bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular matrix dependent regulation of Septin 7 in focal adhesions promotes mechanosensing and response in fibroblasts
Authors: Sturgess Wesley , Packirisamy Swathi , Geneidy Rodina , Swaminathan Vinay 
Published: February 2024

AbstractFibroblasts are contractile adherent cells that maintain tissue homeostasis by sensing a wide array of changes in the extracellular matrix (ECM) and in response, regulate the physical and compositional properties of the ECM. These diverse cues are sensed by focal adhesions (FAs) that differentially couple changes in the ECM to the actomyosin machinery via modulation of integrin activation and the resultant recruitment of several proteins. One such protein is Septin-7 (Sept-7) that belongs to the septin family and has been found in FA proteomics and interactome studies. Sept-7 however, is not considered an FA protein and is thought to regulate and be regulated by actin outside of FAs. To reconcile these differences, here we used total internal reflection microscopy to image Sept-7 localization and dynamics at the cell-ECM interface and found that that ECM-mediated integrin activation in fibroblasts regulates the formation of spatially distinct higher order Sept-7 structures at FA subpopulations. In and around FAs located in the perinuclear regions of the cell, ECM binding resulted in the formation and stabilization of Sept-7 bundles while ECM binding and complete integrin activation promoted the growth of FA-like elongated Sept-7 structures that dynamically associated with the core of peripheral FAs. Functionally, peripheral Sept-7 structures promoted the elongation of peripheral FAs while perinuclear Sept-7 bundles were critical in regulating the maturation and stabilization of perinuclear FAs. Due to this coupling between the ECM, integrin activation and regulation of Sept-7 structures, we found that Sept-7 is required for a wide range of ECM sensing functions in fibroblasts including modulating sensitivity to changes in ECM stiffness and density and in contributing to the cells ability to remodel the ECM. Collectively, our results show that Sept-7 is an FA protein that gets recruited and assembled in diverse higher order structures in an ECM dependent manner to differentially regulate FA subpopulations and promote mechanosensing and ECM remodelling functions in fibroblasts.
Chemically induced senescence prompts functional changes in human microglia-like cells
Authors: Armanville S. , Tocco C. , Haj Mohamad Z. , Clarke D. , Robitaille R. , Drouin-Ouellet J. 
Published: February 2024

AbstractIn response to various stressors, cells can enter a state called cellular senescence which is characterized by irreversible cell cycle arrest and a senescence-associated secretory phenotype (SASP). The progressive accumulation of senescent glial cells in the central nervous system (CNS) with aging suggests a potential role for senescence as driver of aging and inflammation in the brain. As the main immune cell population residing in the CNS, microglia are thought to play a pivotal role in the progression of age-associated neuroinflammation. Furthermore, due to their slow turnover, microglia are highly susceptible to undergoing cellular senescence. However, current understanding of age-related changes in microglia and their impact on brain aging is limited. Due to the challenge in accessing human primary microglia and the lack of models to adequately recapitulate aging, this knowledge is predominantly limited to rodent studies. Here, we chemically induced senescence in a human immortalized microglia cell line with a cocktail of senescence-inducing molecules. We demonstrate that chemically induced senescent microglia adopt a pro-inflammatory phenotype, have reduced phagocytic activity and impaired calcium activity. Our results show that chemically induced senescence can mimic features of cellular aging and can provide insight on the impact of aging and cellular senescence on human microglia.
Single-cell approach dissectingagrquorum sensing dynamics inStaphylococcus aureus
Authors: Bär Julian , Charlton Samuel G. V. , Tarnutzer Andrea , Ugolini Giovanni Stefano , Secchi Eleonora , Zinkernagel Annelies S. 
Published: February 2024

AbstractStaphylococcus aureusboth colonizes humans and causes severe virulent infections. Virulence is regulated by theagrquorum sensing system and its autoinducing peptide (AIP), with dynamics at the single-cell level across fouragr-types – each defined by distinct AIP sequences and capable of cross-inhibition – remaining elusive. Employing microfluidics, time-lapse microscopy, and deep-learning image analysis, we uncovered significant differences in AIP sensitivity amongagr-types. We observed bimodalagractivation, attributed to intergenerational phenotypic stability and influenced by AIP concentration. Upon AIP stimulation,agr-IIIshowed AIP insensitivity, whileagr-IIexhibited increased sensitivity and prolonged generation time. Beyond expected cross-inhibition ofagr-Iby heterologous AIP-II and -III, the presumably cross-activating AIP-IV also inhibitedagr-I. Community interactions across differentagr-type pairings revealed four main patterns: stable or switched dominance, and delayed or stable dual activation, influenced by community characteristics. These insights underscore the potential of personalized treatment strategies considering virulence and genetic diversity.
Cross-species alignment along the chronological axis reveals evolutionary effect on structural development of human brain
Authors: Li Yue , Sun Qinyao , Zhu Shunli , Chu Congying , Wang Jiaojian 
Published: February 2024

AbstractDisentangling evolution mysteries of human brain has always been an imperative endeavor in neuroscience. On the one hand, by spatially aligning the brains between human and nonhuman primates (NHPs), previous efforts in comparative studies revealed both correspondence and difference in brain anatomy, e.g., the morphological and the connectomic patterns. On the other hand, brain anatomical development along the temporal axis is evident for both human and NHPs in early life. However, it remains largely unknown whether we can conjugate the brain development phases between human and NHPs, and, especially, what the role played by the brain anatomy in the conjugation will be. Here, we proposed to embed the brain anatomy of human and macaque in the chronological axis for enabling the cross-species comparison on brain development. Specifically, we separately established the prediction models by using the brain anatomical features in gray matter and white matter tracts to predict the chronological age in the human and macaque samples with brain development. We observed that applying the trained models within-species could well predict the chronological age. Interestingly, by conducting the cross-species application of the trained models, e.g., applying the model trained in humans to the data of macaques, we found a significant cross-species imbalance regarding to the model performance, in which the model trained in macaque showed a higher accuracy in predicting the chronological age of human than the model trained in human in predicting the chronological age of macaque. The cross application of the trained model introduced the brain cross-species age gap (BCAP) as an individual index to quantify the cross-species discrepancy along the temporal axis of brain development for each participant. We further showed that BCAP was associated with the behavioral performance in both visual sensitivity test and picture vocabulary test in the human samples. Taken together, our study situated the cross-species brain development along the chronological axis, which highlighted the disproportionately anatomical development in the human brain to extend our understanding of the potential evolutionary effects.
SUMO-mediated regulation of a H3K4me3 reader controls germline development inC. elegans
Authors: Carvalho Cátia A. , Abu-Shach Ulrike Bening , Raju Asha , Vershinin Zlata , Levy Dan , Boxem Mike , Broday Limor 
Published: February 2024

AbstractULP-2 is a conserved SUMO protease required for embryonic development inC. elegans. Here we revealed that ULP-2 controls germline development by regulating the PHD-SET domain protein, SET-26. Specifically, theulp-2mutant hermaphrodites exhibit increased sterility and progressive elevation in global protein sumoylation. In the progeny of homozygous animals, meiosis is arrested at the diplotene stage and the cells in the proximal germline acquire a somatic fate. Germline RNAseq analysis revealed the downregulation of numerous germline genes, whereas somatic gene expression is upregulated inulp-2mutant gonads. To determine the key factors that are regulated by ULP-2, we performed a yeast two-hybrid screen and identified the H3K4me3 reader, SET-26. Genetic interaction was observed in double mutantulp-2;set-26resulting in enhanced sterility phenotype to complete sterility in the first generation of homozygous offspring. Consistently, SET-26 is sumoylated and its sumoylation levels are regulated by ULP-2. Moreover, we detected reduction in H3K4me3 levels bound to SET-26 in theulp-2mutant background. A comparative proteomics screen between WT andulp-2loss of activity identified the predicted methyltransferase SET-27 as a ULP-2-dependent SET-26-associated protein. SET-27 knockout genetically interacts with ULP-2 in the germline, but not with SET-26. Taken together, we revealed a ULP-2/SET-26 axis which is required for the maintenance and regulation of germline development.
Stable flies are bonafide reservoirs of mastitis-associated bacteria
Authors: Sommer Andrew J. , Kettner Julia E. , Coon Kerri L. 
Published: February 2024

ABSTRACTHematophagousStomoxys(stable) fly populations in dairy barns are sustained by a constant availability of cattle hosts and manure, which serve as major reservoirs of both zoonotic and opportunistic bacterial pathogens. However, the overall composition and diversity of bacterial communities associated withStomoxysflies and the ability of biting flies to acquire and transmit potentially pathogenic bacteria present in their surrounding environment remain to be investigated. Here, we present the first culture-independent examination ofStomoxys-associated bacterial communities through longitudinal sampling of fly and manure samples collected from two connected dairy facilities in South Central Wisconsin. High throughput 16S rRNA gene amplicon sequencing was used to characterize and compare bacterial communities present on or within flies and in manure collected from the same facility. Bacterial alpha diversity was overall higher in manure samples as compared to fly samples, with manure-associated bacterial communities being dominated by members of the Bacteroidales, Eubacteriales, and Oscillospirales. In contrast, flies harbored relatively low-complexity communities dominated by members of the Enterobacterales, Staphylococcales, and Lactobacillales. Clinically relevant bacterial strains, includingEscherichiaspp. and other taxa associated with mastitic cows housed in the same facilities, were detected in paired fly and manure samples but exhibited dramatically elevated abundances in fly samples as compared to manure samples. Viable colonies ofEscherichia,Klebsiella, andStaphylococcusspp. were also readily isolated from fly samples, confirming that flies harbor culturable mastitis associated bacteria. This study provides definitive support for a potential role for biting flies in mediating bacterial pathogen transmission in dairy barns and other agricultural settings.IMPORTANCEDisease prevention on dairy farms has significant implications for cattle health, food security, and zoonosis. Of particular importance is the control of bovine mastitis, which can be caused by a diverse array of environmental bacterial pathogens, includingKlebsiella,E. coli,Streptococcus, andStaphylococcusspp. Despite being one of the most significant and costly cattle diseases worldwide, the epidemiology of bovine mastitis is not well understood. This study provides the first culture-dependent and culture-independent evidence to support the potential for biting flies to transmit opportunistic bovine and human pathogens in agricultural settings. It also links carriage of specific bacterial taxa in flies to clinical mastitis cases in cows housed in the same facility at the time of sampling. Altogether, these results indicate that biting flies represent an important, yet understudied biosecurity threat to animal husbandry facilities.
Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity
Authors: Otero Claire E. , Petkova Sophia , Ebermann Martin , Taher Husam , John Nessy , Hoffmann Katja , Davalos Angel , Moström Matilda J. , Gilbride Roxanne M , Papen Courtney R. , Barber-Axthelm Aaron , Scheef Elizabeth A. , Barfield Richard , Sprehe Lesli M. , Kendall Savannah , Manuel Tabitha D. , Vande Burgt Nathan H. , Chan Cliburn , Denton Michael , Streblow Zachary J. , Streblow Daniel N. , Hansen Scott G , Kaur Amitinder , Permar Sallie , Früh Klaus , Hengel Hartmut , Malouli Daniel , Kolb Philipp 
Published: February 2024

AbstractHuman cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activationin vitro, but their role in infection and pathogenesis is unknown. To examine thein vivofunction of vFcγRs in animal hosts closely related to humans, we identified and characterized vFcγRs encoded by rhesus CMV (RhCMV). We demonstrate that Rh05, Rh152/151 and Rh173 represent the complete set of RhCMV vFcγRs, each displaying functional similarities to their respective HCMV orthologs with respect to antagonizing host FcγR activationin vitro. When RhCMV-naïve rhesus macaques were infected with vFcγR-deleted RhCMV, peak plasma viremia levels and anti-RhCMV antibody responses were comparable to wildtype infections. However, the duration of plasma viremia was significantly shortened in immunocompetent, but not in CD4+ T cell-depleted animals. Since vFcγRs were not required for superinfection, we conclude that vFcγRs delay control by virus-specific adaptive immune responses, particularly antibodies, during primary infection.
Engineering an Escherichia coli strain for production of long single-stranded DNA
Authors: Shen Konlin , Flood Jake J. , Zhang Zhihuizi , Ha Alvin , Shy Brian R. , Dueber John E. , Douglas Shawn M. 
Published: February 2024

AbstractLong single-stranded DNA (ssDNA) is a versatile molecular reagent with applications including RNA- guided genome engineering and DNA nanotechnology, yet its production is typically resource-intensive. We introduce a novel method utilizing an engineeredE. coli “helper”strain and phagemid system that simplifies long ssDNA generation to a straightforward transformation and purification procedure. Our method obviates the need for helper plasmids and their associated contamination by integrating M13mp18 genes directly into theE. colichromosome. We achieved ssDNA lengths ranging from 504 to 20,724 nucleotides with titers up to 250 μg/L following alkaline-lysis purification. The efficacy of our system was confirmed through its application in primary T cell genome modifications and DNA origami folding. The reliability, scalability, and ease of our approach promises to unlock new experimental applications requiring large quantities of long ssDNA.
A multi-looping chromatin signature predicts dysregulated gene expression in neurons with familial Alzheimer’s disease mutations
Authors: Chandrashekar Harshini , Simandi Zoltan , Choi Heesun , Ryu Han-Seul , Waldman Abraham J. , Nikish Alexandria , Muppidi Srikar S. , Gong Wanfeng , Paquet Dominik , Phillips-Cremins Jennifer E. 
Published: February 2024

AbstractMammalian genomes fold into tens of thousands of long-range loops, but their functional role and physiologic relevance remain poorly understood. Here, using human post-mitotic neurons with rare familial Alzheimer’s disease (FAD) mutations, we identify hundreds of reproducibly dysregulated genes and thousands of miswired loops prior to amyloid accumulation and tau phosphorylation. Single loops do not predict expression changes; however, the severity and direction of change in mRNA levels and single-cell burst frequency strongly correlate with the number of FAD-gained or -lost promoter-enhancer loops. Classic architectural proteins CTCF and cohesin do not change occupancy in FAD-mutant neurons. Instead, we unexpectedly find TAATTA motifs amenable to binding by DLX homeodomain transcription factors and changing noncoding RNAPolII signal at FAD-dynamic promoter-enhancer loops.DLX1/5/6mRNA levels are strongly upregulated in FAD-mutant neurons coincident with a shift in excitatory-to-inhibitory gene expression and miswiring of multi-loops connecting enhancers to neural subtype genes.DLX1overexpression is sufficient for loop miswiring in wildtype neurons, including lost and gained loops at enhancers with tandem TAATTA arrays and singular TAATTA motifs, respectively. Our data uncover a genome structure-function relationship between multi-loop miswiring and dysregulated excitatory and inhibitory transcriptional programs during lineage commitment of human neurons homozygously-engineered with rare FAD mutations.
O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle control
Authors: Mitchell Conor W. , Yuan Huijie , Sønderstrup-Jensen Marie , Authier Florence , D’Alessio Alfonso Manuel , Ferenbach Andrew T. , van Aalten Daan M.F. 
Published: February 2024

AbstractO-GlcNAcylation is an evolutionary conserved post-translational modification implicated in neurodevelopment. Missense variants of O-GlcNAc transferase (OGT) are causal for the intellectual disability syndrome OGT Congenital Disorder of Glycosylation (OGT-CDG). The observation of microcephaly in OGT-CDG patients suggests that dysregulation of the cell cycle and aberrant neurogenesis may contribute to disease aetiology. Here, we identify Ser584 O-GlcNAcylation of DDX3X, a known intellectual disability and microcephaly associated protein, as a key regulator of G1/S-phase transition, inhibiting proteasome-dependent degradation of DDX3X. DDX3X levels are reduced in a mouse model of OGT-CDG, alongside the DDX3X-target gene and synaptogenic regulator cyclin E1. These data reveal how a single DDX3X O-GlcNAc site exerts control of the cell cycle and highlights dysregulation of DDX3X-dependent translation, and concomitant impairments in cortical neurogenesis, as a possible pathway disrupted in OGT-CDG.
Phase-controlled heat modulation with Aharonov-Bohm interferometers
Authors: Hwang Sun-Yong , Sothmann Björn , López Rosa 
Published: February 2024

A heat modulator is proposed based on a voltage-biased Aharonov-Bohm interferometer. Once an electrical bias is applied, Peltier effects give rise to a flow of heat that can be modulated by a magnetic flux. We determine the corresponding temperature changes using a simple thermal model. Our calculations demonstrate that the modulated temperature difference can be as large as 80 mK at base temperature about 600 mK with relative temperature variations reaching 10%. Our model also predicts, quite generally, the emergence of spin-polarized heat flows without any ferromagnetic contacts, if Rashba spin-orbit interaction is combined with the applied magnetic flux, which potentially paves the way towards caloritronic information processing.

Published by the American Physical Society
2024
Observation of weak localization in dual-gated bilayer
MoS2
Authors: Qu Tingyu , Masseroni Michele , Taniguchi Takashi , Watanabe Kenji , Özyilmaz Barbaros , Ihn Thomas , Ensslin Klaus 
Published: February 2024

We investigate the magnetoresistance of a dual-gated bilayer MoS2 encapsulated by hexagonal boron nitride. At low magnetic fields (|B|<0.5T), we observe a negative magnetoresistance, which we identify as the weak localization effect. We determine both the phase coherence length and mean free path as a function of electron density and displacement field. Both characteristic lengths show a similar monotonic increase with electron density, while they are not affected by the displacement field. We further investigate the dephasing mechanism by measuring the temperature dependence of the phase coherence length. Our results suggest that when only the lower spin-orbit split bands (K↑, K′↓) contribute to transport is Coulomb scattering the dominant source of decoherence, while intervalley scattering seems not to play a relevant role in this regime. This observation is consistent with the picture of spin-polarized valleys (spin-valley locking), where the intrinsic spin-orbit coupling protects the spin states, rather than introducing an additional dephasing mechanism as in other materials.

Published by the American Physical Society
2024
Spatiotemporal Torquing of Light
Authors: Hancock S. W. , Zahedpour S. , Goffin A. , Milchberg H. M. 
Published: February 2024

We demonstrate the controlled spatiotemporal transfer of transverse orbital angular momentum (OAM) to electromagnetic waves: the spatiotemporal torquing of light. This is a radically different situation from OAM transfer to longitudinal, spatially defined OAM light by stationary or slowly varying refractive-index structures such as phase plates or air turbulence. We show that net transverse OAM per photon can be spatiotemporally imparted to a light pulse only if (1) a transient phase perturbation is well overlapped with the pulse in spacetime, or (2) the pulse initially has nonzero transverse OAM density, and the perturbation removes energy from it. Physical insight is provided by the mechanical analogy of torquing a wheel or removing mass as it spins. Our OAM theory for spatiotemporal optical vortex (STOV) pulses [S. W. Hancock ,] correctly quantifies the light-matter interaction of our experiments and provides a spatiotemporal-torque-based explanation for the first measurement of STOVs [N. Jhajj , ].

Published by the American Physical Society
2024
Accessing the effect of smartphone agricultural applications on land transfer: evidence from Sichuan province in China
Authors: Yu Xi , Abdulai Awudu , Li Dongmei 
Published: February 2024

PurposeThis study aims to examine farmers' decision to use smartphone agricultural applications (SAAs) and how SAAs adoption impact their land transfer behaviors in terms of the current land transfer-in area (LTA) and the future willingness to renew land transfer-in after it expires (WTR).Design/methodology/approachThis study provides empirical evidence on the relationship between farmers' use of SAAs and land transfer choice, using a field survey data of 752 rural farm households in 2020 from Sichuan province of China. The endogenous switching models are employed to address potential self-selection bias associated with voluntary SAAs use and to quantitatively examine the impacts of SAAs use on land transfer choice.FindingsThe empirical results reveal that SAAs significantly improves the probability of transfer-in of more land by 39.10%. We find SAAs use has heterogeneous impacts on land transfer-in choice in the groups of agricultural technology, extension service, marketing and credit. Besides, we also find that SAAs use exerts highly positive and significant impact on farmers with less land area transfer-in. Moreover, SAAs can increase the probability of farmers' willingness to renew the land transfer-in by 30%.Originality/valueTo the best of our knowledge, this study is the first to explore the quantitative relationship between the use of SAAs and farm households' land transfer choice. The findings of this work can provide policy-related insights to help government promote the development of digital applications in the agricultural sector.