bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymmetric dimethylation of Ribosomal S6 Kinase 2 regulates its cellular localisation and pro-survival function
Authors: Khalil Mahmoud I. , Ismail Heba M. , Panasyuk Ganna , Gout Ivan , Pardo Olivier E. 
Published: October 2022

AbstractRibosomal S6 Kinases (S6Ks) are critical regulators of cell growth, homeostasis, and survival, with dysregulation of these kinases being associated with various malignancies. While S6K1 has been extensively studied, S6K2 has been neglected despite its reported involvement in cancer progression. Protein arginine methylation is a widespread post-translational modification regulating a plethora of biological responses in mammalian cells. Here we report that p54-S6K2 is asymmetrically dimethylated at Arg-475 and Arg-477, two conserved residues within the AT-hook motif of the S6K2 family and some AT-hook-containing proteins. We demonstrate that PRMT1, PRMT3, and PRMT6 bind to and methylate S6K2in vitroandin vivo. This methylation localises S6K2 to the nucleus where it rescues cells from starvation-induced cell death. Taken together, our findings highlight a novel mechanism regulating the biological function of p54-S6K2 that may be relevant to cancer where Arg-methylation is often found elevated.
Distinct contact guidance mechanisms in single endothelial cells and in monolayers
Authors: Leclech Claire , Krishnamurthy Apoorvaa , Muller Laurent , Barakat Abdul I. 
Published: October 2022

AbstractIn many tissues, cell shape and orientation are controlled by a combination of internal and external biophysical cues. Anisotropic substrate topography is a ubiquitous cue that leads to cellular elongation and alignment, a process termed contact guidance, whose underlying mechanisms remain incompletely understood. Additionally, whether contact guidance responses are similar in single cells and in cellular monolayers is unknown. Here, we address these questions in vascular endothelial cells (ECs) thatin vivoform a monolayer that lines blood vessels. Culturing single ECs on microgrooved substrates that constitute an idealized mimic of anisotropic basement membrane topography elicits a strong, groove depth-dependent contact guidance response. Interestingly, this response is greatly attenuated in confluent monolayers. While contact guidance in single cells is principally driven by persistence bias of cell protrusions in the direction of the grooves and is surprisingly insensitive to actin stress fiber disruption, cell shape and alignment in dense EC monolayers are driven by the organization of the basement membrane secreted by the cells, which leads to a loss of interaction with the microgrooves. The findings of distinct contact guidance mechanisms in single ECs and in EC monolayers promise to inform strategies aimed at designing topographically patterned endovascular devices.
A Novel Biosensor Reveals Dynamic Changes of C-di-GMP in Differentiating Cells with Ultra-High Temporal Resolution
Authors: Kaczmarczyk Andreas , van Vliet Simon , Jakob Roman Peter , Reinders Alberto , Klotz Alexander , Maier Timm , Jenal Urs 
Published: October 2022

ABSTRACTCyclic diguanylate (c-di-GMP) is a ubiquitous second messenger that regulates a wide range of biological processes in bacteria, including motility, surface attachment, virulence and persistence. The regulatory networks controlling c-di-GMP are generally complex and understudied. This is largely due to a lack of appropriate tools to monitor dynamic changes of c-di-GMP concentrationsin vivoin a non-invasive manner. Here, we develop a genetically-encoded ratiometric c-di-GMP biosensor, called cdGreen2, by applying a powerful directed evolution approach based on iterative fluorescence-activated cell sorting (FACS) under alternating c-di-GMP regimes. We demonstrate that cdGreen2 can robustly track c-di-GMP dynamics in live cells with ultra-high temporal resolution over multiple generations. To validate its exquisite diagnostic power, we utilize cdGreen2 to dissect the regulatory networks driving bimodal developmental programs in the environmental model organismCaulobacter crescentusand the human pathogenPseudomonas aeruginosa. These studies disclose the molecular determinants governing cell cycle-dependent c-di-GMP oscillations inC. crescentusand surface-induced c-di-GMP asymmetry inP. aeruginosa. The sensitivity and versatility of cdGreen2 will help unveil c-di-GMP dynamics in a wide range of organisms with unprecedented temporal resolution. The simple, yet powerful design principles underlying cdGreen2 will serve as a blueprint for the development of similar, orthogonal biosensors for other signaling molecules, metabolites or antibiotics, paving the way to uncover the complex interplay of small molecule-based networks with unprecedented spatiotemporal resolution.
Abundant Aβ fibrils in ultracentrifugal supernatants of aqueous extracts from Alzheimer’s disease brains
Authors: Stern Andrew M. , Yang Yang , Meunier Angela L. , Liu Wen , Cai Yuqi , Ericsson Maria , Liu Lei , Goedert Michel , Scheres Sjors H. W. , Selkoe Dennis J. 
Published: October 2022

AbstractSoluble aggregates of amyloid-β (Aβ), often called oligomers, are believed to be principal drivers of neurotoxicity, spreading of pathology, and symptoms in Alzheimer’s disease (AD), but little is known about their structures in human brain. Aβ oligomers have been defined as aggregates found in supernatants following ultracentrifugation of aqueous extracts. We now report the unexpected presence of abundant Aβ fibrils in high-speed supernatants from AD brains that were extracted by soaking in aqueous buffer. The fibrils did not appear to form during extract preparation, and their numbers by EM correlated with ELISA quantification of aggregated Aβ42. Cryo-EM structures of Aβ fibrils from aqueous extracts were identical to those from sarkosyl-insoluble AD brain homogenates. The fibrils in aqueous extracts were immunolabeled by lecanemab, an Aβ aggregate-directed antibody reported to improve cognitive outcomes in AD. We conclude that Aβ fibrils are abundant in aqueous extracts from AD brains and have the same structures as those from amyloid plaques. These findings have implications for understanding the nature of Aβ oligomers and for designing oligomer-preferring therapeutic antibodies.
The Calpain-7 protease functions together with the ESCRT-III protein IST1 within the midbody to regulate the timing and completion of abscission
Authors: Paine Elliott L. , Skalicky Jack J. , Whitby Frank G. , Mackay Douglas R. , Ullman Katharine S. , Hill Christopher P. , Sundquist Wesley I. 
Published: October 2022

AbstractThe Endosomal Sorting Complexes Required for Transport (ESCRT) machinery mediates the membrane fission step that completes cytokinetic abscission and separates dividing cells. Filaments composed of ESCRT-III subunits constrict membranes of the intercellular bridge midbody to the abscission point. These filaments also bind and recruit cofactors whose activities help execute abscission and/or delay abscission timing in response to mitotic errors via the NoCut/Abscission checkpoint. We previously showed that the ESCRT-III subunit IST1 binds the cysteine protease CAPN7 (Calpain-7) and that CAPN7 is required for both efficient abscission and NoCut checkpoint maintenance (Wenzelet al., 2022). Here, we report biochemical and crystallographic studies showing that the tandem MIT domains of CAPN7 bind simultaneously to two distinct IST1 MIT interaction motifs. Structure-guided point mutations in either CAPN7 MIT domain disrupted IST1 binding in vitro and in cells, and depletion/rescue experiments showed that the CAPN7-IST1 interaction is required for: 1) CAPN7 recruitment to midbodies, 2) efficient abscission, and 3) NoCut checkpoint arrest. CAPN7 proteolytic activity is also required for abscission and checkpoint maintenance. Hence, IST1 recruits CAPN7 to midbodies, where its proteolytic activity is required to regulate and complete abscission.
The MTIST platform: a microbiome time series inference standardized test simulation, dataset, and scoring systems
Authors: Hussey Grant A. , Zhang Chenzhen , Sullivan Alexis P. , Fenyö David , Schluter Jonas 
Published: October 2022

AbstractThe human gut microbiome is promising therapeutic target, but development of interventions is hampered by limited understanding of the microbial ecosystem. Therefore, recent years have seen a surge in the engineering of inference algorithms seeking to unravel rules of ecological interactions from metagenomic data. Research groups score algorithmic performance in a variety of different ways, however, there exists no unified framework to score and rank each inference approach. The machine learning field presents a useful solution to this issue: a unified set of validation data and accompanying scoring metric. Here, we present MTIST: a platform for benchmarking microbial ecosystem inference tools. We use a generalized Lotka-Volterra framework to simulate microbial abundances over time, akin to what would be obtained by quantitative metagenomic sequencing studies or lab experiments, to generate a massivein silicotraining dataset (MTIST) for algorithmic validation, as well as an “ecological sign” score (ES score) to rate them. MTIST comprises 24,570 time series of microbial abundance data packaged into 648 datasets. Together, the MTIST dataset and the ES score serve as a platform to develop and compare microbiome ecosystem inference approaches.
MagPEG: a complete extracellular vesicle isolation/analysis solution
Authors: Sun Li , York Sara , Pate Brandon , Zhang Yanping , Meckes David G. 
Published: October 2022

AbstractCurrent extracellular vesicle (EV) isolation methods depend on large expensive equipment like ultracentrifuges and are laborious and time consuming. There is also currently no method available for high throughput isolation to meet clinical demands. Here, we present a method that combines our previous published ExtraPEG method and magnetic beads. Western blot and nanoparticle tracking analysis (NTA) of the purified EVs revealed higher or equivalent recovery and purity with this method compared to ExtraPEG or size exclusion chromatography (SEC) methods. With this newly developed workflow and automated liquid handling instrument, we have successfully isolated up to 96 EV samples from 5 µL pre-cleared serum in 45 minutes. Moreover, DNA / small RNA / protein purification and profiling steps could be seamlessly integrated into the isolation workflow. To profile EV protein markers, EVs were lysed from the binding step and covalently bound to the surface of the beads. TotalSeq or ELISA antibody can be applied with under a standard protocol. With this extended protocol, researchers can easily complete EV isolation and protein profiling experiment within 8 hours. Taken together, we provide a high throughput method for EV isolation and molecular analyses that may be used for sensitive biomarker detection from biological fluids.
The Opto-inflammasome in zebrafish: a tool to study cell and tissue responses to speck formation and cell death
Authors: de Carvalho Eva Hasel , Dharmadhikari Shivani , Shkarina Kateryna , Xiong Jingwei Rachel , Reversade Bruno , Broz Petr , Leptin Maria 
Published: October 2022

The inflammasome is a conserved system for the intracellular detection of danger or pathogen signals. By forming a large intracellular multiprotein signaling platform, it activates downstream effectors that initiate a rapid necrotic programmed cell death (PCD) termed pyroptosis and activation and secretion of pro-inflammatory cytokines to warn and activate surrounding cells. However, inflammasome activation is difficult to control on a single-cell level using canonical triggers. We constructed Opto-Asc, a light-responsive form of the inflammasome adaptor protein ASC (Apoptosis-Associated Speck-Like Protein Containing a CARD) which allows tight control of inflammasome formationin vivo.We introduced a cassette of this construct under the control of a heat shock element into zebrafish in which we can now induce Asc inflammasome (speck) formation in single cells of the skin.We find that cell death resulting from Asc speck formation is morphological distinct from apoptosis in periderm but not in basal cells. Asc induced PCD in can lead to apical or basal extrusion from the periderm. The apical extrusion in periderm cells depends on Caspb but and triggers a strong Ca2+signaling response in nearby cells.
Understanding social media users' engagement intention toward emergency information: the role of experience and information usefulness in a reciprocity framework
Authors: Li Yixiao , Hu Yaoqi , Yang Shuiqing 
Published: October 2022

PurposeThe aim of this study is to investigate how social media users' experience of seeking emergency information affects their engagement intention toward emergency information with a reciprocity framework integrated with information adoption model.Design/methodology/approachDrawing on reciprocity theory, indebtedness theory, and information adoption model, an integrative research model is developed. This study employs a questionnaire survey to collect data of 325 social media users in China. Structural equation modeling analyses are conducted to test the proposed theoretical model.FindingsSocial media users' experience of seeking emergency information has a strong effect on their perceived information usefulness and indebtedness, while perceived information usefulness further influences community norm, indebtedness, and engagement intention. The authors also found that perceived information usefulness mediates the relationships between experience of seeking emergency information and community norm/indebtedness.Originality/valueThis study offers a new perspective to explain social media users' engagement intention in the diffusion of emergency information. This study contributes to the literature by extending the theoretical framework of reciprocity and applying it to the context of emergency information diffusion. The findings of this study could benefit the practitioners who wish to leverage social media tools for emergency response purposes.
Searching while sick: How does disease affect foraging decisions and contact rates?
Authors: Tillman Francis E. , Adelman James S. 
Published: October 2022

AbstractInfection often changes an animal's motivation or ability to forage, which should alter rates of contact with uninfected hosts. However, links are likely complex and remain poorly understood. Here, we explore relationships among infection, foraging decisions and contact rates and how these could interact with ecological factors to drive pathogen transmission.Under optimal foraging theory, animals should gather the highest quality resources from a patch, leaving only once the cost of continued foraging outweighs the amount of energy gained. However, the ability to locate and evaluate resources will vary with many factors, including disease, temperature and habitat fragmentation. Although modelling suggests that such variation in foraging decisions can alter contact rates among infected and uninfected hosts, and thus transmission and evolution of infectious agents, empirical studies have only begun to test the direction and strength of such relationships.We propose that foraging behaviour will often change with infection, thereby affecting contact rates, because of sickness behaviours, self‐medication, parasite manipulation of the host and nonadaptive behavioural responses to infection. We recommend that future studies empirically test how such associations vary with ambient temperature and habitat fragmentation, as human activity continues to alter these environmental pressures. Furthermore, we suggest that such relationships among infection, foraging and environmental factors could help shape not only population‐level disease dynamics, but also surrounding ecological communities.By revealing how environmental factors impact such links, we can improve our understanding and prediction of animal disease dynamics in the face of changing ecosystems.Read the freePlain Language Summaryfor this article on the Journal blog.
Illness wellness scale: novel grading system for performance status of patients under surgical care
Authors: Kumar Arun , Puri Gopal , Rathore Yashwant Singh , Chumber Sunil , Trikha Anjan , Ranjan Piyush , Kataria Kamal , Bhattacharjee Hemanga K. 
Published: October 2022

AbstractBackgroundGrading the illness using clinical parameters is essential for the daily progress of inpatients. Existing systems do not incorporate these parameters holistically. The study was designed to internally validate the illness wellness scale, based upon clinical assessment of the patients requiring surgical care, for their risk stratification and uniformity of communication between health care providers.MethodsProspective observational study conducted at a tertiary care hospital. An expert panel devised the scale, and it was modified after feedback from 100 health care providers. A total of 210 patients (150 for internal validation and 60 for inter‐observer variability) who required care under the department of surgical disciplines were enrolled. This included patients presenting to surgery OPD, admitted to COVID/non‐COVID surgical wards and ICUs, aged ≥16 years.ResultsThe response rate of the final illness wellness scale was 95% with 86% positive feedback and a mean of 1.7 on the Likert scale for ease of use (one being very easy and five being difficult). It showed excellent consistency and minimal inter‐observer variability with the intra‐class correlation coefficient (ICC) above 0.9. In the internal validation cohort (n = 150), univariate and multivariable analysis of factors affecting mortality revealed that categorical risk stratification, age ≥ 60 years, presence or absence of co‐morbidities especially hypertension and chronic kidney disease significantly affect mortality.ConclusionsThe Illness wellness scale is an effective tool for uniformly communicating between health care professionals and is also a strong predictor of risk stratification and mortality in patients requiring surgical care.
Scale morphological variation across the flank in four Tonguefishes species collected from the Gulf of Oman (Pleuronectiforms; Cynoglossidae)
Authors: Kishipour Sanaz , Teimori Azad , Askari Hesni Majid , Motamedi Mina 
Published: October 2022

AbstractThe scale morphology of pleuronectiforms in the Gulf of Oman remains insufficiently known. This study used light microscopy and morphological analysis to examine scale variation across the flank of four Tonguefishes species; Cynoglossus arel, C. bilineatus, C. lingua, and C. puncticeps. Scales were extracted from six flank regions, three on the eyed and blind sides, respectively. The most differentiated species was C. arel, which showed significant differences in four size variables in five regions. In Cynoglossus arel and C. lingua, the scales of the eyed side were ctenoid, and those scales from the blind side were cycloid; C. puncticeps have ctenoid scales on both flank sides and C. bilineatus has cycloid scales on both sides. All species' scales on the blind side have fewer ctenial spines (except in C. bilineatus). This study indicated that scale morphology demonstrated considerable variation among the flank regions of the examined species. As a result, the scales from the head and the trunk regions of the eyed side and the scales from the head region of the blind side have a good power of species separation in this family.
Effect of mitral valve transcatheter edge‐to‐edge repair on indices of left atrial performance in chronic mitral regurgitation
Authors: Biersmith Michael , Orsinelli David A. , Harfi Thura T. , Lilly Scott , Boudoulas Konstantinos Dean 
Published: October 2022

AbstractIntroductionEffect of transcatheter edge‐to‐edge repair (TEER) using MitraClip in patients with mitral regurgitation (MR) on left atrial (LA) kinetic energy (LAKE), an index of LA work, and LA strain, a measure of LA performance, have not been well defined.MethodsPatients with chronic primary or secondary 3+ or 4+ MR were analyzed pre‐ and post‐TEER using MitraClip. LAKE was determined by echocardiography using LA stroke volume and A‐wave velocity. Peak atrial longitudinal strain (PALS), peak atrial strain in early diastole, and peak atrial contraction strain (PACS) were obtained by speckle tracking echocardiography.ResultsThirty‐nine patients undergoing TEER with MitraClip were screened, 12 met criteria for analysis (9 primary and 3 secondary MR). Compared to pre‐TEER, there was a significant increase post‐TEER in LAKE (71.0 ± 64.1 vs. 177.5 ± 167.9 dyne·cm·103, respectively; p = .008) and Doppler transmitral A‐wave velocity (87.8 ± 41.4 vs. 138.5 ± 43.7 cm/s, respectively; p < .001); LA stroke volume did not change significantly. Mitral valve mean gradient significantly increased post‐TEER compared to pre‐TEER (5.7 ± 2.1 vs. 3.3 ± 2.1 mmHg, respectively; p = .01). There was a trend toward decrease in PALS post‐TEER compared to pre‐TEER (16.2 ± 4.8 vs. 20.7 ± 9.9%, respectively; p = .05). Peak atrial strain in early diastole significantly decreased post‐TEER compared to pre‐TEER (7.2 ± 3.0 vs. 14.1 ± 7.2%; respectively, p < .001), while PACS did not significantly change (9.1 ± 3.5 vs. 6.7 ± 5.2%, respectively; p = .07).ConclusionIn patients with chronic MR, LAKE increases after TEER with MitraClip driven by an increase in LA emptying velocities. Changes were also seen in LA strain with MitraClip. These procedurally induced changes due to mild mitral stenosis may have clinical implications.
The great margin call: The role of leverage in the 1929 Wall Street crash
Authors: Borowiecki Karol Jan , Dzieliński Michał , Tepper Alexander 
Published: October 2022

AbstractThe reasons for the 1929 Wall Street crash and why it occurred at the particular time that it did are still debated among economic historians. We contribute to this debate by building on a new model, which provides a measure of the financial system's potential for financial crises. The evidence suggests that a tightening of margin requirements in the first nine months of 1929 combined with price declines in September and early October caused enough investors to become constrained that the market was tipped into instability, triggering the sudden crash of October and November.
Leaf habit affects the distribution of drought sensitivity but not water transport efficiency in the tropics
Authors: Vargas G. German , Kunert Norbert , Hammond William M. , Berry Z. Carter , Werden Leland K. , Smith‐Martin Chris M. , Wolfe Brett T. , Toro Laura , Mondragón‐Botero Ariadna , Pinto‐Ledezma Jesús N. , Schwartz Naomi B. , Uriarte María , Sack Lawren , Anderson‐Teixeira Kristina J. , Powers Jennifer S. 
Published: October 2022

AbstractConsidering the global intensification of aridity in tropical biomes due to climate change, we need to understand what shapes the distribution of drought sensitivity in tropical plants. We conducted a pantropical data synthesis representing 1117 species to test whether xylem‐specific hydraulic conductivity (KS), water potential at leaf turgor loss (ΨTLP) and water potential at 50% loss of KS(ΨP50) varied along climate gradients. The ΨTLPand ΨP50increased with climatic moisture only for evergreen species, but KSdid not. Species with high ΨTLPand ΨP50values were associated with both dry and wet environments. However, drought‐deciduous species showed high ΨTLPand ΨP50values regardless of water availability, whereas evergreen species only in wet environments. All three traits showed a weak phylogenetic signal and a short half‐life. These results suggest strong environmental controls on trait variance, which in turn is modulated by leaf habit along climatic moisture gradients in the tropics.