bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurometabolic timecourse of healthy aging
Authors: Gong Tao , Hui Steve C.N. , Zöllner Helge J. , Britton Mark , Song Yulu , Chen Yufan , Gudmundson Aaron T. , Hupfeld Kathleen E. , Murali-Manohar Saipavitra , Porges Eric C. , Oeltzschner Georg , Chen Weibo , Wang Guangbin , Edden Richard A. E.
Published: June 2022

Purpose

The neurometabolic timecourse of healthy aging is not well-established, in part due to diversity of quantification methodology. In this study, a large structured cross-sectional cohort of male and female subjects throughout adulthood was recruited to investigate neurometabolic changes as a function of age, using consensus-recommended magnetic resonance spectroscopy quantification methods.

Methods

102 healthy volunteers, with approximately equal numbers of male and female participants in each decade of age from the 20s, 30s, 40s, 50s, and 60s, were recruited with IRB approval. MR spectroscopic data were acquired on a 3T MRI scanner. Metabolite spectra were acquired using PRESS localization (TE = 30 ms; 96 transients) in the centrum semiovale (CSO) and posterior cingulate cortex (PCC). Water-suppressed spectra were modeled using the Osprey algorithm, employing a basis set of 18 simulated metabolite basis functions and a cohort-mean measured macromolecular spectrum. Pearson correlations were conducted to assess relationships between metabolite concentrations and age for each voxel; paired t-tests were run to determine whether metabolite concentrations differed between the PCC and CSO.

Results

Two datasets were excluded (1 ethanol; 1 unacceptably large lipid signal). Statistically significant age-by-metabolite correlations were seen for tCr (R2=0.36; p<0.001), tCho (R2=0.11; p<0.001), sI (R2=0.11; p=0.004), and mI (R2=0.10; p<0.001) in the CSO, and tCr (R2=0.15; p<0.001), tCho (R2=0.11; p<0.001), and GABA (R2=0.11; p=0.003) in the PCC. No significant correlations were seen between tNAA, NAA, GSH, Glx or Glu and age in either region (all p>0.25). Levels of sI were significantly higher in the PCC in female subjects (p<0.001) than in male subjects. There was a significant positive correlation between linewidth and age.

Conclusion

The results indicated age correlations for tCho, tCr, sI, and mI in CSO and for tCr, tCho and GABA in PCC, while no age-related changes were found for NAA, tNAA, GSH, Glu or Glx. Our results provide a normative foundation for future work investigating the neurometabolic time course of healthy aging using MRS.

Highlights

A large structured cross-sectional cohort of neurometabolic aging dataset is presented;

Age correlations were observed for tCho, tCr, sI, and mI in CSO and for tCr, tCho and GABA in PCC;

No age correlations were found for NAA, tNAA, GSH, Glu or Glx in either region.
Better together against genetic effect heterogeneity: a sex-combined interaction analysis of testosterone levels in the UK Biobank data
Authors: Lin Boxi , Sun Lei
Published: June 2022

The effect of a genetic variant on a complex trait may differ between female and male, and in the presence of such genetic effect heterogeneity, sex-stratified analysis is often used. For example, genetic effects are sex-specific for testosterone levels, and sex-stratified analysis of testosterone in literature provided easy-to-interpret, sex-specific effect size estimates. However, from the perspective of association testing power, sex-stratified analysis may not be the best approach. As sex-specific genetic effect implies SNP×Sex interaction effect, jointly testing SNP main and SNP×Sex interaction effects may be more powerful than sex-stratified analysis or the standard main-effect testing approach. Moreover, since individual data may be unavailable, it is then of interest to study if the interaction analysis can be derived from sex-stratified summary statistics. We considered several different sex-combined methods and evaluated them through extensive simulation studies. We observed that a) the joint SNP main and SNP×Sex interaction analysis is most robust to a wide range of genetic models, and b) this joint interaction testing result can be obtained by quadratically combining sex-stratified summary statistics (i.e. squared sum of the sex-stratified summary statistics). We then reanalysed the testosterone levels of the UK Biobank data using sex-combined interaction analysis, which identified 27 new loci that were missed by the sex-stratified approach and the standard sex-combined analysis. Finally, we provide supporting association evidence for nine new loci, uniquely identified by the sex-combined interaction analysis, from earlier association studies of either testosterone level or steroid biosynthesis pathway where testosterone is synthesized. We thus recommend sex-combined interaction analysis, particularly for traits with known sex differences, for most powerful association testing, then followed by sex-stratified analysis for effect size estimation and interpretation.
Endogenous GDF15 and FGF21 additively alleviate hepatic steatosis and insulin resistance in obese mice
Authors: Patel Satish , Haider Afreen , Alvarez-Guaita Anna , Bidault Guillaume , El-sayed Moustafa Julia Sarah , Guiu-Jurado Esther , Tadross John A. , Warner James , Harrison James , Virtue Samuel , Scurria Fabio , Zvetkova Ilona , Blüher Matthias , Small Kerrin S. , O’Rahilly Stephen , Savage David B.
Published: June 2022

Obesity in mice and humans is associated with elevated levels of at least two hormones responsive to cellular stress, namely GDF15 and FGF21. Over-expression of each of these is associated with weight loss and beneficial metabolic changes but where they are secreted from and what they are required for physiologically in the context of overfeeding remains unclear. Here we used tissue selective knockout mouse models to establish that, like FGF21, circulating GDF15 is primarily derived from the liver, rather than adipose tissue, muscle or macrophages in high fat fed mice. Combined whole body deletion of FGF21 and GDF15 does not result in any additional weight gain in high fat fed mice but is associated with significantly greater hepatic steatosis and insulin resistance. Collectively the data suggest that activation of the integrated stress response in hepatocytes is a major driver for GDF15 and FGF21 secretion in the context of overfeeding, and that they both act to alleviate this metabolic stress.
Integrating inflammatory biomarker analysis and artificial intelligence-enabled image-based profiling to identify drug targets for intestinal fibrosis
Authors: Yu Shan , Kalinin Alexandr A. , Paraskevopoulou Maria D. , Maruggi Marco , Cheng Jie , Tang Jie , Icke Ilknur , Luo Yi , Wei Qun , Scheibe Dan , Hunter Joel , Singh Shantanu , Nguyen Deborah , Carpenter Anne E. , Horman Shane R.
Published: June 2022

Intestinal fibrosis is a common complication of several enteropathies with inflammatory bowel disease being the major cause. The progression of intestinal fibrosis may lead to intestinal stenosis and obstruction. Even with an increased understanding of tissue fibrogenesis, there are no approved treatments for intestinal fibrosis. Historically, drug discovery for diseases like intestinal fibrosis has been impeded by a lack of screenable cellular phenotypes. Here we applied Cell Painting, a scalable image-based morphology assay, augmented with machine learning algorithms to identify small molecules that were able to morphologically reverse the activated fibrotic phenotype of intestinal myofibroblasts under pro-fibrotic TNFα stimulus. In combination with measuring CXCL10, a common pro-inflammatory cytokine in intestinal fibrosis, we carried out a high-throughput small molecule chemogenomics screen of approximately 5000 compounds with known targets or mechanisms, which have achieved clinical stage or approval by the FDA. Through the use of two divergent analytical methods, we identified several compounds and target classes that are potentially able to treat intestinal fibrosis. The phenotypic screening platform described here represents significant improvements in identifying a wide range of drug targets over conventional methods by integrating morphological analyses and artificial intelligence using pathologically-relevant cells and disease-relevant stimuli.
Variation in morpho-physiological and metabolic responses to low nitrogen stress across the sorghum association panel
Authors: Grzybowski Marcin W. , Zwiener Mackenzie , Jin Hongyu , Wijewardane Nuwan K. , Atefi Abbas , Naldrett Michael J. , Alvarez Sophie , Ge Yufeng , Schnable James C.
Published: June 2022

Access to biologically available nitrogen is a key constraint on plant growth in both natural and agricultural settings. Variation in tolerance to nitrogen deficit stress and productivity in nitrogen limited conditions exists both within and between plant species. Here we quantified variation in the metabolic, physiological, and morphological responses of a sorghum association panel assembled to represent global genetic diversity to long term, moderate, nitrogen deficit stress and the relationship of these responses to grain yield under both conditions. Grain yield exhibits substantial genotype by environment interaction while many other morphological and physiological traits exhibited consistent responses to nitrogen stress across the population. Large scale nontargeted metabolic profiling for a subset of lines in both conditions identified a range of metabolic responses to long term nitrogen deficit stress as well as several metabolites associated with variation in the degree of yield plasticity specific sorghum genotypes exhibited in response to nitrogen deficit stress.
Genome-wide prediction of pathogenic gain- and loss-of-function variants from ensemble learning of a diverse feature set
Authors: Stein David , Sevim Bayrak Çiğdem , Wu Yiming , Kars Meltem Ece , Stenson Peter D. , Cooper David N. , Schlessinger Avner , Itan Yuval
Published: June 2022

Gain-of-function (GOF) variants give rise to increased or novel protein functions whereas loss-of-function (LOF) variants lead to diminished protein function. GOF and LOF variants can result in markedly varying phenotypes, even when occurring in the same gene. However, experimental approaches for identifying GOF and LOF are generally slow and costly, whilst currently available computational methods have not been optimized to discriminate between GOF and LOF variants. We have developed LoGoFunc, an ensemble machine learning method for predicting pathogenic GOF, pathogenic LOF, and neutral genetic variants. LoGoFunc was trained on a broad range of gene-, protein-, and variant-level features describing diverse biological characteristics, as well as network features summarizing the protein-protein interactome and structural features calculated from AlphaFold2 protein models. We analyzed GOF, LOF, and neutral variants in terms of local protein structure and function, splicing disruption, and phenotypic associations, thereby revealing previously unreported relationships between various biological phenomena and variant functional outcomes. For example, GOF and LOF variants exhibit contrasting enrichments in protein structural and functional regions, whilst LOF variants are more likely to disrupt canonical splicing as indicated by splicing-related features employed by the model. Further, by performing phenome-wide association studies (PheWAS), we identified strong associations between relevant phenotypes and high-confidence predicted GOF and LOF variants. LoGoFunc outperforms other tools trained solely to predict pathogenicity or general variant impact for the identification of pathogenic GOF and LOF variants.
Updating contextual sensory expectations for adaptive behaviour
Authors: Ferrari Ambra , Richter David , de Lange Floris P.
Published: June 2022

The brain has the extraordinary capacity to construct predictive models of the environment by internalizing statistical regularities in the sensory inputs. The resulting sensory expectations shape how we perceive and react to the world; at the neural level, this relates to decreased neural responses to expected than unexpected stimuli (‘expectation suppression’). Crucially, expectations may need revision as context changes. However, existing research has often neglected this issue. Further, it is unclear whether contextual revisions apply selectively to expectations relevant to the task at hand, hence serving adaptive behaviour. The present fMRI study examined how contextual visual expectations spread throughout the cortical hierarchy as participants update their beliefs. We created a volatile environment with two state spaces presented over separate contexts and controlled by an independent contextualizing signal. Participants attended a training session before scanning to learn contextual temporal associations among pairs of object images. The fMRI experiment then tested for the emergence of contextual expectation suppression in two separate tasks, respectively with task-relevant and task-irrelevant expectations. Behavioural and neural effects of contextual expectation emerged progressively across the cortical hierarchy as participants attuned themselves to the context: expectation suppression appeared first in the insula, inferior frontal gyrus and posterior parietal cortex, followed by the ventral visual stream, up to early visual cortex. This applied selectively to task-relevant expectations. Taken together, the present results suggest that an insular and frontoparietal executive control network may guide the flexible deployment of contextual sensory expectations for adaptive behaviour in our complex and dynamic world.

Significance statement

The world is structured by statistical regularities, which we use to predict the future. This is often accompanied by suppressed neural responses to expected compared with unexpected events (‘expectation suppression’). Crucially, the world is also highly volatile and context-dependent: expected events may become unexpected when the context changes, thus raising the crucial need for belief updating. However, this issue has generally been neglected. By setting up a volatile environment, we show that expectation suppression emerges first in executive control regions, followed by relevant sensory areas, only when observers use their expectations to optimise behaviour. This provides surprising yet clear evidence on how the brain controls the updating of sensory expectations for adaptive behaviour in our ever-changing world.
The trifecta of disease avoidance, silique shattering resistance and flowering period elongation achieved by theBnaIDAediting inBrassica napus
Authors: Geng Rui , Shan Yue , Li Lei , Shi Chun-Lin , Wang Jin , Zhang Wei , Sarwar Rehman , Xue Yi-Xuan , Li Yu-Long , Zhu Ke-Ming , Wang Zheng , Xu Li-Zhang , Aalen Reidunn B. , Tan Xiao-Li
Published: June 2022

Rapeseed (Brassica napus) oil is a main vegetable oil source in the world. The devastating disease of stem rot caused by the necrotrophic fungusSclerotinia sclerotiorumand pod shattering led to a great yield loss inBrassica napus. S.sclerotioruminfects the rapeseed by the detached floral petals, in which the released ascospores land and germinate as mycelium, then the petals fall on the leaves at lower part of the rapeseed and heavily attacks the leaves and stems. The prevention of petal-shedding is a promising approach to avoid the stem rot damage, moreover, longer period of flowering time will bring rapeseed flower tourism a huge economic benefit. Notably, IDA (INFLORESCENCE DEFICIENT IN ABSCISSION) and IDA-LIKE(IDL) protein control floral organ abscission inArabidopsis thaliana. In our study, the precisely editing of two IDA homologues genes using CRISPR/Cas9 system inBrassica napuscaused the petal attaching to the flower till pod mature and enhancing the silique dehiscence resistance. Incubating theS.sclerotiorumto petal showed the edited rapeseed avoiding the infection ofS.sclerotiorumRNA-Seq analysis demonstrated that in the editted plant, the genes involed in IDA pathway were regulated, while other genes keep unaltered. Investigation of agronomic traits showed that no positive the agronimic traits was introduced in editted plant. Our study demonstrated that mutation of two BnaIDAs creating a promising germplasm for disease avoidance, siliques shattering resistance and flowering period elongation which will contribute great to rapeseed industry.
Extracurricular roles and divergent regulation of FAMA in Brachypodium and Arabidopsis stomatal development
Authors: McKown Katelyn H. , Anleu Gil M. Ximena , Mair Andrea , Xu Shouling , Bergmann Dominique C.
Published: June 2022

Stomata, cellular valves found on the surface of aerial plant tissues, present a paradigm for studying cell fate and patterning in plants. A highly conserved core set of related basic helix-loop-helix (bHLH) transcription factors (TFs) regulate aspects of stomatal cell identity in diverse species. We characterized BdFAMA in the temperate grass, Brachypodium distachyon, and found this late-acting TF was necessary and sufficient for specifying stomatal GC fate, and unexpectedly could also induce the recruitment of subsidiary cells in the absence of its paralogue, BdMUTE. The overlap in function is paralleled by an overlap in expression pattern and by unique regulatory relationships between BdMUTE and BdFAMA. To better appreciate the relationships among the Brachypodium stomatal bHLHs, we characterized the diversity of bHLH complexes through in vivo proteomics in developing leaves and found evidence for multiple shared interaction partners. The ability of BdFAMA to compensate for BdMUTE then prompted us to reexamine the roles of these paralogues in Arabidopsis. By testing genetic sufficiency within and across species, we found that, while BdFAMA and AtFAMA can rescue stomatal production in Arabidopsis fama and mute mutants, only AtFAMA can participate in the specification of Brassica-family-specific myrosin idioblasts. Taken together, our findings further our understanding of how the molecular framework of stomatal development has been reprogrammed across the monocot/dicot divide, as well as within the grasses, to produce distinct stomatal forms and patterns, and compel us to refine the current models of stomatal bHLH function and regulatory feedbacks amongst paralogues.
Sphingosine-1-phosphate regulates Plasmodium histone deacetylase activity and exhibits epigenetic control over cell death and differentiation
Authors: Sah Raj Kumar , Anand Sakshi , Kumari Geeta , Saini Monika , Hada Rahul Singh , Madan Evanka , Gupta Aashima , Singh Shailja
Published: June 2022

Histone deacetylases (HDACs) play a key role in cellular processes by the regulation of gene transcription. This study contributes a novel insight how Plasmodium falciparum HDAC (PfHDAC-1) is regulated by S1P produced by host erythrocyte SphK-1. The binding of S1P with endogenous nuclear extract PfHDAC-1 and recombinant PfHDAC-1 blocks their activity. A significant modulation in transcriptional regulation of P. falciparum HDAC regulated genes resulted upon inhibition of S1P production through blocking of hSphK-1 by clinical SphK-1 inhibitor PF-543. PF-543 led to profound decrease in S1P in the parasite’s nuclear fraction. The significant modulation of PfHDAC-1 regulated specific candidate genes related to gametocytogenesis, virulence and proliferation was observed in parasite treated with SphK-1 inhibitor, suggesting S1P targets PfHDAC-1 and participates in epigenetic regulation of these key cellular processes. The epigenetic modulation of parasite cell growth and differentiation by host provides a novel approach for the developmenthost-targeted therapeutics.
Genomic analysis unveils the role of genome degradation events and gene flux in the emergence and persistence ofS. Paratyphi A lineages
Authors: Jacob Jobin John , Pragasam Agila K , Vasudevan Karthick , V Aravind , T Monisha Priya , T Tharani Priya , Ray Pallab , Gupta Madhu , Kapil Arti , Bai Sulochana Putil , Nagaraj Savitha , Saigal Karnika , Chandola Temsunaro Rongsen , Thomas Maria , Bavdekar Ashish , Ebenezer Sheena Evelyn , Shastri Jayanthi , De Anuradha , Dutta Shantha , Alexander Anna P , Koshy Roshine Mary , Jinka Dasaratha R , Singh Ashita , Srivastava Sunil Kumar , Anandan Shalini , Dougan Gordon , John Jacob , Kang Gagandeep , Veeraraghavan Balaji , Mutreja Ankur
Published: June 2022

Paratyphoid fever caused byS. Paratyphi A is endemic in parts of Asia and Sub-Saharan Africa. The proportion of enteric fever cases caused byS. Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory ofS. Paratyphi A isolates collected as part of the Indian enteric fever surveillance study “Surveillance of Enteric Fever in India (SEFI).” In the study period (2017-2020),S. Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the globalS. Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis documented that the genome degradation events and gene acquisitions or losses play a major role in the evolution of newS. Paratyphi A lineages/sub-lineages. A total of 10 pseudogene-forming mutations possibly associated with the emergence of lineages were identified. Pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3.2/2.3.3 and 1.2.2 genotypes, respectively. We also identified that the six characteristic missense mutations associated with the lipopolysaccharide (LPS) biosynthesis genes ofS. Paratyphi A confer only a low structural impact and would therefore have minimal impact on vaccine effectiveness. SinceS. Paratyphi A is human restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and intervention by means of genomic surveillance would be continually needed to avoidS. Paratyphi A serovar becoming a public health threat similar to theS. Typhi of today.
Peroxiredoxin 5 regulates osteogenic differentiation via interaction with hnRNPK during bone regeneration
Authors: Cho Eunjin , Che Xiangguo , Ang Mary Jasmin , Cheon Seongmin , Lee Jinkyung , Kim Kwang Soo , Lee Chang Hoon , Lee Sang-Yeop , Yang Hee-Young , Moon Changjong , Park Chungoo , Choi Je-Yong , Lee Tae-Hoon
Published: June 2022

Peroxiredoxin 5 (Prdx5) is involved in pathophysiological regulation via the stress-induced cellular response. However, the function of Prdx5 in the bone remains largely unknown. Here, we show that Prdx5 is involved in osteoclast and osteoblast differentiation, resulting in osteoporotic phenotypes inPrdx5knockout (Prdx5Ko) mice. Through immunoprecipitation and liquid chromatography combined with tandem mass spectrometry analysis, heterogeneous nuclear ribonucleoprotein K (hnRNPK) was identified as a potential binding partner of Prdx5 during osteoblast differentiationin vitro. We found that Prdx5 acts as a negative regulator of hnRNPK-mediated osteocalcin (Ocn) expression. In addition, transcriptomic analysis revealed thatin vitrodifferentiated osteoclasts from the bone marrow-derived macrophages ofPrdx5Komice showed enhanced expression of several osteoclast-related genes. These findings indicate that Prdx5 might contribute to the maintenance of bone homeostasis by regulating osteoblast differentiation. This study proposes a new function of Prdx5 in bone remodeling that may be used in developing therapeutic strategies for bone diseases.
Multiplex CRISPR strategy targeting viral genome for agriculture and clinical use
Authors: Zheng Zezhong , Xu Lei , Dou Hongwei , Zhou Yixuan , Feng Xu , He Xiangjun , Tian Zhen , Song Lingling , Gao Yangbin , Mo Guolong , Hu Jiapan , Zhao Hongye , Wei Hongjiang , Church George M. , Yang Luhan
Published: June 2022

African Swine Fever (ASF) is a viral disease with exceptionally high lethality in domestic pigs and wild boar worldwide1, 2, without any effective vaccine or drug to prevent its spread. In this study, we established a multiplexable CRISPR-Cas-gRNA system targeting 13 genomic loci in the ASF virus genome that could prevent viral replication by cutting its genome. Furthermore, we generated pig strains expressing the multiplexable CRISPR-Cas-gRNA via germline genome editing and demonstrated that the gene-edited pigs were more resistant to ASFV infection and less likely to spread the virus upon infection. As far as we know, our study presents the first living organism generated via germline editing to demonstrate resistance to viral infection via CRISPR-Cas. We anticipate our work to be helpful for both agricultural and biomedical applications, such as xenotransplantation.
The defence island repertoire of the Escherichia coli pan-genome
Authors: Hochhauser Dina , Millman Adi , Sorek Rotem
Published: June 2022

In recent years it has become clear that anti-phage defence systems cluster non-randomly within bacterial genomes in so-called “defence islands”. Despite serving as a valuable tool for the discovery of novel defence systems, the nature and distribution of defence islands themselves remain poorly understood. In this study, we comprehensively mapped the repertoire of defence islands within >1,300 strains of Escherichia coli, the most widely studied organism in terms of phage-bacteria interactions. We found that defence islands preferentially integrate at several dozens of dedicated integration hotspots in the E. coli genome. Defence islands are usually carried on mobile genetic elements including prophages, integrative conjugative elements and transposons, as well as on other genetic elements whose nature of mobilisation is unclear. Each type of mobile genetic element has a preferred integration position but can carry a diverse variety of defensive cargo. On average, an E. coli genome has 4.5 genomic hotspots occupied by a defence system-containing mobile element, with some strains possessing up to eight defensively occupied hotspots. Our data show that the overwhelming majority of the E. coli pan-immune system is carried on mobile genetic elements that integrate at a discrete set of genomic hotspots, and explains why the immune repertoire substantially varies between different strains of the same species.
Serine Racemase mediates Subventricular Zone Neurogenesis via Fatty acid Metabolism
Authors: Roychaudhuri Robin , Atashi Hasti , Snyder Solomon H.
Published: June 2022

The adult subventricular zone is one of the two neurogenic niches that continuously produce newborn neurons. Here we show that serine racemase (SR), an enzyme that catalyzes the racemization of L-serine to D-serine and vice versa, affects neurogenesis in the adult SVZ by controllingde novofatty acid synthesis. Complete and conditional deletion of SR in nestin precursor cells lead to diminished neurogenesis in the SVZ. Nestin-cre+ mice showed reduced expression of fatty acid synthase and its substrate malonyl CoA, which are involved inde novofatty acid synthesis. Global lipidomic analyses revealed significant alterations in lipid subclasses in nestin-cre+ mice. Decrease in fatty acid synthesis was mediated by phospho acetyl CoA carboxylase that was AMPK independent. Both L and D serine treatment rescued defects in SVZ neurogenesis, proliferation and levels of malonyl CoAin vitro. Our work shows that SR affects adult neurogenesis in the SVZ via lipid metabolism.
Strengthening of enterococcal biofilms by Esp
Authors: Spiegelman Lindsey , Bahn-Suh Adrian , Montaño Elizabeth T. , Zhang Ling , Hura Greg L. , Patras Kathryn A. , Kumar Amit , Tezcan Akif , Nizet Victor , Tsutakawa Susan , Ghosh Partho
Published: June 2022

Multidrug-resistant (MDR)Enterococcus faecalisare major causes of hospital-acquired infections. Numerous clinical strains harbor a large pathogenicity island that encodes enterococcal surface protein (Esp), which is suggested to promote biofilm production and virulence, but this remains controversial. To resolve this issue, we characterized the Esp N-terminal region, the portion implicated in biofilm production. Small angle X-ray scattering indicated that the N-terminal region had a globular head, which consisted of two DEv-Ig domains as visualized by X-ray crystallography, followed by an extended tail. The N-terminal region was not required for biofilm production but instead significantly strengthened biofilms against mechanical or degradative disruption, greatly increasing retention ofEnterococcuswithin biofilms. Biofilm strengthening required low pH, which resulted in Esp unfolding, aggregating, and forming amyloid-like structures. The pH threshold for biofilm strengthening depended on protein stability. A truncated fragment of the first DEv-Ig domain, plausibly generated by a host protease, was the least stable and sufficient to strengthen biofilms at pH ≤ 5.0, while the entire N-terminal region and intact Esp on the enterococcal surface was more stable and required a pH ≤ 4.3. These results suggested a virulence role of Esp in strengthening enterococcal biofilms in acidic abiotic or host environments.
Global Profiling of c-Jun and JunB transcription factor binding sites in an ALK+ ALCL cell line
Authors: Wu Zuoqiao , Nicoll Mary , Facundo Farynna Loubich , Zhang Jingxi , Ingham Robert J.
Published: June 2022

Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is a T cell lymphoma which features translocations or inversion involving the ALK tyrosine kinase gene, and results in oncogenic fusion proteins (e.g. NPM-ALK). The elevated expression and/or activation of activator protein-1 (AP-1) transcription factors, c-Jun and JunB, is another molecular feature of ALK+ ALCL. c-Jun/JunB transcriptional targets are important in the pathobiology of this lymphoma, and several are also therapeutic targets. To better understand c-Jun/JunB function in ALK+ ALCL, we performed chromatin immunoprecipitation–sequencing experiments in the Karpas 299 ALK+ ALCL cell line to comprehensively identify sites bound by these transcription factors. We identified 13,083 c-Jun and 40,369 JunB binding sites, and ∼60% of sites bound by c-Jun were shared with JunB. Many sites were associated with genes known or predicted to be important in the pathogenesis of ALK+ ALCL. Pathway enrichment analysis of genes associated with both c-Jun and JunB binding sites revealed a significant over-representation for pathways associated with cancer and cell signalling. Furthermore, we identified several c-Jun and JunB binding sites associated with the NIBAN2/FAM129B gene. FAM129B is a PH domain-containing phosphoprotein that promotes proliferation in multiple cell types. However, while we found that FAM129B knock-down resulted in modest cell cycle alteration in most ALK+ ALCL cell lines, this did not appear to result in a significant proliferation defect. Finally, we found that inhibition of NPM-ALK and MEK/Erk signalling altered FAM129B electrophoretic mobility and decreased phosphorylation of FAM129B on serine residues known to be Erk phosphosites. In summary, this study is the first to globally profile sites bound by c-Jun/JunB in ALK+ ALCL. It reveals novel putative targets for these transcription factors in ALK+ ALCL, and identifies FAM129B as a novel phosphoprotein downstream of NPM-ALK signalling.
Salicaceae as potential host plants ofXylella fastidiosain European temperate regions
Authors: Casarin Noemi , Hasbroucq Séverine , Pesenti Lena , Géradin Amandine , Emond Amélie , López-Mercadal Júlia , Miranda Miguel Ángel , Grégoire Jean-Claude , Bragard Claude
Published: June 2022

The discovery of three subspecies ofXylella fastidiosain Europe has triggered major attention on the potential spread up North of the bacteria. Assessing the susceptibility of a previously unexposed European flora is a key element that remains widely unknown. Under biosafety facility, we evaluated the susceptibility of Salicaceae such asPopulus tremula, Populus canescens, Salix albaandSalix capreaby mechanically inoculating the KLN59.3 GFP-labelledX. fastidiosaat 22 °C and at 28 °C. Bacterial movement and multiplication in plants were investigated by PCR, real-time PCR, confocal or scanning electron microscopy. Nine months post-inoculation, 100 % of the plants tested positive forX. fastidiosa, with the exception of 57% forP. canescensunder the 22 °C-growing conditions. Bacteria were detected up to 120 cm from the inoculation point forS. alba. They were detected in the roots of all species and were successfully isolated forS. albaandP. tremula. Estimates of average CFU/g of plant tissue per species ranged from 1.5E + 03 to 3.5E + 06, with the lowest figures forP. canescensand the highest forP. tremulatogether with high number of totally obstructed vessels observed by confocal microscopy. The possibility of insect transmission was also evaluated using an experimental set up based on Mallorca Island. There, transmission byP. spumariusof bothX. fastidiosaST1 and ST81 was proven onS. alba. We thus demonstrated that indigenous European Salicaceae such asS. albaorP. tremulaare new potential hosts forX. fastidiosa.
Women directors, educational background and firm value of Spanish listed companies
Authors: Molinero-Díez Patricia , Blanco-Mazagatos Virginia , Garcia-Rodriguez Inigo , Romero-Merino M. Elena
Published: June 2022

Purpose

This study aims to evaluate changes in the presence of women on Spanish boards after the Unified Good Governance Code of Listed Companies (2006) and the Organic Law 3/2007 on Gender Equality, and this study compares the educational background of women and men directors. Also, this study analyses the influence of gender diversity and educational background of women directors on economic performance, corporate social responsibility (CSR) and, ultimately, firm value. In addition, this study explores the differences in board gender composition and its effect on firm value during the crisis and post-crisis periods. Finally, this study analyses the different influence of women directors depending on their typology.

Design/methodology/approach

This study uses a system of structural equations and a sample of 4,101 directors of 30 Spanish companies listed on IBEX-35 over 2008–2017.

Findings

The results show that women’s presence on boards has grown since 2008, and they have higher educational background than men. This study finds that women directors improve economic performance and CSR, though results are non-significant for firm value. Women directors with a bachelor’s or master’s degree increase economic and social performance but reduce firm value. Women directors with business or industry-related studies positively influence CSR but business specialisation negatively affects economic performance and firm value.

Originality/value

This study analyses the direct and indirect effect of women directors on firm value, the influence of their educational background and the potential differences arising from the economic situation (crisis) and the type of board position they hold.
An institutional theory perspective on the role of project management associations for projectification of society: the case of Germany
Authors: Wagner Reinhard , Huemann Martina , Radujković Mladen
Published: June 2022

Purpose

This paper aims to provide insights into the role of project management associations for the projectification of society from an institutional theory perspective.

Design/methodology/approach

The paper is based on a mixed methods approach. It draws on the research propositions of a recently conducted qualitative study and builds on them by analyzing the empirical data of a quantitative case study.

Findings

The results indicate that the projectification of society in Germany is well advanced and continues growing. The economy plays a leading role, which resonates with other sectors of society. The actions of project management associations have only an indirect influence on the projectification of society, which cultural–cognitive institutions are mediating. Both findings are novel compared to the literature.

Practical implications

Taking an overall view of the findings, project management associations gain a better understanding of the projectification process and important guidance on their role.

Social implications

The results offer all people interested intriguing insights into the contemporary phenomenon of the projectification of society, along with its current state and future evolution.

Originality/value

The application of institutional theory to the projectification of society in the framework of this case study enables an in-depth analysis of the underlying social processes and interactions between the regulative, normative and cultural–cognitive activities of project management associations on the one hand, and institutions on the other hand, at the societal level. This opens up new and promising perspectives for further research.
What do expectations change? Optimistic expectations, job crafting, job satisfaction and a new theoretical model
Authors: Yeşilkaya Mukaddes , Yıldız Tayfun
Published: June 2022

Purpose

The purpose of this study is to determine the effect of optimistic expectations on job satisfaction at work and whether job crafting behaviour plays a mediating role in this effect. At the same time, this model presents the need for “expectation management” in the context of work psychology to the attention of all academics and practitioners.

Design/methodology/approach

To test the hypotheses of the study, data were obtained from 475 health-care workers in a public hospital. Hypotheses were tested using Process Macro Model of Hayes (2018).

Findings

The result of the analyses determined that the optimistic expectations for the organization as a whole have a positive effect on job satisfaction, both directly and indirectly, and that job crafting behaviour has a partial mediating role in this effect.

Research limitations/implications

The first limitation is that the data were obtained only by a cross-sectional method. The second is that among the various workplace behaviours and workplace psychologies job crafting and job satisfaction were examined in the study. The partial mediation effect between the research variables reveals the existence of many other variables and constitutes the third limitation. The fourth is that only optimistic expectations effects on positive behaviours and positive psychological states were evaluated in this study. Finally, a fifth limitation of this study is that the sample is limited to those working in the health sector and public hospitals.

Practical implications

First, the data were obtained only by a cross-sectional method, and the longitudinal method was not implemented in how the study was designed. Second, among the workplace behaviours, only job crafting behaviour and only job satisfaction as a workplace psychology were analysed. Third, partial mediation effect was found to be among the other variables might indicate the role of additional variables that could be uncovered by further research. Fourth, only optimistic expectations and their effects on positive behaviours and positive psychological states at the workplace were evaluated. Fifth, the sample is limited to those working in the health sector and public hospitals.

Social implications

This study draws attention to “Expectation Management” as a management activity worth exploring and its potential in terms of social and working relations.

Originality/value

This study provides versatile answers to the question of why individuals perform differently despite working under the same conditions. The model suggested in the study takes the conventional way of thinking in the literature one step further by offering an alternative answer to this critical question, whose answers we have been discovering step by step since the Hawthorne studies. In addition, the proposed model draws attention to the need for “expectation management” in the context of business psychology in theory and practice.
Social capital and loan credit terms: does it matter in microfinance contract?
Authors: Iqbal Zahid , Rao Zia-ur-Rehman
Published: June 2022

Purpose

To enhance the loan repayment performance of microfinance institutions (MFIs) in Pakistan, this study aims to analyze the direct impact of social capital and loan credit terms on loan repayment performance and microenterprises’ business performance while considering the mediating role of microenterprises’ business performance on the relationship between social capital, loan credit terms and loan repayment performance.

Design/methodology/approach

The analysis was conducted based on the data gathered via a questionnaire distributed to 316 microenterprises owners. The respondents were selected using the stratified sampling technique by dividing the target population into three influential groups of manufacturing, trading and services microenterprises. The reliability and validity of the constructs were established using (1) factor loading, (2) Cronbach’s alpha, (3) composite reliability, (4) average variance extracted, (5) the variance inflation factor, (6) the Fornell–Larcker criterion and (7) the heterotrait–monotrait ratio. The structural equation modeling technique was then applied, and the hypotheses were tested based on the structure model generated through bootstrapping by using partial least squares structural equation modeling.

Findings

The results confirm the direct impact of social capital and loan credit terms on microenterprises’ business performance and loan repayment performance. It also supports the mediating role of microenterprises’ business performance toward the relationship between social capital, loan credit terms and loan repayment performance while considering the direct impact of microenterprises’ business performance on loan repayment performance.

Originality/value

To date, the direct impact of social capital and loan credit terms on microenterprises’ business performance and loan repayment performance has been hardly investigated in the context of Pakistan. This study also examines the mediating role of microenterprises’ business performance toward social capital, loan credit terms and loan repayment performance. The findings will enable both MFIs and microenterprises to improve their business performance and loan repayment performance through enhanced social ties and the development of more flexible credit products that protect the borrowers’ interests and the interest of lenders.
Health insurers: evolving into ecosystem-based service companies
Authors: Jahn Justin , Bohnet-Joschko Sabine
Published: June 2022

Purpose

This study aims to investigate whether health insurers are transforming from pure payers into ecosystem-based health service companies. The authors discuss the findings’ impact on health insurers’ business model approach and their sources of competitive advantage.

Design/methodology/approach

The authors conducted a multiple case study of 25 incumbent and rising health insurers from the USA, Europe and Asia-Pacific. The selection of firms was based on databases from Forbes, S&P Global Market Intelligence and Crunchbase. By performing a review of financial reports, app descriptions, corporate websites and media coverage, the authors analyzed health insurers’ digital service offerings and underlying strategic approaches for providing those services.

Findings

This study demonstrates that major health insurers are transforming into ecosystem-based health service companies. They expand the traditional insurance value chain by offering value-adding health services along the patient journey. The analysis results are summarized in a table displaying 18 digital service categories along core patient journey phases with corresponding examples of health insurers and underlying strategic approaches.

Originality/value

The role of digital services and ecosystems has been explored for many industries. This study investigates this subject area with a focus on the health insurance sector, advancing a young field of research. The analysis gives insights into the latest digital service offerings and strategic approaches of an internationally diverse set of incumbents and rising ventures.
Quantifying the impact of early-stage maintenance clustering
Authors: Agergaard Julie Krogh , Sigsgaard Kristoffer Vandrup , Mortensen Niels Henrik , Ge Jingrui , Hansen Kasper Barslund
Published: June 2022

Purpose

The purpose of this paper is to investigate the impact of early-stage maintenance clustering. Few researchers have previously studied early-stage maintenance clustering. Experience from product and service development has shown that early stages are critical to the development process, as most decisions are made during these stages. Similarly, most maintenance decisions are made during the early stages of maintenance development. Developing maintenance for clustering is expected to increase the potential of clustering.

Design/methodology/approach

A literature study and three case studies using the same data set were performed. The case studies simulate three stages of maintenance development by clustering based on the changes available at each given stage.

Findings

The study indicates an increased impact of maintenance clustering when clustering already in the first maintenance development stage. By performing clustering during the identification phase, 4.6% of the planned work hours can be saved. When clustering is done in the planning phase, 2.7% of the planned work hours can be saved. When planning is done in the scheduling phase, 2.4% of the planned work hours can be saved. The major difference in potential from the identification to the scheduling phase came from avoiding duplicate, unnecessary and erroneous work.

Originality/value

The findings from this study indicate a need for more studies on early-stage maintenance clustering, as few others have studied this.
How do we design and conduct cross-language research? A reflexive approach building on Squires' criteria
Authors: Jeong Daeul
Published: June 2022

Purpose

This paper demonstrates complexity surrounding cross-language research involving an interpreter and illustrates how the author attempted to ensure methodological rigor through modifying and applying Squires' criteria to the design and conduct of her education research.

Design/methodology/approach

This research employed Squires' recommendations for cross-language research as methodological guidelines for designing and conducting cross-language research. The research involved focus group discussions with teachers working in an ethnic minority boarding school in Laos and an interpreter who helped translating/transcribing interviews in Lao to English and data analysis.

Findings

From applying Squires' criteria, this paper introduces a reflexive set of recommendations for researchers conducting a wide range of qualitative cross-language research.

Originality/value

Most meta-criteria for cross-language research are developed to evaluate the quality of cross-language research. However, the soundness of a set of meta-criteria as one tool to evaluate all cross-language research might be questionable due to qualitative studies' diverse epistemological grounds. This paper argues that meta-criteria can serve as a critical and reflexive guide for cross-language researchers when used from the research design and on. The paper also suggests a new set of recommendations which may facilitate more reflexive approaches to cross-language research.