Information about infant serum lithium concentrations and clinical status was collected from medical records.

Results

In total, 30 infants exposed to lithium through breastmilk, 21 girls and 9 boys, were included. The median age at follow‐up was 40 days (range 8–364 days). The median lithium serum concentration was 0.10 mmol/L in the second week of life (range <0.05–0.7 mmol/L), 0.08 in week 2–4 (range <0.05–1.2), 0.06 in the second month of life (range <0.05–0.2) and 0.07 after 2 months of age (range <0.05–0.2). Unexpectedly high lithium concentrations were found in two infants in the first month of life. Apart from poor weight gain, no adverse effects were found.

Conclusion

Serum lithium concentrations in breastfed infants were stabilised at barely measurable levels after the first weeks of life. Before that, concentrations higher than the mothers were found. Lithium treatment during breastfeeding can be considered safe under strict follow‐up.
Empagliflozin modulates CD4+ T‐cell differentiation via metabolic reprogramming in immune thrombocytopenia
Authors: Qin Jing , Liu Qiang , Liu Anli , Leng Shaoqiu , Wang Shuwen , Li Chaoyang , Ma Ji , Peng Jun , Xu Miao
Published: June 2022

Immune thrombocytopenia (ITP) is an acquired autoimmune disease, in which the imbalance of CD4+ T cell subsets play a key role in the pathogenesis. Since T cells highly depend on metabolism for their function, we hypothesized that T cell dysfunction may be due to intracellular metabolic reprogramming. We found that in ITP, T cell metabolism shifts from oxidative phosphorylation to glycolysis. Empagliflozin, a sodium–glucose cotransporter 2 inhibitor, has shown regulatory metabolic effects on proximal tubular epithelial cells and cardiac cells beyond glucose lowering. However, the effects of empagliflozin on T cells remain unknown. To further investigate the metabolic dysfunction of CD4+ T cells in ITP, we explored the effect of empagliflozin on CD4+ T‐cell differentiation in ITP. Our results are the first to show that increased glycolysis in CD4+ T cells resulted in an unbalanced CD4+ T‐cell population. Furthermore, empagliflozin can affect the differentiation of CD4+ T‐cell subsets by inhibiting Th1 and Th17 cell populations while increasing Tregs. Empagliflozin appears to regulate CD4+ T cells through inhibiting the mTOR signal pathway. Considering these results, we propose that empagliflozin could be used as a potential therapeutic option for ITP by modulating metabolic reprogramming in CD4+ T cells.
Iterated expectations under rank‐dependent expected utility and implications for common valuation methods
Authors: Stomper Alex , Vierø Marie‐Louise
Published: June 2022

This paper investigates the applicability of common valuation techniques in finance when the decision‐maker's preferences can be described by the rank‐dependent expected utility model. Under expected utility theory, compound lotteries can be valued by “iterating” expectations: the expected utility of a compound lottery is the expected value of a simple lottery over prizes that are certainty equivalents to follow‐up lotteries. We derive necessary and sufficient conditions for a similar valuation technique in the framework of rank‐dependent expected utility when a consequentialist decision‐maker has to choose between prospects that belong to a comonotonic class. The conditions coincide with those for dynamically consistent behaviour of such a decision‐maker. The decision‐maker must update her preferences based on a benchmark prospect that can be interpreted as a formalization of “black‐and‐white thinking.”
Greasing (small) palms: Early rejection of bribery
Authors: Reyes‐Jaquez Bolivar , Koenig Melissa A.
Published: June 2022

We tested when U.S. children reject bribery, and whether their rejections vary by public versus private setting. Six‐ to 10‐year‐olds (224 children, 118 boys, 106 girls, majority‐White) participated across four experiments, in which participants indicated whether a contest judge should accept a contestant's financial gift. Children conveyed their preferences while in public or in private (in the presence or absence of an adult experimenter). Children's rejections of bribes were found to increase with age. Notably, younger children's acceptance rate was higher when the experimenter was present than in their absence; in contrast, older children showed comparable rejection rates across settings. Limitations in children's early reasoning about bribery, including the reputational and moral implications of accepting bribes in public, are discussed.
PRAME immunohistochemistry for melanoma diagnosis: A STARD‐compliant diagnostic accuracy study
Authors: O'Connor Michaela K. , Dai Hongyan , Fraga Garth R.
Published: June 2022

Background

Preferentially expressed antigen in melanoma (PRAME) is a tumor‐associated antigen that is frequently expressed in cutaneous melanoma and can be evaluated by immunohistochemistry. Earlier studies on PRAME utilized case‐control study designs that may misestimate diagnostic accuracy and lack generalizability.

Methods

Using retrospective cohort selection, a cross‐sectional study of diagnostic accuracy of PRAME was conducted according to standards for reporting diagnostic accuracy studies requirements.

Results

Mean PRAME positive fraction was higher in 42 malignant melanocytic lesions than 101 benign melanocytic lesions (0.71 ± 0.30 vs. 0.13 ± 0.20, p < 0.01). Receiver operating characteristic curve showed the test was effective (area under the curve = 0.90). Global PRAME 4+ scores (>75%) were associated with sensitivity of 0.63, specificity of 0.97, accuracy of 0.87, and excellent interrater concordance (Kappa = 0.83). Lower cutoffs for PRAME of 2+ (>25%) and 3+ (>50%) produced higher joint sensitivity/specificity (Youden index) than PRAME 4+, but lower accuracy.

Conclusion

PRAME as it is used in clinical practice is an effective test for melanoma. PRAME is best used as an ordinal variable to calculate the posttest probability of melanoma. PRAME ≤25% (0/1+) favors nevus, PRAME 26%–75% (2/3+) is noncontributory, and PRAME >75% (4+) favors melanoma.