bluuebunny/crossref_metadata_2025_split huggingface dataset:
C1QA is an invariant biomarker for tissue macrophages
Authors: Horowitz Amir , Yu Haocheng , Pandey Sonalisa , Mishra Bud , Sahoo Debashis 
Published: January 2024

AbstractMacrophages play a pivotal role in immune responses, particularly in the context of combating microbial threats within tissues. The identification of reliable biomarkers associated with macrophage function is essential for understanding their diverse roles in host defense. This study investigates the potential of C1QA as an invariant biomarker for tissue macrophages, focusing on its correlation with the anti-microbial pathway. C1QA, a component of the complement system, has been previously implicated in various immune functions. Our research delves into the specific association of C1QA with tissue-resident macrophages and its implications in the context of anti-microbial responses. Through comprehensive systems biology and Boolean analysis of gene expression, we aim to establish C1QA as a consistent and reliable marker for identifying tissue macrophages. Furthermore, we explore the functional significance of C1QA in the anti-microbial pathway. This research seeks to provide valuable insights into the molecular mechanisms underlying the anti-microbial functions of tissue macrophages, with C1QA emerging as a potential key player in this intricate regulatory network. Understanding the relationship between C1QA, tissue macrophages, and the anti-microbial pathway could pave the way for the development of targeted therapeutic strategies aimed at enhancing the host’s ability to combat infections. Ultimately, our findings contribute to the expanding knowledge of macrophage biology and may have implications for the diagnosis and treatment of infectious diseases.One Sentence SummaryC1QA is a fundamental biomarker of tissue macrophages
Early-stage cancer results in a multiplicative increase in cell-free DNA originating from healthy tissue
Authors: Mamis Konstantinos , Bozic Ivana 
Published: January 2024

AbstractCell-free DNA (cfDNA) is a promising biomarker for cancer detection. However, cfDNA dynamics in the presence of cancer are still poorly understood. Leveraging a rich dataset of cfDNA in healthy individuals and early-stage cancer patients, we find a multiplicative increase in cfDNA concentration in the presence of cancer. This increase is cancer type-specific, ranging from a ∼1.3-fold increase in lung cancer, to a ∼12-fold increase in liver cancer, and does not originate from tumor, but from healthy tissue. Employing an additional dataset reporting the tissue of origin of cfDNA, we observe a significant increase in the correlation between cfDNA originating from leukocytes and from non-leukocyte sources in cancer patients. Introducing a mathematical model for cfDNA dynamics, we find that the observed correlation can be explained by a saturation mechanism in cfDNA clearance. Saturation in clearance implies that smaller increases in cfDNA shedding from healthy tissue due to cancer may lead to the larger observed multiplicative increases in cfDNA levels.
Association of sepsis and delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage
Authors: Centner Franz-Simon , Wenz Holger , Oster Mariella Eliana , Dally Franz-Joseph , Sauter-Servaes Johannes , Pelzer Tanja , Schoettler Jochen Johannes , Hahn Bianka , Abdulazim Amr , Hackenberg Katharina Antonia Margarete , Groden Christoph , Krebs Joerg , Thiel Manfred , Etminan Nima , Maros Máté Elod 
Published: January 2024

AbstractBackgroundAlthough sepsis and delayed cerebral ischemia (DCI) are severe complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) and share pathophysiological features, their interrelation and additive effect on functional outcome is uncertain. We investigated the association of sepsis with DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition.MethodsPatients admitted to our hospital between 11/2014-11/2018 for aSAH were retrospectively analyzed. The main explanatory variable was sepsis, diagnosed using sepsis-3 criteria. Endpoints were DCI and functional outcome at hospital discharge (modified Rankin Scale (mRS) 0-3 vs. 4-6). Propensity score matching (PSM) and multivariable logistic regressions were performed.ResultsOf 238 patients with aSAH, 55 (23%) developed sepsis and 74 (31%) DCI. After PSM, aSAH patients with sepsis displayed significantly worse functional outcome (p<0.01) and longer ICU stay (p=0.046). Sepsis was independently associated with DCI (OR=2.46, 95%CI: 1.28-4.72, p<0.01). However, after exclusion of patients who developed sepsis before (OR=1.59, 95%CI: 0.78-3.24, p=0.21) or after DCI (OR=0.85, 95%CI: 0.37-1.95, p=0.70) this statistical association did not remain. Good functional outcome gradually decreased from 56% (76/135) in patients with neither sepsis nor DCI, to 43% (21/48) in those with no sepsis but DCI, to 34% (10/29) with sepsis but no DCI and to 8% (2/26) in patients with both sepsis and DCI.ConclusionsOur study demonstrates a strong association between sepsis, DCI and functional outcome in patients with aSAH and suggests a complex interplay resulting in a cumulative effect towards poor functional outcome, which warrants further studies.
Increased regional P2X7R uptake detected by [18F]GSK1482160 PET in a tauopathy mouse model
Authors: Kong Yanyan , Cao Lei , Wang Jiao , Zhuang Junyi , Liu Yongshan , Bi Lei , Qiu Yifan , Hou Yuyi , Huang Qi , Xie Fang , Yang Yunhao , Shi Kuangyu , Rominger Axel , Guan Yihui , Jin Hongjun , Ni Ruiqing 
Published: January 2024

AbstractNeuroinflammation plays an important role in Alzheimer’s disease and primary tauopathies. The aim of the current study was to map [18F]GSK1482160 for imaging of purinergic P2X7R in Alzheimer’s disease and primary tauopathy mouse models. MicroPET was performed using [18F]GSK1482160 in widely used mouse models of Alzheimer’s disease (APP/PS1, 5×FAD and 3×Tg), 4-repeat tauopathy (rTg4510) mice and age-matched wild-type mice. Increased uptake of [18F]GSK1482160 was observed in the cortex and basal forebrain of 7-month-old rTg4510 mice compared to age-matched wild-type mice and compared to 3-month-old rTg4510 mice. Nonparametric Spearman’s rank analysis revealed a positive correlation between tau [18F]APN-1607 uptake and [18F]GSK1482160 in the hippocampus of rTg4510 mice. No significant differences in the uptake of [18F]GSK1482160 were observed between wild-type mice and APP/PS1 mice (5, 10 months), 5×FAD mice (3, 7 months) or 3×Tg mice (10 months). Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion compared to wild-type mice. These findings provide in vivo imaging evidence for increased P2X7R in the brains of tauopathy model mice.
Reduced Proactive and Reactive Cognitive Flexibility in Older Adults Underlies Performance Costs During Dual-Task Walking: A Mobile Brain/Body Imaging (MoBI) Study
Authors: Richardson David P. , Foxe John J. , Freedman Edward G. 
Published: January 2024

ABSTRACTAge-related reductions in cognitive flexibility may limit modulation of control processes during systematic increases to cognitive-motor demands, exacerbating dual-task costs. In this study, behavioral and neurophysiologic changes to proactive and reactive control during progressive cognitive-motor demands were compared across older and younger adults to explore the basis for age-differences in cognitive-motor interference (CMI). 19 younger (19 - 29 years old, mean age = 22.84 +/- 2.75 years, 6 male, 13 female) and 18 older (60 - 77 years old, mean age = 67.89 +/- 4.60 years, 9 male, 9 female) healthy adults completed cued task-switching while alternating between sitting and walking on a treadmill. Gait kinematics, task performance measures, and brain activity were recorded using electroencephalography (EEG) based Mobile Brain/Body Imaging (MoBI). Response accuracy on easier trial types improved in younger, but not older adults when they walked while performing the cognitive task. As difficulty increased, walking provoked accuracy costs in older, but not younger adults. Both groups registered faster responses and reduced gait variability during dual-task walking. Older adults exhibited lower amplitude modulations of proactive and reactive neural activity as cognitive-motor demands systematically increased, which may reflect reduced flexibility for progressive preparatory and reactive adjustments over behavioral control.
Efficient enzyme-free isolation of brain-derived extracellular vesicles
Authors: Matamoros-Angles A. , Karadjuzovic E. , Mohammadi B. , Song F. , Brenna S. , Siebels B. , Voß H. , Seuring C. , Ferrer I. , Schlüter H. , Kneussel M. , Altmeppen HC. , Schweizer M. , Puig B. , Shafiq M. , Glatzel M. 
Published: January 2024

AbstractExtracellular vesicles (EVs) have gained significant attention as pathology mediators and potential diagnostic tools for neurodegenerative diseases. However, isolation of brain-derived EVs (BDEVs) from tissue remains challenging, often involving enzymatic digestion steps that may compromise the integrity of EV proteins and overall functionality.Here, we describe that collagenase digestion, commonly used for BDEV isolation, produces undesired protein cleavage of EV-associated proteins in brain tissue homogenates and cell-derived EVs. In order to avoid this effect, we studied the possibility of isolating BDEVs with a reduced amount of collagenase or without any protease. Characterization of the isolated BDEVs revealed their characteristic morphology and size distribution with both approaches. However, we revealed that even minor enzymatic digestion induces ‘artificial’ proteolytic processing in key BDEV markers, such as Flotillin-1, CD81, and the cellular prion protein (PrPC), whereas avoiding enzymatic treatment completely preserves their integrity. We found no differences in mRNA and protein content between non-enzymatically and enzymatically isolated BDEVs, suggesting that we are purifying the same BDEV populations with both approaches. Intriguingly, the lack of Golgi marker GM130 signal, often referred to as contamination contamination-negative marker in EV preparations, seems to result from enzymatic digestion rather than from its actual absence in BDEV samples.Overall, we show that non-enzymatic isolation of EVs from brain tissue is possible and avoids artificial pruning of proteins while achieving a high BDEV yield and purity. This protocol will help to understand the functions of BDEV in a near-physiological setting, thus opening new research approaches.
The deubiquitylating enzyme Fat Facets promotes Fat signalling and restricts tissue growth
Authors: Dawson Lauren E. , Fulford Alexander D. , Sekar Aashika , Ribeiro Paulo S. 
Published: January 2024

AbstractTissue growth is regulated by many signals, including polarity cues. The Hippo signalling pathway restricts tissue growth and receives inputs from the planar cell polarity-controlling Fat signalling pathway. The atypical cadherin Fat restricts growth via several mechanisms that ultimately control the activity of the pro-growth transcriptional co-activator Yorkie. The Fat pathway modulates the activity of the Yorkie inhibitory kinase Warts, as well as the function of the FERM protein Expanded, which promotes Hippo signalling and also directly inhibits Yorkie. Although several Fat pathway activity modulators are known to be involved in ubiquitylation, the role of this post-translational modification in the pathway remains unclear. Moreover, no deubiquitylating enzymes have been described in this pathway. Here, using anin vivoRNAi screening approach, we identify the deubiquitylating enzyme Fat facets as a positive regulator of Fat signalling that is important for tissue growth control. Fat facets interacts genetically and physically with Fat signalling components and regulates transcription of Yorkie target genes. Thus, we uncover a role for reversible ubiquitylation in the control of Fat signalling and, by extension, in the regulation of tissue growth.
Development of the ECLIPSE model of meaningful outcome domains following lower limb amputation and prosthetic rehabilitation, through systematic review and best fit framework synthesis
Authors: Ostler Chantel , Dickinson Alex , Metcalf Cheryl , Donovan-Hall Margaret 
Published: January 2024

AbstractBackgroundLittle is known about which outcome domains characterise meaningful recovery following prosthetic rehabilitation and should be measured. Our previous qualitative work developed a conceptual model of outcome domains which are meaningful to patients. This qualitative synthesis aims to develop that model by exploring views and experiences of recovery captured in the limb loss literature, and use these to produce a second iteration of the model describing outcome domains of importance following prosthetic rehabilitation from the patient’s perspective.MethodsSystematic searches were conducted using CINAHL, Psychinfo and Web of Science from 2011 to early 2023. Studies with a qualitative design focusing on views and experiences of lower limb prosthetic users were eligible for inclusion. Quality was assessed using the CASP tool. ‘Best Fit’ framework synthesis was used to synthesise the evidence and develop the conceptual model.Results40 studies were included, describing the experiences of 539 participants. Data supported the pre-existing conceptual model and led to development of four of the five domains. The newly named ECLIPSE model describes meaningful outcome domains as 1) Being able to participate in important activities and roles, 2) Participating in thewayI want to, 3) My prosthesis works for me, 4) If I am in pain, I can manage it, and 5) I am able to accept my new normal. Studies came from 15 countries showing good coverage of high-income settings. Few participants from low-and-middle-income countries were included, it is unclear if the ECLIPSE model describes outcome domains of importance in these settings.ConclusionsThis synthesis provides a rigorous foundation for understanding outcome domains of importance following lower limb prosthetic rehabilitation from the patient’s perspective. The ECLIPSE model is an accessible representation of recovery which could direct rehabilitation programmes, as well as inform the evaluation of prosthetic care through the selection of outcome measures.
The Two-dose MVA-BN Mpox Vaccine Induces a Nondurable and Low Avidity MPXV-specific Antibody Response
Authors: Oom Aaron L. , Wilson Kesi K. , Yonatan Miilani , Rettig Stephanie , Youn Heekoung Allison , Tuen Michael , Shah Yusra , DuMont Ashley L. , Belli Hayley M. , Zucker Jane R. , Rosen Jennifer B. , Herati Ramin Sedaghat , Samanovic Marie I. , Duerr Ralf , Kottkamp Angelica C. , Mulligan Mark J. ,   the NYC OSMI Study Group
Published: January 2024

AbstractThe 2022 global outbreak of clade IIb mpox was the first major outbreak of mpox outside of African nations. To control the outbreak, public health officials began vaccination campaigns using the third-generation orthopoxvirus vaccine MVA-BN. Prior to this outbreak, the durability of MPXV-specific immunity induced by MVA-BN was poorly understood. In 2022, we launched the New York City Observational Study of Mpox Immunity (NYC OSMI,NCT05654883), a longitudinal study of 171 participants comprising MVA-BN vaccinees and mpox convalescent individuals. Peripheral blood sampling was performed at intervals including prior to vaccination, after one dose, and after the second dose. MVA-BN vaccinees with and without a history of smallpox vaccination demonstrated detectable mpox virus (MPXV)-specific memory B cells at one-year post-vaccination. Additionally, MVA-BN increased MPXV neutralizing titers in smallpox vaccine-naïve vaccinees, with a comparable peak titer reached in naïve and smallpox vaccine-experienced vaccinees. However, neutralizing titers returned to baseline within 5-7 months for naïve individuals, while remaining elevated in those with prior smallpox vaccination. Both naïve and experienced individuals generated robust, immunodominant IgG responses against MPXV H3 and A35, but naïve vaccinees’ IgG responses showed lower avidity than experienced vaccinees. These data highlight a low avidity antibody response elicited by MVA-BN that is short-lived in naïve vaccinees. This work supports the need for long-term studies on protection induced by MVA-BN including the potential need for booster doses as well as the development of next-generation orthopoxvirus vaccines.
Self-organizing glycolytic waves fuel cell migration and cancer progression
Authors: Zhan Huiwang , Pal Dhiman Sankar , Borleis Jane , Janetopoulos Chris , Huang Chuan-Hsiang , Devreotes Peter N. 
Published: January 2024

SummaryGlycolysis has traditionally been thought to take place in the cytosol but we observed the enrichment of glycolytic enzymes in propagating waves of the cell cortex in human epithelial cells. These waves reflect excitable Ras/PI3K signal transduction and F-actin/actomyosin networks that drive cellular protrusions, suggesting that localized glycolysis at the cortex provides ATP for cell morphological events such as migration, phagocytosis, and cytokinesis. Perturbations that altered cortical waves caused corresponding changes in enzyme localization and ATP production whereas synthetic recruitment of glycolytic enzymes to the cell cortex enhanced cell spreading and motility. Interestingly, the cortical waves and ATP levels were positively correlated with the metastatic potential of cancer cells. The coordinated signal transduction, cytoskeletal, and glycolytic waves in cancer cells may explain their increased motility and their greater reliance on glycolysis, often referred to as the Warburg effect.
Opposing Sequential Biases in Direction and Time Reproduction: Influences of Task Relevance and Working Memory
Authors: Cheng Si , Chen Siyi , Shi Zhuanghua 
Published: January 2024

AbstractOur current perception and decision-making are shaped by recent experiences, a phenomenon known as serial dependence. While serial dependence is well-documented in visual perception and has been recently explored in time perception, their functional similarities across non-temporal and temporal domains remain elusive, particularly in relation to task relevance and working memory load. To address this, we designed a unified experimental paradigm using coherent motion stimuli to test both direction and time reproduction. The direction and time tasks were randomly mixed across trials. Additionally, we introduced pre-cue versus post-cue settings in separate experiments to manipulate working memory load during the encoding phase. We found attractive biases in time reproduction but repulsive biases in direction estimation. Notably, the temporal attraction was more pronounced when the preceding task was also time-related. In contrast, the direction repulsion remained unaffected by the nature of the preceding task. Additionally, both attractive and repulsive biases were enhanced by the post-cue compared to the pre-cue. Our findings suggest that opposing sequential effects in non-temporal and temporal domains may originate from different processing stages linked to sensory adaptation and post-perceptual processes involving working memory.
Physical Activity, Sedentary Behavior and Microbiome: A Systematic Review and Meta-analysis
Authors: Pérez-Prieto Inmaculada , Plaza-Florido Abel , Ubago-Guisado Esther , Ortega Francisco B. , Altmäe Signe 
Published: January 2024

ABSTRACTBackgroundThe effects of physical activity and sedentary behavior on human health are well known, however, the molecular mechanisms are poorly understood. Growing evidence points to physical activity as an important modulator of the microbial composition, while evidence of sedentary behavior is scarce. We aimed to synthesize and meta-analyze the current evidence about the effects of physical activity and sedentary behavior on microbiome across different body sites and in different populations.MethodsA systematic search in PubMed, Web of Science, Scopus and Cochrane databases was conducted until September 2022. Random-effects meta-analyses including cross-sectional studies (activevs. inactive / athletesvs. non-athletes) or trials reporting the chronic effect of physical activity interventions on gut microbiome alpha-diversity in healthy individuals were performed.ResultsNinety-one studies were included in this systematic review. Our meta-analyses of 2632 participants indicated no consistent effect of physical activity on microbial alpha-diversity, although there seems to be a trend toward a higher microbial richness in athletes compared to non-athletes. We observed an increase in short-chain fatty acids-producing bacteria such asAkkermansia,Faecalibacterium,VeillonellaorRoseburiain active individuals and after physical activity interventions.ConclusionsPhysical activity levels were positively associated with the relative abundance of short-chain fatty acids-producing bacteria. Athletes seem to have a richer microbiome compared to non-athletes. However, high heterogeneity between studies avoids to obtain conclusive information on the role of physical activity in microbial composition. Future multi-omics studies would enhance our understanding of the molecular effects of physical activity and sedentary behavior on the microbiome.
Polycomb Repressive Complex 1.1 Component, BCOR, Promotes Syncytiotrophoblast Differentiation in Mice and Humans
Authors: Sadowski Danielle , Corcoran Connie M. , Abdi Riyan , Zheng Teng , Okae Hiroaki , Arima Takahiro , Bardwell Vivian J. , Gearhart Micah D. 
Published: January 2024

AbstractEarly defects in placenta development are thought to underlie a range of adverse pregnancy conditions including miscarriage, fetal growth abnormalities, preeclampsia, and stillbirth. Differentiating trophoblast stem cells undergo a choreographed allocation of syncytiotrophoblast and extravillous trophoblast cells in response to signaling cues from the developing fetus and the uterine environment. The expression and activity of transcription factors and chromatin modifying enzymes change during differentiation to appropriately reshape the chromatin landscape in each cell type. We have previously found in mice that extraembryonic loss of BCOR, a conserved component of the epigenetic silencing complex Polycomb Repressive Complex 1.1 (PRC1.1), leads to a reduced labyrinth and expanded trophoblast giant cell population in the placenta. Molecular analysis of wild-type and BCOR loss-of-function male and female placentas by RNA-seq identified gene expression changes as early as E6.5. We found that BCOR is required to down regulate stem cell genes and repress factors that promote alternate lineages which leads to reduced levels of syncytiotrophoblasts. ChIP-seq experiments identified a number of directly bound functional targets includingPdgfaandWnt7b. In humans,BCORis mutated in X-linked syndromes involving fetal growth restriction and females with a heterozygous null mutation inBCORcan experience recurrent miscarriages. To establish a direct role forBCORin human placental development, we used CRISPR/Cas9 to knockoutBCORin male (CT29) and female (CT30) human trophoblast stem cells. Mutant cell lines retained capacity for induced differentiation into syncytiotrophoblast and extravillous trophoblasts and exhibited minimal changes in gene expression. However, in 3D cell culture using trophoblast organoid media,BCORknockout lines had significantly altered gene expression including homologs of stem cell genes upregulated inBcorknockout mice. CUT&RUN experiments in self-renewing and 3D cell culture identified genes directly bound by BCOR. Single cell profiling of wild type, knockout, and a P85L pathogenic knock-inBCORmutation showed a reduced capacity to differentiate into syncytiotrophoblasts after four days of differentiation. Together, these results suggest that BCOR is a conserved regulator of trophoblast development that represses stem cell genes during differentiation and maintains lineage fidelity by repressing genes that promote alternate cell fates.