bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling molecular dynamics in living cells: Fluorescent protein biosensors for cell biology
Authors: Sanchez Colline , Ramirez Andrea , Hodgson Louis 
Published: February 2024

AbstractGenetically encoded, fluorescent protein (FP)‐based Förster resonance energy transfer (FRET) biosensors are microscopy imaging tools tailored for the precise monitoring and detection of molecular dynamics within subcellular microenvironments. They are characterised by their ability to provide an outstanding combination of spatial and temporal resolutions in live‐cell microscopy. In this review, we begin by tracing back on the historical development of genetically encoded FP labelling for detection in live cells, which lead us to the development of early biosensors and finally to the engineering of single‐chain FRET‐based biosensors that have become the state‐of‐the‐art today. Ultimately, this review delves into the fundamental principles of FRET and the design strategies underpinning FRET‐based biosensors, discusses their diverse applications and addresses the distinct challenges associated with their implementation. We place particular emphasis on single‐chain FRET biosensors for the Rho family of guanosine triphosphate hydrolases (GTPases), pointing to their historical role in driving our understanding of the molecular dynamics of this important class of signalling proteins and revealing the intricate relationships and regulatory mechanisms that comprise Rho GTPase biology in living cells.
Differences in prevalence of self‐reported oral hypofunction between older adult patients with rheumatoid arthritis and the general older population: A cross‐sectional study using propensity score matching
Authors: Kudo Yoko , Takeuchi Kenji , Kusama Taro , Kojima Toshihisa , Waguri‐Nagaya Yuko , Nagayoshi Mako , Kondo Katsunori , Mizuta Kentaro , Osaka Ken , Kojima Masayo 
Published: February 2024

AbstractObjectiveTo examine the association between rheumatoid arthritis (RA) and oral hypofunction (OHF) using propensity score matching (PSM) to adjust for differences between older adults with RA and the general older adult population.MethodsWe conducted a cross‐sectional survey among 189 older adults with RA in 2019 (mean age, 71.9 ± 3.6) and 47 178 independent older adult residents in 2016 (mean age, 71.6 ± 4.0), respectively. The questionnaire covered information on socio‐demographic characteristics and OHF for both groups. Age, sex, educational level and smoking history were used to determine PSM. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of self‐reported OHF (fewer remaining teeth, decreased masticatory function, deterioration of swallowing function and oral dryness) were estimated using Poisson regressions.ResultOHF was observed in 44.4% of patients with RA and 27.5% of residents. Before PSM, the prevalence of OHF among patients with RA was higher than that of residents (PR, 1.75; 95% CI, 1.50–2.05). After PSM, there were 189 patients with RA and residents, and the prevalence of OHF among patients with RA was still higher (PR, 1.61; 95% CI, 1.22–2.13). Poisson regression showed that the prevalence of 19 or fewer teeth (PR, 1.06; 95% CI, 0.82–1.36), difficulties eating tough foods (PR, 1.18; 95% CI, 0.90–1.55), difficulties swallowing tea or soup (PR, 1.77; 95% CI, 1.19–2.63), and dry mouth (PR, 2.79; 95% CI, 1.90–4.07) was higher among patients with RA than residents.ConclusionCompared with the general older adult population, patients with RA have a higher prevalence of self‐reported OHF.
Performance Analysis of a Gripper for Microsatellite Berthing
Authors: Titov Alexander , Russo Matteo , Ceccarelli Marco 
Published: February 2024

Abstract
In this paper, the grasping operation of CubeSat microsatellites is analyzed with a topological study of grasping strategies as functions of CubeSat geometry. Grasping conditions and limitations are introduced for the square-profiled bodies of CubeSats of 1U and 12U sizes. A topology search defines fingertip forms and configurations to fulfill requirements, and operational limitations are presented in terms of geometry and dynamic parameters. The grasping performance is then analyzed in the side grasp and corner grasp cases and validated with a numerical case study.
Genome streamlining to improve performance of a fast-growing cyanobacterium
Synechococcus elongatus
UTEX 2973
Authors: Sengupta Annesha , Bandyopadhyay Anindita , Sarkar Debolina , Hendry John I. , Schubert Max G. , Liu Deng , Church George M. , Maranas Costas D. , Pakrasi Himadri B. 
Published: February 2024

ABSTRACT

Cyanobacteria are photosynthetic organisms that have garnered significant recognition as potential hosts for sustainable bioproduction. However, their complex regulatory networks pose significant challenges to major metabolic engineering efforts, thereby limiting their feasibility as production hosts. Genome streamlining has been demonstrated to be a successful approach for improving productivity and fitness in heterotrophs but is yet to be explored to its full potential in phototrophs. Here, we present the systematic reduction of the genome of the cyanobacterium exhibiting the fastest exponential growth,
Synechococcus elongatus
UTEX 2973. This work, the first of its kind in a photoautotroph, involved an iterative process using state-of-the-art genome-editing technology guided by experimental analysis and computational tools. CRISPR-Cas3 enabled large, progressive deletions of predicted dispensable regions and aided in the identification of essential genes. The large deletions were combined to obtain a strain with 55-kb genome reduction. The strains with streamlined genome showed improvement in growth (up to 23%) and productivity (by 22.7%) as compared to the wild type (WT). This streamlining strategy not only has the potential to develop cyanobacterial strains with improved growth and productivity traits but can also facilitate a better understanding of their genome-to-phenome relationships.

IMPORTANCE
Genome streamlining is an evolutionary strategy used by natural living systems to dispense unnecessary genes from their genome as a mechanism to adapt and evolve. While this strategy has been successfully borrowed to develop synthetic heterotrophic microbial systems with desired phenotype, it has not been extensively explored in photoautotrophs. Genome streamlining strategy incorporates both computational predictions to identify the dispensable regions and experimental validation using genome-editing tool, and in this study, we have employed a modified strategy with the goal to minimize the genome size to an extent that allows optimal cellular fitness under specified conditions. Our strategy has explored a novel genome-editing tool in photoautotrophs, which, unlike other existing tools, enables large, spontaneous optimal deletions from the genome. Our findings demonstrate the effectiveness of this modified strategy in obtaining strains with streamlined genome, exhibiting improved fitness and productivity.
Long-term safety and effectiveness of canakinumab in patients with monogenic autoinflammatory diseases: results from the interim analysis of the RELIANCE registry
Authors: Kuemmerle-Deschner Jasmin B , Kallinich Tilmann , Henes Joerg , Kortus-Götze Birgit , Oommen Prasad T , Rech Juergen , Krickau Tobias , Weller-Heinemann Frank , Horneff Gerd , Janda Aleš , Foeldvari Ivan , Schuetz Catharina , Dressler Frank , Borte Michael , Hufnagel Markus , Meier Florian , Fiene Michael , Andreica Ioana , Weber-Arden Julia , Blank Norbert 
Published: February 2024

ObjectiveInterim analysis of the RELIANCE registry, an on-going, non-interventional, open-label, multicentre, prospective study evaluating the long-term safety, dosing regimens and effectiveness of canakinumab in patients with cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), tumour-necrosis factor receptor-associated periodic syndrome (TRAPS) or mevalonate-kinase deficiency (MKD)/hyperimmunoglobulin-D syndrome (HIDS).MethodsFrom September 2017 for patients with CAPS, and June 2018 for patients with FMF, TRAPS or MKD/HIDS, the registry enrolled paediatric (aged ≥2 years) and adult patients (aged ≥18 years) receiving canakinumab as part of their routine medical care. Safety, canakinumab dose, disease activity and quality of life outcome measures were evaluated at baseline and every 6 months until end of study visit.ResultsAt the analysis cut-off date (December 2020), 168 patients (91 CAPS, 54 FMF, 16 TRAPS and 7 MKD/HIDS) were enrolled. 85 (50.9%) patients were female and 72 (43.1%) were children (<18 years). The median patient age was 20.0 years (range 2.0–79.0 years). In the CAPS cohort, serious infections and serious adverse drug-reactions were more common in patients receiving higher than the recommended starting dose (SD) of canakinumab. A trend to receive >SD of canakinumab was observed in the pooled population. The majority of patients were reported as having either absent or mild/moderate disease activity (physician’s global assessment) from baseline to Month 30, with a stable proportion of patients (~70%) in remission under canakinumab treatment. Patient-reported disease activity (Visual Analogue Scale (VAS), Autoinflammatory Disease Activity Index), fatigue (VAS); markers of inflammation (C-reactive protein, serum amyloid A and erythrocyte sedimentation rate) remained well-controlled throughout.ConclusionData from this analysis confirm the long-term safety and effectiveness of canakinumab for the treatment of CAPS, FMF, TRAPS and MKD/HIDS.
Evaluating the design of the first marine protected area network in Pacific Canada under a changing climate
Authors: Rubidge Emily M. , Robb Carrie K. , Thompson Patrick L. , McDougall Chris , Bodtker Karin M. , Gale Katie S.P. , Ban Stephen , Tayler Brown Kil Hltaanuwaay , Sahanatien Vicki , Ouchi Sachiko , Friesen Sarah K. , Ban Natalie C. , Hunter Karen L. , Pena Angelica , Holdsworth Amber , Martone Rebecca 
Published: February 2024

Marine protected area (MPAs) networks can buffer marine ecosystems from the impacts of climate change by allowing species to redistribute as conditions change and by reducing other stressors. There are, however, few examples where climate change has been considered in MPA network design. In this paper, we assess how climate change considerations were integrated into the design of a newly released MPA network in the Northern Shelf Bioregion in British Columbia, Canada, and then evaluate the resulting network against projected physical and biogeochemical changes and biological responses. We found that representation, replication, and size and spacing recommendations integrated into the design phase were met in most cases. Furthermore, despite varying degrees of projected changes in temperature, dissolved oxygen, and aragonite saturation across the MPA network, suitable habitat for demersal fish species is projected to remain in the network despite some redistribution among sites. We also found that mid-depth MPAs are particularly important for persistence, as fish are projected to move deeper to avoid warming in shallower areas. Our results highlight that a representative MPA network with adequate replication, that incorporates areas of varying climate change trajectory, should buffer against the impacts of climate change.
FATP5 Is Indispensable for the Growth of Intrahepatic Cholangiocarcinoma
Authors: Shihadih Diyala , Wang Xue , Zushin Peter-James H. , Khodakivskyi Pavlo , Park Hyo Min , Tso Emily , Shiblak Jena , Misic Angela , Louie Sharon M. , Ward Catherine , Hellerstein Marc , Nomura Daniel K. , Goun Elena , Urigo Francesco , Calvisi Diego F. , Chen Xin , Stahl Andreas 
Published: February 2024

Abstract

Altered lipid metabolism is a common hallmark of various cancers, including intrahepatic cholangiocarcinoma (ICC), a highly lethal carcinoma that lacks effective treatment options. To elucidate the lipid metabolism changes in ICC, we coupled the expression of the firefly luciferase gene (FFL) to AKT1 (AKT-FFL) via an IRES linker, and then hydrodynamically injected mice with AKT-FFL and Notch1 intracellular cytoplasmic domain (NICD) to establish a luciferase-positive ICC model. This model not only enabled us to monitor and quantify tumor growth by injecting the mice with luciferin, but also allowed us to assess the fatty acid uptake rate by injecting the mice with free fatty acid luciferin (FFA-Luc). The ICC model exhibited robust uptake of exogenous fatty acids compared with the HCC model induced by AKT-FFL/ neuroblastoma Ras (Ras). Lipidomics analysis showed a dramatically higher level of fatty acid in ICC, further supporting the increased fatty acids uptake. Mechanistic studies identified FATP5 as the predominant mediator of fatty acid uptake required for ICC growth using Fatp5 knockout mice and AAV-based shRNA silencing of Fatp5. Our study discovered a novel therapeutic target for the treatment of ICC and shed light on the contributions of lipid metabolism to ICC development.

Implications:
This study provides the first in vivo evidence that FATP5 is a potential therapeutic target for treating ICC.
Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils
Authors: Fetit Rana , McLaren Alistair S. , White Mark , Mills Megan L. , Falconer John , Cortes-Lavaud Xabier , Gilroy Kathryn , Lannagan Tamsin R.M. , Ridgway Rachel A. , Nixon Colin , Naiker Varushka , Njunge Renee , Clarke Cassie J. , Whyte Declan , Kirschner Kristina , Jackstadt Rene , Norman Jim , Carlin Leo M. , Campbell Andrew D. , Sansom Owen J. , Steele Colin W. 
Published: February 2024

Abstract

Neutrophils are a highly heterogeneous cellular population. However, a thorough examination of the different transcriptional neutrophil states between health and malignancy has not been performed. We utilized single-cell RNA sequencing of human and murine datasets, both publicly available and independently generated, to identify neutrophil transcriptomic subtypes and developmental lineages in health and malignancy. Datasets of lung, breast, and colorectal cancer were integrated to establish and validate neutrophil gene signatures. Pseudotime analysis was used to identify genes driving neutrophil development from health to cancer. Finally, ligand–receptor interactions and signaling pathways between neutrophils and other immune cell populations in primary colorectal cancer and metastatic colorectal cancer were investigated. We define two main neutrophil subtypes in primary tumors: an activated subtype sharing the transcriptomic signatures of healthy neutrophils; and a tumor-specific subtype. This signature is conserved in murine and human cancer, across different tumor types. In colorectal cancer metastases, neutrophils are more heterogeneous, exhibiting additional transcriptomic subtypes. Pseudotime analysis implicates IL1β/CXCL8/CXCR2 axis in the progression of neutrophils from health to cancer and metastasis, with effects on T-cell effector function. Functional analysis of neutrophil-tumoroid cocultures and T-cell proliferation assays using orthotopic metastatic mouse models lacking Cxcr2 in neutrophils support our transcriptional analysis. We propose that the emergence of metastatic-specific neutrophil subtypes is driven by the IL1β/CXCL8/CXCR2 axis, with the evolution of different transcriptomic signals that impair T-cell function at the metastatic site. Thus, a better understanding of neutrophil transcriptomic programming could optimize immunotherapeutic interventions into early and late interventions, targeting different neutrophil states.

Significance:
We identify two recurring neutrophil populations and demonstrate their staged evolution from health to malignancy through the IL1β/CXCL8/CXCR2 axis, allowing for immunotherapeutic neutrophil-targeting approaches to counteract immunosuppressive subtypes that emerge in metastasis.
Addressing the Binning Problem in Calibration Assessment through Scalar Annotations
Authors: Jiang Zhengping , Liu Anqi , Durme Benjamnin Van 
Published: February 2024

Abstract
Computational linguistics models commonly target the prediction of discrete—categorical—labels. When assessing how well-calibrated these model predictions are, popular evaluation schemes require practitioners to manually determine a binning scheme: grouping labels into bins to approximate true label posterior. The problem is that these metrics are sensitive to binning decisions. We consider two solutions to the binning problem that apply at the stage of data annotation: collecting either distributed (redundant) labels or direct scalar value assignment.
In this paper, we show that although both approaches address the binning problem by evaluating instance-level calibration, direct scalar assignment is significantly more cost-effective. We provide theoretical analysis and empirical evidence to support our proposal for dataset creators to adopt scalar annotation protocols to enable a higher-quality assessment of model calibration.
North Atlantic Ocean–Originated Multicentennial Oscillation of the AMOC: A Coupled Model Study
Authors: Yang Kunpeng , Yang Haijun , Li Yang , Zhang Qiong 
Published: February 2024

Abstract
Using a CESM1 control simulation, we conduct a follow-up study to advance our earlier theoretical research on the multicentennial oscillation (MCO) of the Atlantic meridional overturning circulation (AMOC). The modeled AMOC MCO primarily arises from internal oceanic processes in the North Atlantic, potentially representing a North Atlantic Ocean–originated mode of AMOC multicentennial variability (MCV) in reality. Specifically, this AMOC MCO is mainly driven by salinity variation in the subpolar upper North Atlantic, which dominates local density variation. Salinity anomaly in the subpolar upper ocean is enhanced by the well-known positive salinity advection feedback that is realized through anomalous advection in the subtropical to subpolar upper ocean. Meanwhile, mean advection moves salinity anomaly in the subtropical intermediate ocean northward, weakening the subpolar upper salinity anomaly and leading to its phase change. The salinity anomalies have a clear three-dimensional life cycle around the North Atlantic. The mechanism and time scale of the modeled AMOC MCO are consistent with our earlier theoretical studies. In the theoretical model, artificially deactivating either the anomalous or mean advection in the AMOC upper branch prevents it from exhibiting AMOC MCO, underscoring the indispensability of both the anomalous and mean advections in this North Atlantic Ocean–originated AMOC MCO. In our coupled model simulation, the South Atlantic and Southern Oceans do not exhibit variabilities synchronous with the AMOC MCO; the Arctic Ocean’s contribution to the subpolar upper salinity anomaly is much weaker than the North Atlantic. Hence, this North Atlantic Ocean–originated AMOC MCO is distinct from the previously proposed Southern Ocean–originated and Arctic Ocean–originated AMOC MCOs.
A molecular circuit linking the BCR to the NAD biosynthetic enzyme NAMPT is an actionable target in Richter syndrome
Authors: Messana Vincenzo G. , Fascì Amelia , Vitale Nicoletta , Micillo Matilde , Rovere Matteo , Pesce Noemi A. , Martines Claudio , Efremov Dimitar G. , Vaisitti Tiziana , Deaglio Silvia 
Published: February 2024

Abstract
This works defines, to the best of our knowledge, for the first time a molecular circuit connecting nicotinamide mononucleoside phosphoribosyl transferase (NAMPT) activity to the B-cell receptor (BCR) pathway. Using 4 distinct xenograft models derived from patients with Richter syndrome (RS-PDX), we show that BCR cross-linking results in transcriptional activation of the nicotinamide adenine dinucleotide (NAD) biosynthetic enzyme NAMPT, with increased protein expression, in turn, positively affecting global cellular NAD levels and sirtuins activity. NAMPT blockade, by using the novel OT-82 inhibitor in combination with either BTK or PI3K inhibitors (BTKi or PI3Ki), induces rapid and potent apoptotic responses in all 4 models, independently of their mutational profile and the expression of the other NAD biosynthetic enzymes, including nicotinate phosphoribosyltransferase. The connecting link in the circuit is represented by AKT that is both tyrosine- and serine-phosphorylated by PI3K and deacetylated by sirtuin 1 and 2 to obtain full kinase activation. Acetylation (ie, inhibition) of AKT after OT-82 administration was shown by 2-dimensional gel electrophoresis and immunoprecipitation. Consistently, pharmacological inhibition or silencing of sirtuin 1 and 2 impairs AKT activation and induces apoptosis of RS cells in combination with PI3Ki or BTKi. Lastly, treatment of RS-PDX mice with the combination of PI3Ki and OT-82 results in significant inhibition of tumor growth, with evidence of in vivo activation of apoptosis. Collectively, these data highlight a novel application for NAMPT inhibitors in combination with BTKi or PI3Ki in aggressive lymphomas.
Serum fibroblast growth factor-2 levels complement vital biomarkers for diagnosing heart failure
Authors: Yu Z. L. , Cai Z. H. , Zheng J. T. , Jiang H. Y. , Zhou Y. Q. , Wong N. K. , Fu H. B. , Hong X. B. 
Published: February 2024

Abstract
Background
Early diagnosis of atrial fibrillation is important as it is crucial for improving patient outcomes. Fibroblast growth factor-2 (FGF2) may serve as a diagnostic biomarker for heart failure due to its ability to promote cardiac fibrosis and hypertrophy; however, the relationship between FGF2 concentration and heart failure is unclear. Therefore, this study aimed to explore whether FGF2 could aid in distinguishing patients with heart failure from healthy controls and those with dyspnea without heart failure. Additionally, to evaluate the possible correlation between serum FGF2 levels and its diagnostic parameters in patients with heart failure.

Methods
Plasma FGF2 concentration was measured in 114 patients with a complaint of dyspnea (enrolled in the study between January 2022 and August 2022). Based on heart failure diagnosis, the patients were assigned to three groups, as follows: heart failure (n = 80), non-heart-failure dyspnea (n = 34), and healthy controls (n = 36), following physical examination. Possible correlations between serum FGF2 levels and other prognostic parameters in patients with heart failure were analyzed.

Results
Serum FGF2 levels were higher in patients with heart failure (125.60 [88.95, 183.40] pg/mL) than in those with non-heart-failure dyspnea (65.30 [28.85, 78.95] pg/mL) and healthy controls (78.90 [60.80, 87.20] pg/mL) (p < 0.001). Receiver operating characteristic curve analysis identified FGF2 concentration as a significant predictor in heart failure diagnosis, with an area under the curve of 0.8693 (p < 0.0001). Importantly, in the heart failure group, serum FGF2 concentrations correlated with key prognostic parameters for heart failure, such as reduced left ventricular ejection fraction and elevated serum levels of N-terminal pro-B-type natriuretic peptide.

Conclusions
Elevated serum FGF2 level is strongly associated with an increased risk of heart failure and could serve as a useful biomarker to complement vital diagnostic parameters for heart failure.