bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccines for immunological defense against traumatic brain injury
Authors: Lintecum Kelly , Thumsi Abhirami , Dunn Kara , Druschel Lindsey , Chimene Sierra , Prieto David Flores , Simmons Amberlyn , Mantri Shivani , Esrafili Arezoo , Swaminathan Srivatsan J. , Trivedi Mytreyi , Manjre Shreya , Willingham Crystal , Kizeev Gabriele , Davila Alondra , Inamdar Sahil , Mangal Joslyn L. , Suresh Abhirami P. , Kasthuri Niveda M. , Jaggarapu Madan Mohan Chandra Sekhar , Appel Nicole , Khodaei Taravat , Ng Nathan D. , Sundem Alison , Pathak Sanmoy , Bjorklund George , Balmer Timothy , Newbern Jason , Capadona Jeffrey , Stabenfeldt Sarah E. , Acharya Abhinav P.
Published: December 2024

Traumatic brain injury (TBI) and subsequent neurodegeneration is partially driven by chronic inflammation both locally and systemically. Yet, current clinical intervention strategies do not mitigate inflammation sequalae necessitating the development of innovative approaches to reduce inflammation and minimize deleterious effects of TBI. Herein, a subcutaneous formulation based on polymer of alpha-ketoglutarate (paKG) delivering glycolytic inhibitor PFK15 (PFKFB3 inhibitor, a rate limiting step in glycolysis), alpha-ketoglutarate (to fuel Krebs cycle) and peptide antigen from myelin proteolipid protein (PLP139-151) was utilized as the prophylactic immunosuppressive formulation in a mouse model of TBI.In vitro,the paKG(PFK15+PLP) vaccine formulation stimulated proliferation of immunosuppressive regulatory T cells and induced generation of T helper-2 cells. When given subcutaneously in the periphery to two weeks prior to mice sustaining a TBI, the active vaccine formulation increased frequency of immunosuppressive macrophages and dendritic cells in the periphery and the brain at day 7 post- TBI and by 28 days post-TBI enhanced PLP-specific immunosuppressive cells infiltrated the brain. While immunohistology measurements of neuroinflammation were not altered 28 days post-TBI, the vaccine formulation improved motor function and enhanced autophagy mediated genes in a spatial manner in the brain. Overall, these data suggest that the TBI vaccine formulation successfully induced an anti-inflammatory profile and decreased TBI-associated inflammation.

Teaser

In this study, a vaccine formulation was generated to develop central nervous specific immunosuppressive responses for TBI.
Perception of Temperature Even in the Absence of Actual Change is Sufficient to Drive Transgenerational Epigenetic Inheritance
Authors: Teichman Guy , Sela Mor , Ewe Chee Kiang , Rieger Itai , Anava Sarit , Mor Yael , Szanto Peter , Meyer David H , Doron Hila , Shachar Or , Pechuk Vladyslava , Gingold Hila , Oren-Suissa Meital , McGee Matthew , Shapira Michael , Schumacher Bjorn , Rechavi Oded
Published: December 2024

Can processes occurring in one individuals nervous system influence the physiology of the descendants? Here we explored the provocative hypothesis that parents sensation or perception of environmental cues can influence their offspring, extending across many subsequent generations. We show that in Caenorhabditis elegans, temperature perception on its own can induce transgenerational changes in RNAi factors, small RNAs, and the genes that they regulate. Moreover, we identified secreted factors that enable a pair of thermosensory neurons (AFD) to communicate with the germline and trace the path of the epigenetic signal. We further modeled the process mathematically and validated the new predictions generated by the model experimentally. Hence, our results demonstrate that sensory perception is sufficient to trigger small RNA-mediated heritable gene expression memory.
High-throughput synapse profiling reveals cell-type-specific spatial configurations in the fly brain
Authors: Wu Hongyang , Maekawa Yoh , Eno Sayaka , Kondo Shu , Yamagata Nobuhiro , Tanimoto Hiromu
Published: December 2024

Characterization of intracellular synapse heterogeneity aides to understand the intricate computational logic of neuronal circuits. Despite recent advances in connectomics, the spatial patterns of synapses and their inter-individual variability remain largely unknown. Using directed split-GFP reconstitution, we achieved visualization of endogenous Bruchpilot (Brp) proteins, the presynaptic active zone (AZ) scaffold, in a cell-type-specific manner. By developing a high-throughput quantification pipeline, we profiled AZ structures in identified neurons of the mushroom body circuit, where intracellular synaptic pattern is crucial due to its compartmentalized connectivity. Quantitative characterization of the pattern of Brp clusters across multiple individuals revealed cell-type-dependent synapse heterogeneity and stereotypy. Furthermore, we discovered previously unidentified sub-compartmental synapse configuration and its regulation by cAMP signaling. These results of synapse profiling uncovered multi-layered organizations of AZs, ranging from neighboring synapses to consistent patterns across individuals.

Teaser

High-throughput profiling of single active zones revealed previously unidentified multi-layered synaptic organizations.
Octopamine signals coordinate the spatial pattern of presynaptic machineries within individualDrosophilamushroom body neurons
Authors: Wu Hongyang , Eno Sayaka , Jinnai Kyoko , Maekawa Yoh , Saito Kokoro , Abe Ayako , Williams Darren W , Yamagata Nobuhiro , Kondo Shu , Tanimoto Hiromu
Published: December 2024

Neurons need to adjust synaptic output according to the targets. However, the target-specific synaptic structures within individual neurons in the central nervous system remains unresolved. Applying the CRISPR/Cas9-mediated split-GFP tagging, we visualized the endogenous active zone scaffold protein, Bruchpilot (Brp), in specific cells. This technology enabled the spatial characterization of presynaptic machineries only within the Kenyon cells (KCs) of theDrosophilamushroom bodies. We found the patterned accumulation of Brp among the compartments of axon terminals, where a KC synapses onto different postsynaptic neurons. Mechanistically, the localized octopaminergic modulation along γ KC terminals regulate this compartmental Brp heterogeneity via Octβ2R and cAMP signaling. We further found that acute food deprivation reorganizes this spatial pattern in an octopamine-dependent manner. Such coordinated regulation of local synaptic machineries thus explains how the mushroom bodies integrate changing physiological states. This subcellular information processing represents an elegant solution to expand computational capacity of the circuit.
Diagnostic and prognostic value of alpha-synuclein seed amplification assay in Parkinson’s disease: a longitudinal cohort study
Authors: Orrú Christina D , Vaughan David P , Vijiaratnam Nirosen , Real Raquel , Carrasco Alejandro Martinez , Fumi Riona , Jensen Marte Theilmann , Hodgson Megan , Girges Christine , Gil-Martinez Ana-Luisa , Stafford Eleanor J. , Wu Lesley , Groveman Bradley R , Hughson Andrew G , Ansorge Olaf , Quaegebeur Annelies , Allinson Kieren SJ , Warner Thomas T , Jaunmuktane Zane , Misbahuddin Anjum , Leigh P Nigel , Ghosh Boyd CP , Bhatia Kailash P , Church Alistair , Kobylecki Christopher , Hu Michele TM , Rowe James B , Foltynie Thomas , Morris Huw R , Caughey Byron , Jabbari Edwin
Published: December 2024

Background

Alpha-synuclein seed amplification assay (a-syn SAA) has been proposed to be a diagnostic biomarker for Parkinson’s disease (PD). Here, we have explored the diagnostic and prognostic value of cerebrospinal fluid (CSF) a-syn SAA status and seeding kinetics in PD.

Methods

Baseline CSF a-syn SAA data and longitudinal clinical data were collected and analysed between 1stJanuary 2010 and 1stApril 2022 for the Parkinson’s Progression Markers Initiative (PPMI) and UK parkinsonism cohorts respectively. We calculated the sensitivity and specificity of a-syn SAA in PD and controls, used linear regression to analyse a-syn SAA positive vs. negative group comparisons, and used time-to-event analyses to assess the ability of a-syn SAA seeding kinetic measures to predict clinical decline in PD.

Findings

We studied 1,402 participants: publicly available data from the PPMI cohort, n=1275 (PD, n=1,036; controls, n=239); newly generated data from the UK parkinsonism cohort, n=127 (PD, n=66; progressive supranuclear palsy (PSP), n=52; controls n=9). Over 2-5 years of follow-up, the sensitivity of a-syn SAA in PD was 87.7% and the specificity in controls was 91.9%. A-syn SAA was positive in 8/52 (15.4%) PSP samples with distinct ‘low and slow’ kinetics. A-syn SAA negative LRRK2-PD participants (n=57) had an older mean (SD) age at symptom onset (63.0 (7.6) vs. 55.4 (9.9) years) and higher mean (SD) baseline serum neurofilament light chain levels (20.4 (13.2) vs. 13.8 (8.6) pg/ml), p<0.05, vs. a-syn SAA positive LRRK2-PD participants (n=110). The baseline seeding kinetic measure, time to threshold, predicted cognitive decline in PD, defined as MoCA ≤21 (HR 2.51, 95% CI 1.50-4.20, p=0.001).

Interpretation

In PD, a-syn SAA may have value as a diagnostic and prognostic biomarker in clinical practice and as a stratification tool in clinical trials. Furthermore, we have highlighted the presence of pathological heterogeneity in LRRK2-PD.

Funding

Medical Research Council, PSP Association.
High-throughput discovery and deep characterization of cyclin-CDK docking motifs
Authors: Örd Mihkel , Winters Matthew J. , Subbanna Mythili S. , de Martin Garrido Natalia , Cushing Victoria I. , Kliche Johanna , Benz Caroline , Ivarsson Ylva , Greber Basil J. , Pryciak Peter M. , Davey Norman E.
Published: December 2024

Cyclin-CDKs are master regulators of cell division. In addition to directly activating the CDK, the cyclin subunit regulates CDK specificity by binding short peptide “docking” motifs in CDK substrates. Here, we measure the relative binding strength of ∼100,000 peptides to 11 human cyclins from five cyclin families (D, E, A, B and F). Using a quantitative intracellular binding assay and large-scale tiled peptide screening, we identified a range of non-canonical binders that unveil a broader than anticipated repertoire of cyclin docking motif types. Structural and saturation mutagenesis studies revealed distinct binding modes and sequence features that govern motif recognition, binding strength, and cyclin preference. Docking motifs vary from highly selective to pan-cyclin, thereby fine-tuning the timing of CDK phosphorylation during cell cycle progression. Overall, these findings provide an unprecedented depth of understanding about the rules encoding specificity and affinity within a group of related but distinct protein domains.
In and out of replication stress: PCNA/RPA1-based dynamics of fork stalling and restart in the same cell
Authors: Dyankova-Danovska Teodora , Uzunova Sonya , Danovski Georgi , Stamatov Rumen , Kanev Petar-Bogomil , Atemin Aleksandar , Ivanova Aneliya , Stoynov Stoyno
Published: December 2024

Replication forks encounter various impediments which induce fork stalling and threaten genome stability, yet the precise dynamics of fork stalling and restart at the single-cell level remain elusive. Herein, we devise a live-cell microscopy-based approach to follow hydroxyurea-induced fork stalling and subsequent restart at 30-s resolution. We measure two distinct processes during fork stalling. One is rapid PCNA removal, which reflects the drop in DNA synthesis. The other is gradual RPA1 accumulation on up to 2400 nt of ssDNA per fork despite an active intra-S checkpoint. Restoring the nucleotide pool enables prompt restart without post-replicative ssDNA and a smooth cell cycle progression. ATR, but not ATM inhibition, accelerates hydroxyurea-induced RPA1 accumulation nine-fold, leading to RPA1 exhaustion within 20 min. Fork restart under ATR inhibition led to the persistence of ∼600 nt ssDNA per fork after S-phase, which reached 2500 nt under ATR/ATM co-inhibition, with both scenarios leading to mitotic catastrophe. MRE11 inhibition had no effect on PCNA/RPA1 dynamics regardless of ATR activity. E3 ligase RAD18 was recruited at stalled replication forks in parallel to PCNA removal. Our results shed light on fork dynamics during nucleotide depletion and provide a valuable tool for interrogating the effects of replication stress-inducing anti-cancer agents.
Microglial cathepsin B promotes neuronal efferocytosis during brain development
Authors: Silva Nicholas J , Anderson Sarah , Mula Supriya A , Escoubas Caroline C , Nakajo Haruna , Molofsky Anna V
Published: December 2024

Half of all newborn neurons in the developing brain are removed via efferocytosis - the phagocytic clearance of apoptotic cells. Microglia are brain-resident professional phagocytes that play important roles in neural circuit development including as primary effectors of efferocytosis. While the mechanisms through which microglia recognize potential phagocytic cargo are widely studied, the lysosomal mechanisms that are necessary for efficient digestion are less well defined. Here we show that the lysosomal protease cathepsin B promotes microglial efferocytosis of neurons and restricts the accumulation of apoptotic cells during brain development. We show that cathepsin B is microglia-specific and enriched in brain regions where neuronal turnover is high in both zebrafish and mouse. Myeloid-specific cathepsin B knockdown in zebrafish led to dysmorphic microglia containing undigested dead cells, as well as an accumulation of dead cells in surrounding tissue. These effects where phenocopied in mice globally deficient forCtsbusing markers for apoptosis. We also observed behavioral impairments in both models. Live imaging studies in zebrafish revealed deficits in phagolysosomal fusion and acidification, and live imaging of cultured mouse microglia reveal delayed phagocytosis consistent with impairments in digestion and resolution of phagocytosis rather than initial uptake. These data reveal a novel role for microglial cathepsin B in mediating neuronal efferocytosis during typical brain development.
Extracellular HDAC6 ZnF UBP domain enhances podosome-mediated neuronal migration
Authors: Qureshi Tazeen , Desale Smita Eknath , Sonawane Shweta Kishor , Balmik Abhishek Ankur , Chidambaram Hariharakrishnan , Chinnathambi Subashchandrabose
Published: December 2024

The increasing prevalence of Alzheimer’s disease demands research into therapeutic strategies that go beyond Amyloid and Tau. Synaptic loss, neuritic loss, and microtubule destabilization due to misfolded Tau and dysfunctional signalling in the AD-affected neuron, all point toward understanding and targeting cytoskeletal dysregulation in AD. Here we present, an extensive study on the novel role of the ZnF UBP (Zinc Finger Ubiquitin Binding Protein) domain of HDAC6 (Histone Deacetylase 6) in actin remodelling in neurons. We have demonstrated this function through immunofluorescence colocalization analysis in actin-rich podosome structures. We have found that this HDAC6 domain induces increased localization of the actin polymerization proteins, Arp2 and WASP and the adaptor protein TKS5 in the podosome structures. We have also extended our work to understand the potential of this domain in enhancing the podosome-mediated migration of neuronal cells. It was thus established that HDAC6 ZnF UBP induces increased association of cytoskeletal proteins within the podosomes, conferring enhanced migration potential to neurons and presenting an interesting strategy to improve neuronal health.
Schmallenberg virus non-structural proteins NSs and NSm are not essential for experimental infection ofCulicoides sonorensisbiting midges
Authors: Wernike Kerstin , Vasic Ana , Amler Susanne , Sick Franziska , Răileanu Cristian , Dähn Oliver , Kampen Helge , Silaghi Cornelia , Beer Martin
Published: December 2024

The teratogenic orthobunyavirus Schmallenberg virus (SBV) is transmitted between its mammalian hosts byCulicoidesbiting midges. The genome of circulating SBV, i.e. variants present in viraemic ruminants or insect vectors, is very stable, while variants found in malformed ruminant foetuses display a high genetic variability. It was suggested that foetal infection provides an environment that favours viral mutations that enable immune escape in the unborn, but at the costs of limiting the ability of the virus to spread further. To investigate infection and dissemination rates of different SBV variants in the insect vectors, we fed laboratory-rearedCulicoides sonorensiswith blood containing the prototype strain BH80/11-4 from a viraemic cow or strain D281/12, which was isolated from the brain of a sheep foetus and harbours multiple mutations in all three genome segments. Further, virus variants lacking NSs, NSm or both non-structural proteins were included. Six days after feeding, virus replication was found in about 2% of the midges exposed to wild-type strain BH80/11-4. The absence of the non-structural proteins had no obvious effect on the oral susceptibility to virus infection, as 2.78% of the midges fed with the NSs-deletion mutant displayed after six days viral loads higher than the respective day-0-group, 1.92% of the midges exposed to the NSm-deletion mutant and 1.55% of midges exposed to the NSs/NSm-deletion mutant. In contrast, strain D281/12 did not replicate at all in the midges, supporting the assumption that SBV variants arising in infected foetuses are unable to enter the normal insect-mammalian host cycle.

Importance

Biting midges are responsible for the transmission of Schmallenberg virus (SBV), a pathogen of veterinary importance that primarily infects ruminants. Although SBV has been extensively studied in the mammalian host, the virus-intrinsic factors allowing infection of, and replication in, biting midges are largely unknown. Therefore, we infected laboratory-rearedCulicoides sonorensismidges with SBV variants by feeding them with virus-containing blood. The SBV variants differed in their genome composition, as we used the prototype wild-type strain, a strain with multiple mutations that was isolated from the brain of a malformed foetus, and recombinants lacking either NSs or NSm or both of these non-structural proteins. While the non-structural proteins had no obvious effect, the variant from the malformed foetus did not replicate at all, indicating that virus variants with characteristic genomic mutations present in foetuses lose their ability to infect the insect vector and will be excluded from the natural transmission cycle.
The histone demethylase KDM5 has insulator activity in the brain
Authors: Yheskel Matanel , Castiglione Melissa A. , Kelly Richard D. , Sidoli Simone , Secombe Julie
Published: December 2024

KDM5 family proteins are best known for their demethylation of the promoter proximal chromatin mark H3K4me3. KDM5-regulated transcription is critical in the brain, with variants in the X-linked paralogKDM5Ccausing the intellectual disability (ID) disorder Claes-Jensen syndrome. Although the demethylase activity of KDM5C is known to be important for neuronal function, the contribution of non-enzymatic activities remain less characterized. We therefore usedDrosophilato model the ID variantKdm5L854F, which disrupts a C5HC2 zinc finger adjacent to the enzymatic JmjC domain.Kdm5L854Fcauses similar transcriptional changes in the brain to a demethylase dead strain,Kdm5J1310C*, despite having little effect on enzymatic activity. KDM5L854Fis also distinct from KDM5J1310C* in its reduced interactions with insulator proteins and enhancement of position effect variegation. Instead, the common transcriptional deficits likely result from both the JmjC and C5HC2 domains driving proper genomic organization through their activity in promoting proper loop architecture.
Gut MicrobiotAware: how much do we know about gut microbiota? An international questionnaire
Authors: Garcia-Gutierrez Enriqueta , Arbulu Sara , Oliver Charlotte , Kumar Sandeep , Dam Sarita A. , Jakobi Babette , Pennone Vincenzo , Hoffmann Sarda Fabiana A. , Mukherjee Arghya , Cotter Paul D.
Published: December 2024

Over the past two decades, our understanding of human gut microbiota composition and function has grown significantly. The surge in studies and data has unveiled the profound influence of gut microbiota on host nutrition, health, and behavior, bridging biology, medicine, and ecology. The dynamic interaction between daily choices, life events, and gut microbiota composition makes it a fascinating subject for scientists to communicate to diverse audiences. Effective scientific communication involves adapting the delivery of knowledge to different audiences, using precise language in academic settings and accessible concepts in public forums like science festivals or social media. With the growing interest in gut microbiota beyond academic circles, there is an increased risk of disseminating information lacking scientific rigor. This study aims to assess the general public’s knowledge about gut microbiota and evaluate healthcare professionals’ understanding of its links to various health conditions, ultimately informing better communication strategies for both groups.
The Effects of Heat Stress on the Ovary, Follicles and Oocytes: A Systematic Review
Authors: Zhou Luhan T. , Gokyer Dilan , Madkins Krystal , Beestrum Molly , Horton Daniel E. , Duncan Francesca E. , Babayev Elnur
Published: December 2024

Climate change is driving significant environmental changes with profound implications for human health, including fertility. While the detrimental effects of heat on spermatogenesis are well-documented, the impact of elevated temperatures on ovaries and female fertility remains less explored. This review systematically examines the literature on heat stress (HS) effects on mammalian ovaries, follicles, and oocytes. Evidence from mammalian models indicates that HS significantly impairs ovarian function, disrupting hormone profiles, reducing ovarian size and weight, altering histology, decreasing granulosa cell viability, and compromising oocyte quality. Efforts to develop strategies and substances to mitigate these adverse effects are ongoing, but further research into the underlying mechanisms is urgently needed.

Summary Sentence

This systematic review summarizes the evidence on the adverse effects of heat stress on the mammalian oocyte and ovary
Effects of hybridization and gene flow on gene co-expression networks
Authors: Rogini Runghen , Bolnick Daniel I.
Published: December 2024

Gene co-expression networks are a widely used tool for summarizing transcriptomic variation between individuals, and for inferring the transcriptional regulatory pathways that mediate genotype-phenotype relationships. However, these co-expression networks must be interpreted with caution, as they can arise from multiple processes. Here, we show that hybridization and gene flow between populations can greatly modify co-expression networks. Admixture between populations produces correlated expression between genes experiencing linkage disequilibrium. This correlated expression does not reflect functional relationships between genes, but rather depends on migration rates and physical linkage on chromosomes. Given the prevalence of gene flow between divergent populations in nature, these introgression effects likely represent a significant force in network evolution, even in populations where hybridization is historical rather than contemporary. These findings emphasize the critical importance of considering both evolutionary history and genomic architecture when analyzing gene co-expression networks in natural populations.
D1 is a novel enhancer blocker protein that functions via multiple AT-rich simple sequence repeats
Authors: Phanindhar Kundurthi , Athar Fathima , Mishra Rakesh K
Published: December 2024

Simple sequence repeats (SSRs) are tandem repeats of 1-6 bp DNA motifs with a size of at least 12 bp, constitute a significant portion of, especially, higher eukaryotes. Earlier studies have shown that length-enriched repeats have various cis-regulatory activities, however, the mechanism of these activities is not well understood. To better understand their function, here we identify proteins that bind to the repeats using protein pull-down followed by LC-MS/MS. We find that many repeats have multiple repeat-binding proteins and that some of these proteins bind to multiple repeats. We report that D1, an AT-hook domain containing protein, binds to multiple repeats, viz., AAT14, AAAT10, and AAAAT8. As repeats are known to function as enhancer blockers inDrosophila, we developed a new enhancer blocker assay that uses visible wing phenotype as enhancer blocking activity and allows use of classicDrosophilagenetic approach to explore modifiers of this activity at thevestigiallocus. Using this assay, we show that the repeats AAT14, AAAT10, AAAAT8and AATAT9function as enhancer blockers via the protein D1. Our findings make the enhancer blocking regulatory function of a DNA sequence of interest, accessible to the powerful genetics ofDrosophilaand, thereby, presents effective approach to understand the mechanism of such chromatin domain boundary elements.
Immortalization of mesenchymal stromal cells by hTERT does not affect the functional properties of secreted extracellular vesicles
Authors: Brancolini Alessia , Bobbili Madhusudhan Reddy , Pultar Marianne , Mazidi Zahra , Wieser Matthias , Gamauf Johanna , Roefs Marieke Theodora , Corso Giulia , Nivarthi Harini , Paredes Maria Belen Arteaga , Bettelheim Dieter , Arcalis Elsa , Dmitry Sivun , Jacak Jaroslaw , Gerner Iris , Hackl Matthias , Grillari Johannes , Grillari-Voglauer Regina
Published: December 2024

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as promising and safe therapeutic agents, however, donor heterogeneities, limited replicative life span and changes in the cellular phenotype throughout in vitro cultivation remain major hurdles for scalable EV production. For these reasons, this study aims to investigate the use of hTERT immortalized (‘telomerized’) MSCs as a potential source for efficient, standardized, reliable MSC-EVs production by comparing parental primary to their telomerized MSC counterparts. We observed that hTERT expression does not affect cell morphology or cellular doubling time, while ensuring unlimited, stable in vitro propagation. In addition, telomerized WJ-MSCs maintained the canonical expression profile of surface markers and the tri-lineage differentiation potential of their primary counterparts. In terms of EV characteristics, the immortalization by hTERT expression did not affect size, number, cargo composition or biological activity regarding anti-inflammatory, anti-fibrotic and wound healing properties in vitro. In summary, the use of hTERT to immortalize MSCs leads to the creation of cell lines that continuously produce MSC-EVs without altering any key functionalities of the cells or resulting EVs. This suggests that telomerization of human cells from single donors is a promising strategy for generating cell factories that can produce EVs in standardized conditions and at scale and with standardization.
Forcing the code: tension modulates signaling to drive morphogenesis and malignancy
Authors: Narain Radhika , Muncie-Vasic Jonathon M. , Weaver Valerie M.
Published: December 2024

Development and disease are regulated by the interplay between genetics and the signaling pathways stimulated by morphogens, growth factors, and cytokines. Experimental data highlight the importance of mechanical force in regulating embryonic development, tissue morphogenesis, and malignancy. Force not only sculpts tissue movements to drive embryogenesis and morphogenesis but also modifies the context of biochemical signaling and gene expression to regulate cell and tissue fate. Not surprisingly, experiments have demonstrated that perturbations in cell tension drive malignancy and metastasis by altering biochemical signaling and gene expression through modifications in cytoskeletal tension, transmembrane receptor structure and function, and organelle phenotype that enhance cell growth and survival, alter metabolism, and foster cell migration and invasion. At the tissue level, tumor-associated forces disrupt cell–cell adhesions to perturb tissue organization, compromise vascular integrity to induce hypoxia, and interfere with antitumor immunity to foster metastasis and treatment resistance. Exciting new approaches now exist with which to clarify the relationship between mechanotransduction, biochemical signaling, and gene expression in development and disease. Indeed, gaining insight into these interactions is essential to unravel molecular mechanisms that regulate development and clarify the molecular basis of cancer.
Neutrinos in the flavor-dependent
U(1)F
model
Authors: Yang Jin-Lei , Li Jie
Published: December 2024

The neutrino oscillation experiments provide definitive evidence of new physics beyond the Standard Model, and the neutrino mass-squared differences and flavor mixing have been precisely measured. This study examines the neutrino sector within the flavor-dependent U(1)F model, where the unique fermion sector can simultaneously address both the flavor mixing puzzle and the mass hierarchy puzzle. It is found that the lightest neutrino is naturally massless in this model, and the predicted neutrino mass-squared differences, flavor mixing angles, and Dirac CP phase agree well with the experimental measurements. Additionally, the effects of the Dirac CP phase and Majorana CP phase on the theoretical predictions of the neutrino transition magnetic dipole moments are analyzed.

Published by the American Physical Society
2024
Thermodynamics of heavy quarkonium in the spinning black hole background
Authors: Zhu Zhou-Run , Wang Sheng , Chen Xun , Chen Jun-Xia , Hou Defu
Published: December 2024

In this study, we explore the thermodynamics of heavy quarkonium within the context of a spinning black hole background. Specifically, we analyze the impact of angular momentum on various thermodynamic properties of heavy quarkonium, including interquark distance, free energy, binding energy, entropy, entropic force, and internal energy, based on the thermodynamic relationships. Our results demonstrate that angular momentum diminishes the maximum interquark distance, thereby facilitating quarkonium dissociation. Furthermore, we note that angular momentum suppresses free energy. The analysis of binding energy reveals that angular momentum enhances the dissociation of mesons into free quarks and antiquarks. Additionally, our findings indicate that angular momentum augments entropy and entropic force, thereby accelerating quarkonium dissociation. Angular momentum also increases internal energy at extended interquark distances. Lastly, we observe that the effects of angular momentum on quarkonium are more significant when the axis of the quark pair QQ¯ is perpendicular to the direction of angular momentum.

Published by the American Physical Society
2024
Benchmarking Bosonic Modes for Quantum Information with Randomized Displacements
Authors: Valahu Christophe H. , Navickas Tomas , Biercuk Michael J. , Tan Ting Rei
Published: December 2024

Bosonic modes are prevalent in all aspects of quantum information processing. However, existing tools for characterizing the quality, stability, and noise properties of bosonic modes are limited, especially in a driven setting. Here, we propose, demonstrate, and analyze a randomized bosonic benchmarking (RBB) protocol that uses randomized displacements of the bosonic modes in phase space to determine their quality. We investigate the impact of common analytical error models, such as heating and dephasing, on the distribution of outcomes over randomized displacement trajectories in phase space. We show that analyzing the distinctive behavior of the mean and variance of this distribution—describable as a gamma distribution—enables identification of error processes, and quantitative extraction of error rates and correlations using a minimal number of measurements. We experimentally validate the analytical models by injecting engineered noise into the motional mode of a trapped-ion system and performing the RBB protocol, showing good agreement between experiment and theory. Finally, we investigate the intrinsic error properties in our system, identifying the presence of highly correlated dephasing noise as the dominant process.

Published by the American Physical Society
2024
The development logic of capital under socialism with
Chinese characteristics
Authors: Fan Xin , Song Xiaoyu
Published: December 2024

Purpose

Regulating and guiding the sound development of capital under a socialist
system is not only a significant theoretical innovation rooted in Chinese
practice by the Communist Party of China (CPC) but also a major practical
exploration for the smooth progression of the party and the nation’s
modernization endeavors.

Design/methodology/approach

Adopting an analytical framework that unifies theoretical, historical and
practical logic, this paper explores the rationality of capital’s
existence under a socialist system based on the notion that capital is a
materialized production relationship. It also examines the staged evolution
of capital theory under socialism, highlighting the great leap forward
realized by the capital theory of socialism with Chinese
characteristics.

Findings

With the CPC Central Committee’s deepening understanding of the
capital patterns in the socialist system, capital-related policies have
undergone a developmental journey through several stages – from the
negation and elimination of capital to the support and operation of capital
and finally to the stage of regulating and guiding capital. This reflects
the reciprocal and complementary relationship between capital theory and
capital policy.

Originality/value

In response to issues such as the disorderly expansion of capital in the new
development stage, it is imperative to actively promote a practical pathway
safeguarded by the adherence to Party leadership, guided by the capital
theory of socialism with Chinese characteristics and targeted toward common
prosperity.
Development of web based data-driven recommendation system for house rental via hierarchical fuzzy axiomatic design
Authors: Şenyüzlüler Filiz , Baykasoglu Adil
Published: December 2024

Purpose

In the real estate business, identifying the ideal property for a user poses a difficult task due to the many factors involved in the decision-making process. Moreover, users often struggle to find platforms that facilitate effective communication of their preferences. To tackle this issue, a web-based data-driven recommendation system has been devised for the real estate business.

Design/methodology/approach

The process of identifying the most suitable rental property for a user hinges greatly on how the user prioritizes each criterion and the analysis of unstructured data. In this research, a novel recommendation system for house rentals is developed by utilizing the Weighted Hierarchical Fuzzy Axiomatic Design (WFAD) approach. Techniques for extracting pertinent information from unstructured house descriptions are employed. The user’s preferences are captured through an interactive web application equipped with a map feature to highlight key locations.

Findings

Data on various available rental properties are gathered using web scraping techniques. The efficacy of the proposed rental house recommendation system is demonstrated through multiple case studies. It is observed that the developed system provides more informed and reliable decisions.

Originality/value

First time in the related literature, we applied the weighted fuzzy axiomatic design procedure (WFAD) to the product recommendation problem and developed a comprehensive web-based system for recommending rental houses based on it in the real estate business.
Evaluation of productivity in laser sintering by measure and assessment of geometrical complexity
Authors: Haefele Tobias , Schneberger Jan-Henrik , Buchholz Soeren , Vielhaber Michael , Griebsch Juergen
Published: December 2024

Purpose

In additive manufacturing (AM), “complexity for free” is often cited as a major technological benefit. This generalized view has been found inaccurate by several authors dealing with the evaluation of part complexity. However, the term “complexity” is not defined uniformly. The reasons for this are the various AM processes and different evaluation factors used by the respective authors. This is critical because build time heavily depends on the impact of complexity on the additive process through the processing tool (point-to-point-, line- and mask-based) defining competitiveness. This study aims to define appropriate complexity indicators and evaluate the impact on productivity of PBF-LB/P (laser sintering).

Design/methodology/approach

An assessment methodology for geometric complexity is developed for point-to-point-based processes using the PBF-LB/P process. First, an overview of part characteristics and their interrelationships with the generation process is provided. In this way, relevant factors, e.g. part volume and perimeter length, are identified. Subsequently, these are used to create a metric to select and manufacture test samples to quantify the impact on build time.

Findings

The results indicate a strong impact of geometrical complexity on build time and build-up rate. Consequently, optimizing the geometry in the early design stage and adjusting process parameters during production planning allow to influence the build-up rate.

Originality/value

This paper demonstrates the effects of geometric complexity using manufacturing jobs. As a result, the suitability of existing methods and KPIs is shown to be insufficient. Hence, meaningful indicators for laser sintering, such as contour length vs hatch length, contour length vs part volume and number of hatches vs part volume, are defined and verified.
The New Politics of Public Inquiries
Authors: Flinders Matthew
Published: December 2024

This article argues that it is possible to identify a ‘new’ politics of public inquiries. A sizable seam of scholarship and parliamentary discussion has for at least a century bemoaned the limited independence of public inquiries. The ‘old’ politics of public inquiries has traditionally been defined by a largely internalised and administrative focus on the capacity of ministers to control the terms of reference, appoint the chair, control the resource framework, deflect findings and ignore recommendations, etc. The great value of the September 2024 report by the Statutory Inquiries Committee in the House of Lords is that a bridge can be seen to be built between the ‘old’ politics of public inquiries and a ‘new’ politics which emphasises ‘range and variation’ in the design of inquiry processes, and defines social healing and collective catharsis as core inquiry functions alongside the traditional roles of blame allocation and policy learning.
Modelling inclusive education. The Didactic Model for Inclusive Teaching and Learning as a heuristic for inclusion research and teacher education
Authors: Frohn Julia
Published: December 2024

Research on inclusive education has gained major importance over the last decade. However, in the English‐speaking discourse, empirical studies on inclusive teaching and learning often lack connections to existing educational theories that focus on the interrelation of teachers, learners and content as the three focal points of teaching and learning in a greater societal context. This corresponds with a lack of comprehensive models of inclusive education for teacher education. This theoretical paper therefore presents the ‘Didactic Model for Inclusive Teaching and Learning’ (DIMILL), developed in an interdisciplinary research team as a theoretical and practical framework for inclusion research and teacher education. Following an introduction on the necessity of modelling inclusive education in school settings, the German tradition of ‘didactics’ will be contextualized in the international field, pointing out its potential for educational theory and teacher education. Then, individual parts of DIMILL are introduced and related to one another. Finally, modes of practical implementation as well as possible implications for educational research and inclusive teacher education will be discussed.
Catherine Hutton's Travel Diary (1779)
Authors: Baula Anna , Philp Mark
Published: December 2024

The only diary the author Catherine Hutton (1756–1846) is known to have kept is her travel diary, written in 1779 at the age of 23, in which she describes staying with various members of her extended family and friends while travelling around the Midlands. Her trip starts from her home in Birmingham and takes her through much of Derbyshire, with visits to Leicester and Nottingham towards the end of the journey. The diary offers a rich and vivid account of the sociability of a female member of the middling class, and of the trials that could involve, and sheds light both on Hutton's earlier life, and on the conventions and social mores of the time. The introduction contextualizes the journal and points to some of the challenges in exactly how it might be read.
Income smoothing in banks: Obfuscation or information?
Authors: Narayanamoorthy Ganapathi S. , Wheeler P. Barrett
Published: December 2024

Discretionary income smoothing has been argued to increase bank opacity and degrade financial system stability by making banks more difficult to monitor. However, no direct empirical association between discretionary smoothing and opacity has been established to date. We argue that smoothing could reflect either the opportunistic exercise of discretion that disconnects loan loss provisions (LLPs) from changes in underlying credit quality, consistent with smoothing increasing opacity, or an informative exercise of discretion to communicate forward‐looking information about loan losses. We examine the association between discretionary smoothing and the informativeness of LLPs for a sample of banks from 1994 to 2019 and find that discretionary smoothing is, on average, associated with more informative LLPs. However, this association is nuanced, with cross‐sectional differences and changes over time. We find evidence that an intervention by the SEC into bank LLP practices in the late 1990s curbed opportunistic smoothing via provisioning for homogeneous loans. Subsequently, smoothing is associated with more informative provisions, including for banks with both more homogeneous and more heterogeneous loan portfolios. Our findings are inconsistent with the notion that smoothing may be associated with greater opacity.
Stable prevalence of overweight but increasing levels of obesity in adolescents in surveys of 42982 children in China 2010 to 2020
Authors: Li Chengyue , Zhou Zhidong , Cui Haiwen
Published: December 2024

Aim

Excessive weight gain in childhood has been associated with poor health outcomes throughout life span and has a strong tracking effect in adulthood. This study aimed to investigate trends in the prevalence of overweight, obesity and severe obesity among Chinese children from 2010 to 2020.

Methods

A total of 42 982 Chinese children aged 2–18 years were included in the Chinese Family Panel Studies carried out every 2 years from 2010 to 2020. Height and mass were reported by them or by their guardians and body mass index was calculated. The prevalence was estimated according to the International Obesity Task Force cut‐offs.

Results

There was no significant trend in the prevalence of overweight. The prevalence of obesity and severe obesity for the total population decreased from 8.3% and 3.7% in 2010 to 7.1% and 2.6% in 2020, respectively (p < 0.001). However, these decreases were attributed mostly to children aged 2–6 years and the prevalence increased among children aged 13–18 years. Male, rural residential area and younger age were risk factors for overweight and obesity.

Conclusion

A decrease in the prevalence of excessive weight was a positive finding, but strategies that promote the health and well‐being of priority populations were needed.
Multifocal nodular facial disease in a 5‐year‐old Whippet cross dog
Authors: Pullens BJ , Remaj B , Hedgespeth BA
Published: December 2024

This case report describes a mycobacterial infection in an adult Whippet cross dog. The dog was diagnosed with Mycolicibacterium sediminis infection, a species of mycobacteria that is yet to be reported as a causative agent of infection in humans or domestic animals. The dog was presented for specialist opinion of a 6‐month history of severe facial lymphadenopathy that was nonresponsive to antibiotic and immunosuppressive therapy. A necrotic lesion developed on her right antebrachium approximately 10–14 days before presentation. The dog was anaesthetised for computed tomography and nodule and skin biopsies including fresh tissue for mycobacterial polymerase chain reaction (PCR). The nodules contained pyogranulomatous inflammation and perivascular necrosis that are typically found in mycobacterial infections. The mycobacterial PCR isolated Mycolicibacterium sediminis. The dog was prescribed triple antibiotic therapy and tapered off corticosteroids, with noticeable improvement within 4 weeks and resolution of granulomas within 3 months of therapy. Presence of chronic dermal pyogranulomatous inflammation should raise suspicions for mycobacterial disease, and fresh tissue should be submitted for PCR to aid in diagnosis.
Comparative morphology of the larval mouthparts among six species of Sphingidae (Insecta: Lepidoptera), with discussions on their diversity
Authors: Yu Tian‐Yu , Cai Wan‐Xin , Jiang Lu
Published: December 2024

Caterpillars have a significant impact on human economy, because their plant‐attacking and silk‐producing habits. The larval mouthparts play a crucial role in feeding and spinning and exhibit an extremely morphological diversity, which is closely related to their taxonomic status, feeding habits, and even the developmental stages. However, the larval mouthparts have not been fully elucidated in the megadiverse Sphingidae. In this study, the larval mouthparts of Ampelophaga rubiginosa Bremer & Grey, 1853, Laothoe amurensis (Staudinger, 1892), Smeritus planus Walker, 1856, Dolbina tancrei Staudinger,1887, Phyllosphingia dissimilis (Bremer, 1861), and Marumba sperchius (Ménétriés, 1857) were morphologically observed and compared using scanning electron microscopy. The mouthparts of six species are morphologically diverse on the labral notches, mandibles, spinneret and labial palps arrangement of the mouthparts. The morphological diversity of larval mouthparts is briefly discussed, considering their taxonomical and functional aspects.
Experiences of imagery in obsessive‐compulsive disorder: An interpretative phenomenological analysis
Authors: Wedge Hannah E. F. , Waddington Louise , Thompson Andrew R.
Published: December 2024

Introduction

Mental imagery is a defining criterion within current OCD diagnoses, and yet little has been written about how this is experienced. This study aimed to investigate how people with a diagnosis of OCD experience imagery, to better understand how this might contribute to the condition.

Methods

This research employed Interpretative Phenomenological Analysis (IPA) and used semi‐structured interviews. An expert‐by‐experience was involved in the study design. Eight adults with an OCD diagnosis were purposively sampled from NHS mental health services and interviewed about their experience of imagery. Interviews were transcribed and analysed in accordance with IPA guidelines. A reflexive log and audit trail were maintained during the research process to enhance quality control and to support the analytical process.

Results

Six superordinate themes were found: Submersion in intense and multifaceted imagery; Overwhelming, uncontrollable imagery; Imagery is explosive and expansive; Imagery involves past memories and future fears; People respond to imagery as if it is real; Therapy shifts imagery.

Conclusions

This study highlights the intensity of OCD‐related imagery experienced by people with OCD and the significance of this imagery in their everyday lives. All participants experienced imagery related to their OCD, demonstrating its importance in the phenomenology of the condition. Images relating to past experiences and images of future fears were identified. Clinicians should routinely seek to include imagery in assessment, formulation, and individual treatment plans for those with OCD.