bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-content high-resolution microscopy and deep learning assisted analysis reveals host and bacterial heterogeneity duringShigellainfection
Authors: López-Jiménez Ana T. , Brokatzky Dominik , Pillay Kamla , Williams Tyrese , Güler Gizem Özbaykal , Mostowy Serge 
Published: March 2024

AbstractShigella flexneriis a Gram-negative bacterial pathogen and causative agent of bacillary dysentery.S. flexneriis closely related toEscherichia colibut harbors a virulence plasmid that encodes a Type III Secretion System (T3SS) required for host cell invasion. Widely recognized as a paradigm for research in cellular microbiology,S. flexnerihas emerged as important to study mechanisms of cell-autonomous immunity, including septin cage entrapment. Here we use high-content high-resolution microscopy to monitor the dynamic and heterogeneousS. flexneriinfection process by assessing multiple host and bacterial parameters (DNA replication, protein translation, T3SS activity). In the case of infected host cells, we report a reduction in DNA and protein synthesis together with morphological changes that suggestS. flexnerican induce cell-cycle arrest. We developed an artificial intelligence image analysis approach using Convolutional Neural Networks to reliably quantify, in an automated and unbiased manner, the recruitment of SEPT7 to intracellular bacteria. We discover that heterogeneous SEPT7 assemblies are recuited to actively pathogenic bacteria with increased T3SS activation. Our automated microscopy workflow is useful to illuminate host and bacterial dynamics at the single-cell and population level, and to fully characterise the intracellular microenvironment controlling theS. flexneriinfection process.
The Association Between Parental BMI and Offspring Adiposity: A Genetically Informed Analysis of Trios
Authors: Wright Liam , Shireby Gemma , Morris Tim T. , Davies Neil M. , Bann David 
Published: March 2024

AbstractBackgroundChildren with obesity are more likely to have parents with obesity, too. Several environmental explanations have been proposed for this correlation, including foetal programming, and parenting practices. However, body mass index (BMI) is a highly heritable trait; child-parent correlations may reflect direct inheritance of adiposity-related genes. There is some evidence that mother’s BMI associates with offspring BMI net of direct genetic inheritance, consistent with both intrauterine and parenting effects, but this requires replication. Here we also investigate the role of father’s BMI and diet as a mediating parenting factor.MethodsWe used Mendelian Randomization (MR) with genetic trio (mother-father-offspring) data from 2,621 families in the Millennium Cohort Study, a UK birth cohort study of individuals born in 2001/02, to examine the association between parental BMI (kg/m2) and offspring birthweight and BMI and diet measured at six-time points between ages 3y and 17y. Paternal and maternal BMI were instrumented with polygenic indices (PGI) for BMI also conditioning upon offspring PGI. This allowed us to separate direct and indirect (“genetic nurture”) genetic effects. We compared these results with associations obtained using multivariable regression techniques using phenotypic BMI data only, the standard research approach.ResultsMother’s and father’s BMI were positively associated with offspring BMI to similar degrees. However, in MR analysis, associations between father’s BMI and offspring BMI were close to the null, suggesting phenotypic associations reflect the direct transmission of genetic traits. In contrast, mother’s BMI was consistent in MR analysis with phenotypic associations. Maternal indirect genetic effects were between 20-50% the size of direct genetic effects. There was inconsistent evidence of associations with offspring diet. Mother’s, but not father’s, BMI was related to birthweight in both MR and multivariable regression models.ConclusionResults suggest that maternal BMI may be particularly important for offspring BMI: associations may arise due to both direct transmission of genetic effects and indirect (genetic nurture) effects. Associations between father’s and offspring adiposity that do not account for direct genetic inheritance may yield severely biased estimates of paternal influence.
Deciphering lentiviral Vpr/Vpx determinants required for HUSH and SAMHD1 antagonism highlights the molecular plasticity of these evolutionary conflicts
Authors: Larrous Pauline , Garnier Cassandre , Morel Marina , Martin Michael M. , Zarrouk Karima , Maesen Sarah , Matkovic Roy , Cimarelli Andrea , Etienne Lucie , Margottin-Goguet Florence 
Published: March 2024

ABSTRACTSAMHD1 and the HUSH complex constitute two blocks during primate lentivirus infection, the first by limiting reverse transcription and the second by inhibiting proviral expression. Vpr and Vpx of specific lentiviral lineages have evolved to antagonize these antiviral proteins. While the antagonism of SAMHD1 has been well characterized, the evolutionary and molecular determinants of the antagonism against HUSH are unknown. We used chimeric Vpr proteins between SIVagm.Ver and SIVagm.Gri lentiviruses infecting two African green monkey species, to investigate viral determinants involved in HUSH and SAMHD1 antagonisms. We found that different interfaces of closely related Vpr proteins are engaged to degrade different SAMHD1 haplotypes. In addition, we identified distinct viral determinants in SIVagm.Ver Vpr for SAMHD1 and HUSH degradation. The substitution of one residue in SIVagm.Gri Vpr is sufficient to gain the capacity to degrade SAMHD1, while the substitution of α-helix-3 confers HUSH antagonism. We also found that Vpx proteins of HIV-2 from people living with HIV have different abilities to degrade HUSH. These phenotypes rely on small changes in either the N or C terminal part of Vpx, depending on the context. On the host side, we found that HIV-2 and SIVsmm Vpx degrading HUSH from human and vervet monkey cells cannot not degrade HUSH in owl monkey cells, suggesting some host species-specificity.Altogether, we highlight the molecular plasticity and constraints of viral proteins to adapt to host restrictions. HUSH, like SAMHD1, may have been engaged in ancient and more recent coevolution with lentiviruses and a player in viral fitness.IMPORTANCEAntiviral host proteins, the so-called restriction factors, block lentiviruses at different steps of their viral life cycle. In return, primate lentiviruses may counteract these immune proteins to efficiently spreadin vivo. HIV-2 and some SIVs, but not HIV-1, inactivate SAMHD1 and HUSH, two host antiviral proteins, thanks to their Vpx or Vpr viral proteins. First, we uncovered here viral determinants involved in the function of closely related Vpr proteins from SIVs of African green monkeys and of HIV-2 Vpx alleles from people living with HIV-2. We show how these small viral proteins differently adapted to SAMHD1 polymorphism or to HUSH restriction and highlight their molecular plasticity. Finally, the capacity of divergent lentiviral proteins, including HIV-2 Vpx, to induce the degradation of HUSH depends of the cell/host species. Altogether, our results suggest that HUSH has been engaged in a molecular arms-race along evolution, and therefore is a key player in host-pathogens interaction.
CemR atypical response regulator impacts energy conversion inCampylobacteria
Authors: Noszka Mateusz , Strzałka Agnieszka , Muraszko Jakub , Hofreuter Dirk , Abele Miriam , Ludwig Christina , Stingl Kerstin , Zawilak-Pawlik Anna 
Published: March 2024

AbstractCampylobacter jejuniandArcobacter butzleriare microaerobic food-borne human gastrointestinal pathogens that mainly cause diarrheal disease. These related species of theCampylobacteriaclass face variable atmospheric environments during infection and transmission, ranging from nearly anaerobic to aerobic conditions. Consequently, their lifestyles require that both pathogens need to adjust their metabolism and respiration to the changing oxygen concentrations of the colonization sites. Our studies revealed thatC. jejuniandA. butzlerilacking aCampylobacteria-specific regulatory protein,C. jejuniCj1608 or a homologueA. butzleriAbu0127, are unable to reprogram tricarboxylic acid cycle or respiration pathways, respectively, to produce ATP efficiently and, in consequence, adjust growth to changing oxygen supply. We propose that theseCampylobacterialenergy and metabolism regulators (CemR) are long-sought transcription factors controlling the metabolic shift related to oxygen availability, essential for these bacteria’s survival and adaptation to the niches they inhabit.
Differential CheR affinity for chemoreceptor C-terminal pentapeptides biases chemotactic responses
Authors: Velando Félix , Monteagudo-Cascales Elizabet , Matilla Miguel A. , Krell Tino 
Published: March 2024

SummaryThe capacity of chemotaxis pathways to respond to signal gradients relies on adaptation mediated by the coordinated action of CheR methyltransferases and CheB methylesterases. Many chemoreceptors contain a C-terminal pentapeptide at the end of a linker. InEscherichia coli,this pentapeptide forms a high-affinity binding site for CheR and phosphorylated CheB, and its removal interferes with adaptation. The analysis of all available chemoreceptor sequences showed that pentapeptide sequences vary greatly, and bacteria often possess multiple chemoreceptors that differ in their pentapeptide sequences. Using the phytopathogenPectobacterium atrosepticumSCRI1043, we assessed whether this sequence variation alters CheR affinity and chemotaxis. SCRI1043 has 36 chemoreceptors, of which 19 possess a C-terminal pentapeptide. Using isothermal titration calorimetry, we show that the affinity of CheR for the different pentapeptides varies up to 11-fold (KDof 90 nM to 1 µM). The pentapeptides with the highest and lowest affinities differed only in a single amino acid. Deletion of thecheRgene abolishes chemotaxis. PacC is the sole chemoreceptor for L-Asp in SCRI1043, and the replacement of its pentapeptide with those having the highest and lowest affinities significantly interfered with L-Asp chemotaxis. Variable pentapeptide sequences thus provide a mechanism to bias the responses mediated by chemoreceptors.
Probing recombinant AAV capsid integrity and genome release under thermal stress by single-molecule interferometric scattering microscopy
Authors: Ebberink Eduard H.T.M. , Ruisinger Alisa , Nuebel Markus , Meyer-Berg Helena , Ferreira Irene R.S. , Thomann Marco , Heck Albert J.R. 
Published: March 2024

AbstractAdeno-associated viruses (AAVs) are gaining traction as delivery vehicles for gene therapy although the molecular understanding of AAV-transgene release is still limited. Typically, the process of viral uncoating is investigated (in vitro) through thermal stress, revealing capsid disintegration at elevated temperatures. Here, we used single-molecule interferometric scattering microscopy to assess the (in)stability of different empty and filled AAV preparations. By introducing a heat-stable DNA plasmid as an internal standard, we quantitatively probed the impact of heat on AAVs. Generally, empty AAVs exhibited greater heat resistance than genome-filled particles. Our data also indicate that upon DNA release, the capsids do not transform into empty AAVs, but seem to aggregate or disintegrate. Strikingly, some AAVs exhibited an intermediate state with disrupted capsids but preserved bound genome, a feature that experimentally only emerged following incubation with a nuclease. Our data demonstrate that the thermal uncoating process is highly AAV specific (i.e., can be influenced by serotype, genome, host system). We argue that nuclease treatment in combination with mass photometry can be used as an additional analytical tool for assessing structural integrity of recombinant and/or clinical AAV vectors.
The barriers to advancing race equality in Scottish local authority employment
Authors: Hofmann Silvio 
Published: March 2024

PurposeThis paper critically evaluates potential barriers to employment opportunities for ethnic minority (EM) individuals in Scottish Local Authorities – both in terms of access to job and development opportunities. It provides a fundamental discussion of concepts around race and ethnicity, and the levels of social injustice, with an explicit focus on institutional racialisation, discrimination and segregation. The paper explores organisational approaches towards recruitment, including positive action and workforce development.Design/methodology/approachThis paper adopts a subjectivist (ontology) and interpretivist (epistemology) stance, based on a small-scale, in-depth investigation. The data have been gathered through semi-structured interviews with equality diversity and inclusion (EDI) officers in four Scottish Local Authorities, utilising thematic analysis.FindingsThe finding suggests that participating local authorities have a long way to go to ensure the elimination of barriers to employment for EM people. This is largely based on concerns around limitations in the application of positive action and elimination of disadvantages in recruitment and access to career and development opportunities?Originality/valueThe paper aims to contribute by exploring the availability of employment opportunities for EMs through the eyes of EDI Officers in four local authorities. Their thorough understanding, over- and insight into potential equality issues from an employment perspective are invaluable, focussing on more tangible organisational issues and approaches.
Corporate entrepreneurship and family businesses: a perspective article
Authors: Bravo Monge Cris 
Published: March 2024

PurposeFamily businesses play a pivotal role in the world’s economy, contributing to 70% of its GDP. Their success in the current environment demands the enactment of entrepreneurial and innovative competencies to catalyse organizational growth and performance. In this context, corporate entrepreneurship may help these organizations advance their competitive advantage. The systematic analysis of the past 50 years of research reveals that a broad range of variables may moderate relationships among antecedents, outcomes and corporate entrepreneurship. This article aims to explore future avenues of research that will contribute to a better understanding of corporate entrepreneurship in family firms.Design/methodology/approachThis paper is based on the systematic research.FindingsWhile the synergy between corporate entrepreneurship and family business has gained attention, the intricacies and nuances within this intersection remain largely unexplored due to the diverse nature of corporate entrepreneurship and family enterprises. Future research endeavours in this domain should aim to explore fundamental aspects, including refining the definition of corporate entrepreneurship, understanding its interplay with familiness, socioemotional wealth, national and organizational culture and other various family-related factors such as the composition of the top management team, organizational size, diversity and attitudes towards risk.Research limitations/implicationsBy outlining the key variables such as familiness, socioemotional wealth, generational involvement and cultural factors, the paper guides future research efforts. Researchers and practitioners can use these identified variables as focal points for deeper investigation and analysis when exploring the dynamics of corporate entrepreneurship within family businesses.Practical implicationsFamily firm managers may apply instruments like the Corporate Entrepreneurship Assessment Instrument together with other instruments like the Family Influence Familiness Scale (FIFS) and the FIBER instrument to obtain an indication of a firm’s likelihood of being able to successfully implement an entrepreneurial climate within the firm.Social implicationsFamily businesses represent 70% of the world’s GDP, therefore, improving the understanding of how corporate entrepreneurship augments their resilience and competitiveness, may contribute to the well-being of 60% of the global workforce.Originality/valueThe paper synthesizes the research in corporate entrepreneurship in family businesses and proposes a future perspective.
Institutional Logics, Risk and Extreme Events: Insights from and for Management Education
Authors: Wright April L. , Pereira Sandra , Berrington Catherine , Felstead David , Staggs Jonathan 
Published: March 2024

AbstractTo shed light on the interrelationship between risk and logics, we explore how multiple institutional logics shape management educators’ experiences of risk in classroom teaching. Using a two‐case research design, we analyse an empirical case study of management educators in a UK business school during the COVID‐19 pandemic and a case study of emergency physicians during the Ebola epidemic. Comparing these two focal cases of different types of frontline professional work during global health crises, we develop a model of how perceptions of risks and their mitigation shape, and are shaped by, experiences of compatibility, contestation and rejection among multiple logics. Our study extends the literatures on institutional logics and risk by providing insight into the role of multiple logics in the social construction of risk. We also contribute to the management education literature by focusing attention on the risks of physical harm in classroom teaching and by theorizing when, how and why management educators apprehend these risks as ordinary or extraordinary to their normal professional role. Finally, our study has practical implications for risk mitigation at individual and organizational levels and for creatively and safely adapting teaching and learning practices with students during extreme events.
Cross‐country comparisons in health price growth over time
Authors: Papanicolas Irene , Cylus Jonathan , Lorenzoni Luca 
Published: March 2024

AbstractObjectiveTo examine how the United States compares in terms of health price growth relative to four other countries ‐ Australia, Canada, France, and the Netherlands.Data Sources and Study SettingSecondary data on health expenditure were extracted from international and national agencies spanning the years 2000–2020.Study DesignInternational price indices specific to health were constructed using available international expenditure data and compared to existing health‐specific national and general international price indices.Data Collection/Extraction MethodsHealth expenditure data were extracted from the Organization for Economic Cooperation and Development (OECD) database. We obtained a time series of health price indices from the national agencies in each of the study countries.Principal FindingsWe find meaningful variation across countries in the rate at which health prices grow relative to general prices. The United States had the highest cumulative health price growth compared to general price growth over the years 2000–2020 at 14%, followed by Canada and the Netherlands. Unlike the other study countries, health prices in France grew consistently in line with general prices. Price growth for health care paid for by public funds and households grew at different rates across countries, where price growth was higher for public payers. US households faced the greatest mean annual price growth.ConclusionsThe choice of price index has major implications for comparative analysis. Despite their widespread use internationally, general price indices likely underestimate the contribution of price growth to overall health expenditure growth. We find that in addition to its reputation for having high health price levels compared to other high‐income countries, the United States also faces health price growth for goods and services paid for by government and households in excess of general price growth. Furthermore, US households are exposed to greater health price growth than households in comparator countries.
Shelf‐life extension of Pacific white shrimp (Litopenaeus vannamei) using sodium alginate/chitosan incorporated with cell‐free supernatant of Streptococcus thermophilus FUA 329 during cold storage
Authors: Zhao Shuangshuang , Bian Yingying , Zhang Gewen , Yang Guang , Hou Xiaoyue , Gui Jiajin , Mu Shuting , Liu Shu , Fang Yaowei 
Published: March 2024

AbstractSeafood is highly perishable and has a short shelf‐life. This study investigated the effect of chitosan and alginate (CH‐SA) coating combined with the cell‐free supernatant of Streptococcus thermophilus FUA329 (CFS) as a preservative on the quailty of white shrimp (Litopenaeus vannamei) refrigerated at 4° for 0, 3, 6, 9, 12, 15 days. Freshly shrimps were randomly divided into four groups: the CFS group (400 mL); the CH‐SA group (1% chitosan/1% alginate); the CFS‐CH‐SA group (1% chitosan/1% alginate with 400 mL CFS) are treatment groups, and the control group (400 mL sterile water). The CFS–CH–SA coating effectively suppressed microbial growth total viable count and chemical accumulation (pH, total volatile basic nitrogen, thiobarbituric acid reactive substance) compared with the control. Additionally, the CFS–CH–SA coating improved the texture and sensory characteristics of shrimp during storage. The coated shrimp exhibited significantly reduced water loss (p < 0.05). The combination of CH–SA coating with CFS treatment can extend the shelf life of shrimp.Practical ApplicationRecently, edible films have received more consideration as a promising method to enhance the shelf life of seafood. The presence of Lactic acid bacteria metabolites in edible films reduces spoilage and improves consumer health. Our findings encourage the application of edible coating incorporated with cell‐free supernatant of Streptococcus thermophilus FUA 329 to design multifubctional foods and preserve the qualities of shrimp.
Factors associated with acute anterior uveitis history in patients with axial spondyloarthritis: Results of a longitudinal study
Authors: Cinakli Haluk , Ediboglu Elif Durak , Solmaz Dilek , Akar Servet 
Published: March 2024

AbstractBackgroundsAcute anterior uveitis (AAU) is the most common extra‐musculoskeletal manifestation in axial spondyloarthritis (axSpA).ObjectivesThe aim of the study is to evaluate the factors associated with AAU attacks in patients with axSpA during a 36‐month follow‐up period.MethodsIn total, 469 patients with axSpA were included in this observational study. Demographic data, clinical characteristics, disease activity measurements, and treatment patterns were compared between patients with and without a history of AAU. The development of AAU and its related factors were investigated using generalized estimating equations, which is a technique for longitudinal data analysis.ResultsOverall, 99 (21%) out of 469 patients experienced at least one AAU attack, with 77 patients (78%) having a history of AAU and 53 patients (58% of whom had a history of AAU) experiencing AAU attacks during the follow‐up period. At baseline, patients with a history of AAU were found to be older (p = .001), be more likely to have peripheral arthritis (p < .001), have higher serum CRP levels (p = .016), have a higher frequency of sulfasalazine (SLZ) and tumor necrosis factor inhibitors (TNFi) use (p < .001 and p < .001, respectively). In the longitudinal analysis, having a history of AAU was identified as the only independent determinant of the development of AAU.ConclusionsAAU history might be a risk factor for the development of AAU attacks in patients with axSpA. Although TNFi and SLZ were prescribed more frequently to patients with a history of AAU, the effectiveness of these agents in preventing further AAU attacks was not demonstrated.