bluuebunny/crossref_metadata_2025 huggingface dataset:
Synphilin-1 as a modulator of aSyn assembly
Authors: Lázaro Diana F. , Amen Triana , Gerhardt Ellen , Santos Patrícia I. , Milovanovic Dragomir , Höglinger Günter , Outeiro Tiago F.
Published: March 2024

Alpha-synuclein (aSyn) is an intrinsically disordered protein that undergoes phase-separation and is associated with several neurodegenerative conditions. However, the function and the pathological role of aSyn are still elusive. Here, we modeled different types of aSyn assemblies in living cells, and developed a model that reports on gel and solid-like inclusions based on the coexpression of aSyn and synphilin-1 (Sph1). We identified striking morphological differences between aSyn-aSyn and Sph1-aSyn assemblies, characterized by distinct antibody recognition patterns, resistance to Proteinase K treatment, and protein mobilities. Importantly, we showed that the interaction between Sph1-aSyn can be manipulated, altering inclusion size and number. Sph1-aSyn interactions were central for inclusion formation and localization, and that inclusions include lysosomes and AP-1 vesicles, consistent with previous studies in human brain tissue. In total, we provide novel insight into the biology of protein aggregation, shedding light on potential therapeutic strategies that extend beyond conventional targets. Deciphering the role of Sph1 and other aSyn-interacting proteins on aSyn biology and pathobiology will be essential for treating synucleinopathies.
A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies
Authors: Bohórquez José Alejandro , Adduri Sitaramaraju , Ansari Danish , John Sahana , Florence Jon , Adejare Omoyeni , Singh Gaurav , Konduru Nagarjun , Jagannath Chinnaswamy , Yi Guohua
Published: March 2024

Tuberculosis (TB), caused byMycobacterium tuberculosis(Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. Further, co-infections with HIV andMtbhave severe effects in the host, with people infected with HIV being fifteen to twenty-one times more likely to develop active TB. The use of an appropriate animal model for HIV/Mtbco-infection that can recapitulate the diversity of the immune response in humans would be a useful tool for conducting basic and translational research in HIV/Mtbinfections. The present study was focused on developing a humanized mouse model for investigations on HIV-Mtbco-infection. Using NSG-SGM3 mice that can engraft human stem cells, our studies showed that they were able to engraft human CD34+ stem cells which then differentiate into a full-lineage of human immune cell subsets. After co-infection with HIV andMtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally,Mtbcaused infections in both lungs and spleen, and induced the development of granulomatous lesions in the lungs, detected by CT scan and histopathology. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Our results suggest that the humanized NSG-SGM3 mice are able to recapitulate the effects of HIV andMtbinfections and co-infection in the human host at pathological, immunological and metabolism levels, providing a dependable small animal model for studying HIV/Mtbco-infection.
Cohort profile: The WHO Child Mortality Risk Stratification Multi-Country Pooled Cohort (WHO-CMRS) to identify predictors of mortality through early childhood
Authors: Schwinger Catherine , Kaldenbach Siri , Berkley James A. , Walson Judd L. , Argaw Alemayehu , Chowdhury Ranadip , Strand Tor A. , Rollins Nigel
Published: March 2024

Purpose

To provide details of a pooled dataset that will be used to estimate absolute and relative mortality risks and other outcomes among children less than 59 months of age and the predictive performance of common risk exposures, both individually and in combination.

Participants

Children from birth to five years of age recruited at health facilities or community settings into 33 longitudinal observational or intervention studies in 18 low-and middle-income countries.

Findings to date

The dataset includes 75,287 children with a median age of 3 months (IQR 1, 12) at first measurement. In the pooled sample, 2,805 (3.7%) of the study children died. Data on birthweight was recorded in 18 studies, and gestational age in 13 studies. Among these, 14% of the included children were reported with low birthweight and 14% preterm birth. At first measurement, 33% of the children were stunted, 24% were wasted, and 35% underweight. 13% and 7% of caregivers reported that their child had acute diarrhoea or acute lower respiratory tract infection before the study visit, respectively. The proportion of children being breastfed at any study visit decreased from 99% at age <6 months to 77% in the age group 12-23 months. Child characteristics differed considerably between studies in the community and health care settings. The median study period was 15 months (IQR 7.6 to 18.4 months).

Future plans

The WHO Child Mortality Risk Stratification Multi-Country Pooled Cohort (WHO-CMRS) provides a large dataset including child, parental, and household characteristics from a diverse range of geographical, community and health system settings; planned analyses will examine knowledge gaps with the aim of informing global guidelines and their derivatives such as clinical management tools and implementation guidance, and to inform future research agendas.

STRENGTHS AND LIMITATIONS

Strengths

– A large dataset that integrates diverse geographical areas in LMICs, with children recruited from community and health system settings.

– Prospective data collection and availability of key time-varying exposures, such as nutritional status, common childhood morbidities, and feeding practices and non-time varying exposures, such as birth characteristics and socio-demographics.

– Ability to estimate age-specific absolute mortality risks from different exposure domains and combinations thereof.

Limitations

– Non-systematic selection of included datasets.

– Heterogeneity of inclusion criteria, exposures collected and follow-up schedules across studies.
Evaluation of a novel respiratory virus inactivating buffer for parallel RT-qPCR and quick antigen testing
Authors: Deprez Sigrid , Steyaert Sophia , Claeys Mikhail , Verhasselt Ludwig , Vandesompele Jo
Published: March 2024

Since the COVID-19 pandemic, many hospitals implemented a dual testing procedure for SARS-CoV-2 to assess the infection risk of an admitted patient. To allow for a short turn-around time, rapid antigen (Ag) testing via lateral flow tests (LFT) is combined with nucleic acid amplification testing (NAAT), requiring two nasopharyngeal swab collections. In this study, a novel, universal pathogen inactivation buffer (DNA/RNA Defend Pro (DRDP)) was evaluated for SARS-CoV-2 inactivation and simultaneous Ag and DNA/RNA stabilization.

In an emergency department setting of a General Hospital in Ghent (Belgium), patients were tested for SARS-CoV-2, whereby a LFT for Ag detection (Abbott Panbio COVID-19 Ag Rapid Test) was performed in combination with sample collection for NAAT (Abbott Alinity m). Left-over buffers from LFT were diluted in DRDP to evaluate LFT and NAAT results after dilution. Thirty-six patients were included in the data analysis.

Twenty-three diagnostic LFT results were available in the laboratory information system of which all corresponded with results after dilution with DRDP. When correlating NAAT results, seven out of eight positive test results were in agreement, compared to twenty-three out of twenty-five negative results. For thirty-four out of thirty-six samples, LFT and NAAT after dilution with DRDP yielded the same conclusion. Additionally, RNA stability in DRDP was demonstrated when stored for three days at room temperature. At the extreme, a sample stored in the DRDP buffer for 53 days at room temperature was still very positive (Cq 21.95).

We demonstrated that, for the first time, a novel collection buffer could inactivate a pathogen (SARS-CoV-2) while also preserving antigen (for rapid antigen testing) and RNA (for molecular testing). This novel buffer holds promise for a single specimen to be used for both antigen and molecular testing in a safe working environment.
Power spectra density and similarity analysis of COVID-19 mortality waves across countries
Authors: Manjarrez Elias , Delfin Erick F , Dominguez-Nicolas Saul M , Flores Amira
Published: March 2024

Johns Hopkins University CSSE documented waves of oscillatory COVID-19 mortality patterns worldwide during the COVID-19 pandemic. Here, we calculated the power spectrum density (PSD) of these COVID-19 mortality waves in 199 countries from January 22, 2020, to March 9, 2023. We identified two dominant peaks in the grand averaged PSD: one at a frequency of 1.15 waves per year (i.e., one wave every 10.4 months) and another at 2.7 waves per year (i.e., one wave every 4.4 months). Moreover, we performed a cosine similarity analysis of these PSD patterns among all the countries. The results showed a cosine similarity index distribution that was negatively skewed, with a skewness of −0.54 and a global median of cosine similarity index of 0.84, thus revealing a remarkable similarity in the dominant peaks of the COVID-19 mortality waves. These findings could be helpful if a future pandemic of a similar scale occurs so that effective confinement measures or other actions could be planned during these two identified periods, ensuring more assertive public health policies in advance.
Physical and sociocultural factors influencing hand hygiene behavior during COVID-19 pandemic: A cross-sectional study among traders in Lusaka District, Zambia
Authors: Siame Joyce Namukonda , Libonda Liyali , Kanyata Kanyata
Published: March 2024

The COVID-19 epidemiology highlights the challenges for containment, mitigation, and control in low-resource settings like Zambia and suggests that the most vulnerable groups, particularly those living in low-income environments and depending on casual livelihoods, demand attention. This study aimed to determine factors that affect hand hygiene behavior during the COVID-19 Pandemic among traders at the New Soweto Market in Lusaka District. A cross-sectional analytical design was used to quantitatively investigate physical and sociocultural factors that affect hand hygiene behaviour during the COVID-19 pandemic among traders at New Soweto Market in Lusaka District, Zambia. The study sample included a total of 125 registered traders at the New Soweto Market, which is the biggest market in the capital city of Zambia. Majority of the participants (98.1%) demonstrated knowledge on hand hygiene. Remarkably, hand hygiene compliance was significantly associated with acquisition of hand hygiene knowledge [X (6, N = 120) = 41.49, p = 0.000] and cultural customs [X (6, N = 120) = 62.09, p = 0.000]. Further, hand hygiene compliance was significantly associated with availability of hand hygiene services or facilities within the market, [X (6, N = 120) = 13.30, p = 0.038]. Despite this, majority of the participants (61.7%) reported that they did not benefit from any hand hygiene services or facilities from the Local Authority or Ministry of Health. For an effective infection prevention and control program regarding COVID-19 pandemic, relevant authorities should consider supporting traders with hand hygiene related services.
MIXL1 Activation in Endoderm Differentiation of Human Induced Pluripotent Stem Cells
Authors: Osteil Pierre , Withey Sarah , Santucci Nicole , Aryamanesh Nader , Pang Ignatius , Salehin Nazmus , Sun Jane , Qin Annie , Su Jiayi , Knowles Hilary , Li Xiucheng Bella , Cai Simon , Wolvetang Ernst , Tam Patrick P. L.
Published: March 2024

Human induced pluripotent stem cells (hiPSC) possess the ability to differentiate into a multitude of cell and tissue types but display heterogeneous propensity of differentiation into specific lineage. Characterization of the transcriptome of eleven hiPSC lines showed that activation ofMIXL1at the early stage of stem cell differentiation correlated with higher efficacy in generating definitive endoderm and advancing differentiation and maturation of endoderm derivatives. Enforced expression ofMIXL1in the endoderm-inefficient hiPSCs enhanced the propensity of endoderm differentiation, suggesting that modulation of key drivers of lineage differentiation can re-wire hiPSC to the desired lineage propensity to generate the requisite stem cell products.
A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma
Authors: Sussman Jonathan H. , Oldridge Derek A. , Yu Wenbao , Chen Chia-Hui , Zellmer Abigail M. , Rong Jiazhen , Parvaresh-Rizi Arianne , Thadi Anusha , Xu Jason , Bandyopadhyay Shovik , Sun Yusha , Wu David , Hunter C. Emerson , Brosius Stephanie , Ahn Kyung Jin , Baxter Amy E. , Koptyra Mateusz P. , Vanguri Rami S. , McGrory Stephanie , Resnick Adam C. , Storm Phillip B. , Amankulor Nduka M. , Santi Mariarita , Viaene Angela N. , Zhang Nancy , Raedt Thomas De , Cole Kristina , Tan Kai
Published: March 2024

Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that is a leading cause of pediatric cancer death. While pHGG shares many similarities to adult glioma, it is increasingly recognized as a molecularly distinct, yet highly heterogeneous disease. In this study, we longitudinally profiled a molecularly diverse cohort of 16 pHGG patients before and after standard therapy through single-nucleus RNA and ATAC sequencing, whole-genome sequencing, and CODEX spatial proteomics to capture the evolution of the tumor microenvironment during progression following treatment. We found that the canonical neoplastic cell phenotypes of adult glioblastoma are insufficient to capture the range of tumor cell states in a pediatric cohort and observed differential tumor-myeloid interactions between malignant cell states. We identified key transcriptional regulators of pHGG cell states and did not observe the marked proneural to mesenchymal shift characteristic of adult glioblastoma. We showed that essential neuromodulators and the interferon response are upregulated post-therapy along with an increase in non-neoplastic oligodendrocytes. Throughin vitropharmacological perturbation, we demonstrated novel malignant cell-intrinsic targets. This multiomic atlas of longitudinal pHGG captures the key features of therapy response that support distinction from its adult counterpart and suggests therapeutic strategies which are targeted to pediatric gliomas.
PhyloForge: Unifying micro and macro evolution with comprehensive genomic signals
Authors: Wang Ya , Dong Wei , Liang Yufan , Lin Weiwei , Chen Fei
Published: March 2024

With the explosive growth of biological data, the dimensions of phylogenetic research have expanded to encompass various aspects, including the study of large-scale populations at the microevolutionary level and comparisons between different species or taxonomic units at the macroevolutionary level. Traditional phylogenetic tools often struggle to handle the diverse and complex data required for these different evolutionary scales. In response to this challenge, we introduce PhyloForge-a robust tool designed to seamlessly integrate the demands of both micro- and macro-evolution, comprehensively utilizing diverse phylogenomic signals, such as genes, SNPs, structural variations, as well as mitochondrial and chloroplast genomes. PhyloForge’s groundbreaking innovation lies in its capability to seamlessly integrate multiple phylogenomic signals, enabling unified analysis of multidimensional genomic data. This unique feature empowers researchers to gain a more comprehensive understanding of diverse aspects of biological evolution. PhyloForge not only provides highly customizable analysis tools for experienced researchers but also features an intuitively designed interface, facilitating effortless phylogenetic analysis for beginners. Extensive testing across various domains, including animals, plants, and fungi, attests to its broad applicability in the field of phylogenetics. In summary, the developmental background and innovative features of PhyloForge position it with significant potential in the era of large-scale genomics, offering a new perspective and toolset for a deeper understanding of the evolution of life.
Antisense transcription can induce expression memory via stable promoter repression
Authors: Mutzel Verena , Schwämmle Till , Oeverdieck Svearike , Librenjak Lucija , Boesen Benedikt , Bothe Melissa , Gjaltema Rutger AF , Dunkel Ilona , Noviello Gemma , Schulz Edda G
Published: March 2024

The capacity of cells to retain a memory of previous signals enables them to adopt unique cell fates and adjust to their surrounding environment. The underlying gene expression memory can arise from mutual repression of two genes, forming a toggle switch. Such mutual repression may occur at antisense loci, where two convergently oriented genes repress each other incis. Under which conditions antisense transcription can generate expression memory remains poorly understood. To address this question, we combine mathematical modeling, genomics and a synthetic biology approach. Through simulations we show that stable memory can emerge, if both genes in an antisense pair transcribe through the convergent promoter and induce a stable repressive chromatin state. Genome-wide analysis of nascent transcription further supports antisense-mediated promoter repression with promoter-overlapping antisense gene pairs exhibiting mutually exclusive expression. Through constructing a synthetic antisense locus in mouse embryonic stem cells (mESCs) we then show that such a locus architecture can indeed maintain a memory of a transient stimulus. Mutual repression and the capacity for memory formation are elevated, when mESCs differentiate, showing that epigenetic memory is a cell type-specific property. Our finding that stem cells adapt their ability to remember stimuli as they differentiate might help to elucidate how stemness is maintained.
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

Shigella 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

Background

Children 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.

Methods

We 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.

Results

Mother’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.

Conclusion

Results 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

SAMHD1 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.

IMPORTANCE

Antiviral 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

Campylobacter 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

The 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

Adeno-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.
Reconstructing charged particle track segments with a quantum-enhanced support vector machine
Authors: Duckett Philippa , Facini Gabriel , Jastrzebski Marcin , Malik Sarah , Scanlon Tim , Rettie Sébastien
Published: March 2024

Reconstructing the trajectories of charged particles from the collection of hits they leave in the detectors of collider experiments like those at the Large Hadron Collider (LHC) is a challenging combinatorics problem and computationally intensive. The tenfold increase in the delivered luminosity at the upgraded High Luminosity LHC will result in a very densely populated detector environment. The time taken by conventional techniques for reconstructing particle tracks scales worse than quadratically with track density. Accurately and efficiently assigning the collection of hits left in the tracking detector to the correct particle will be a computational bottleneck and has motivated studying possible alternative approaches. This paper presents a quantum-enhanced machine learning algorithm that uses a support vector machine (SVM) with a quantum-estimated kernel to classify a set of three hits (triplets) as either belonging to or not belonging to the same particle track. The performance of the algorithm is then compared to a fully classical SVM. The quantum algorithm shows an improvement in accuracy versus the classical algorithm. Model complexity metrics are used to hint at an explanation for favorable performance of the quantum kernel.

Published by the American Physical Society
2024
Photon and dilepton emission anisotropy for a magnetized quark-gluon plasma
Authors: Wang Xinyang , Shovkovy Igor A.
Published: March 2024

We study the higher-order anisotropy coefficients v4 and v6 in the photon and dilepton emission from a hot magnetized quark-gluon plasma. Together with the earlier predictions for v2, these results show a distinctive pattern of the anisotropy coefficients in several kinematic regimes. In the case of photon emission, nonzero coefficients vn (with even n) have opposite signs at small and large values of the transverse momentum (i.e., kT≲|eB| and kT≳|eB|, respectively). Additionally, the vn signs alternate with increasing n, and their approximate values decrease as 1/n2 in magnitude. The anisotropy of dilepton emission is well pronounced only at large transverse momenta and small invariant masses (i.e., when kT≳|eB| and M≲|eB|). The corresponding v4 and v6 coefficients are of the same magnitude and show a similar alternating sign pattern with increasing n as in the photon emission.

Published by the American Physical Society
2024
Signatures of vacuum birefringence in low-power flying focus pulses
Authors: Formanek Martin , Palastro John P. , Ramsey Dillon , Weber Stefan , Di Piazza Antonino
Published: March 2024

Vacuum birefringence produces a differential phase between orthogonally polarized components of a weak electromagnetic probe in the presence of a strong electromagnetic field. Despite representing a hallmark prediction of quantum electrodynamics, vacuum birefringence remains untested in pure light configurations due to the extremely large electromagnetic fields required for a detectable phase difference. Here, we exploit the programmable focal velocity and extended focal range of a flying focus laser pulse to substantially lower the laser power required for detection of vacuum birefringence. In the proposed scheme, a linearly polarized x-ray probe pulse counterpropagates with respect to a flying focus pulse, whose focus moves at the speed of light in the same direction as the x-ray probe. The peak intensity of the flying focus pulse overlaps the probe over millimeter-scale distances and induces a polarization ellipticity on the order of 10−10, which lies within the detection sensitivity of existing x-ray polarimeters.

Published by the American Physical Society
2024
Statistics of thermal gas pressure as a probe of cosmology and galaxy formation
Authors: Chen Ziyang , Jamieson Drew , Komatsu Eiichiro , Bose Sownak , Dolag Klaus , Hadzhiyska Boryana , Hernández-Aguayo César , Hernquist Lars , Kannan Rahul , Pakmor Rüdiger , Springel Volker
Published: March 2024

The statistics of thermal gas pressure are a new and promising probe of cosmology and astrophysics. The large-scale cross-correlation between galaxies and the thermal Sunyaev-Zeldovich effect gives the bias-weighted mean electron pressure, ⟨bhPe⟩. In this paper, we show that ⟨bhPe⟩ is sensitive to the amplitude of fluctuations in matter density, for example ⟨bhPe⟩∝(σ8Ωm0.81h0.67)3.14 at redshift z=0. We find that at z<0.5 the observed ⟨bhPe⟩ is smaller than that predicted by the state-of-the-art hydrodynamical simulations of galaxy formation, MillenniumTNG, by a factor of 0.93. This can be explained by a lower value of σ8 and Ωm, similar to the so-called “S8 tension” seen in the gravitational lensing effect, although the influence of astrophysics cannot be completely excluded. The difference between and MillenniumTNG at z<2 is small, indicating that the difference in the galaxy formation models used by these simulations has little impact on ⟨bhPe⟩ at this redshift range. At higher z, we find that both simulations are in a modest tension with the existing upper bounds on ⟨bhPe⟩. We also find a significant difference between these simulations there, which we attribute to a larger sensitivity to the galaxy formation models in the high redshift regime. Therefore, more precise measurements of ⟨bhPe⟩ at all redshifts will provide a new test of our understanding of cosmology and galaxy formation.

Published by the American Physical Society
2024
The barriers to advancing race equality in Scottish local authority employment
Authors: Hofmann Silvio
Published: March 2024

Purpose

This 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/approach

This 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.

Findings

The 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/value

The 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

Purpose

Family 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/approach

This paper is based on the systematic research.

Findings

While 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/implications

By 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 implications

Family 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 implications

Family 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/value

The 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

To 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

Objective

To 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 Setting

Secondary data on health expenditure were extracted from international and national agencies spanning the years 2000–2020.

Study Design

International 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 Methods

Health 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 Findings

We 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.

Conclusions

The 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

Seafood 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 Application

Recently, 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

Backgrounds

Acute anterior uveitis (AAU) is the most common extra‐musculoskeletal manifestation in axial spondyloarthritis (axSpA).

Objectives

The aim of the study is to evaluate the factors associated with AAU attacks in patients with axSpA during a 36‐month follow‐up period.

Methods

In 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.

Results

Overall, 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.

Conclusions

AAU 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.