bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical exercise ameliorates age‐related deterioration of skeletal muscle and mortality by activating Pten‐related pathways in Drosophila on a high‐salt diet
Authors: Hou Wen‐qi , Wen Deng‐tai , Zhong Qi , Mo Lan , Wang Shuo , Yin Xin‐yuan , Ma Xing‐feng 
Published: November 2023

AbstractThe phosphatase and tensin congeners (Pten) gene affects cell growth, cell proliferation, and rearrangement of connections, and it is closely related to cellular senescence, but it remains unclear the role of muscle‐Pten gene in exercise against age‐related deterioration in skeletal muscle and mortality induced by a high‐salt diet (HSD). In here, overexpression and knockdown of muscle Pten gene were constructed by building MhcGAL4/PtenUAS‐overexpression and MhcGAL4/PtenUAS‐RNAi system in flies, and flies were given exercise training and a HSD for 2 weeks. The results showed that muscle Pten knockdown significantly reduced the climbing speed, climbing endurance, GPX activity, and the expression of Pten, Sirt1, PGC‐1α genes, and it significantly increased the expression of Akt and ROS level, and impaired myofibril and mitochondria of aged skeletal muscle. Pten knockdown prevented exercise from countering the HSD‐induced age‐related deterioration of skeletal muscle. Pten overexpression has the opposite effect on skeletal muscle aging when compared to it knockdown, and it promoted exercise against HSD‐induced age‐related deterioration of skeletal muscle. Pten overexpression significantly increased lifespan, but its knockdown significantly decreased lifespan of flies. Thus, current results confirmed that differential expression of muscle Pten gene played an important role in regulating skeletal muscle aging and lifespan, and it also affected the adaptability of aging skeletal muscle to physical exercise since it determined the activity of muscle Pten/Akt pathway and Pten/Sirt1/PGC‐1α pathway.
Clinical Efficacy of Gadobutrol: Review of Over 25 Years of Use Exceeding 100 Million Administrations
Authors: Endrikat Jan , Gutberlet Matthias , Barkhausen Jörg , Schöckel Laura , Bhatti Aasia , Harz Cornelia , Hoffmann Karl-Titus 
Published: November 2023

Background
Gadobutrol has been administered more than 100 million times worldwide, since February 1998, that is, over the last 25 years. Numerous clinical studies in a broad range of indications document the long-term experience with gadobutrol.

Objective
The aim of this study was to provide a literature-based overview on gadobutrol's efficacy in 9 approved indications and use in children.

Materials and Methods
Efficacy results in patients of all age groups including sensitivity, specificity, accuracy, and positive/negative predictive values were identified by a systematic literature search on Embase until December 31, 2022. Nine approved indications were considered: central nervous system (CNS), magnetic resonance angiography (MRA), breast, heart, prostate, kidney, liver, musculoskeletal, whole body, and various indications in children.

Results
Sixty-five publications (10 phase III, 2 phase IV, 53 investigator-initiated studies) reported diagnostic efficacy results obtained from 7806 patients including 271 children, at 369 centers worldwide. Indication-specific sensitivity ranges were 59%–98% (CNS), 53%–100% (MRA), 80%–100% (breast), 64%–90% (heart), 64%–96% (prostate), 71–85 (kidney), 79%–100% (liver), 53%–98% (musculoskeletal), and 78%–100% (children). Indication-specific specificity ranges were 75%–100% (CNS), 64%–99% (MRA), 58%–98% (breast), and 47%–100% (heart).

Conclusions
The evaluated body of evidence, consisting of 65 studies with 7806 patients, including 271 children and 7535 adults, showed that gadobutrol is an efficacious magnetic resonance imaging contrast agent for all age groups in various approved indications throughout the whole body.
Perturbation of tonoplast sucrose transport alters carbohydrate utilization for seasonal growth and defense metabolism in coppiced poplar
Authors: Tuma Trevor T. , Nyamdari Batbayar , Hsieh Chen , Chen Yen-Ho , Harding Scott A. , Tsai Chung-Jui 
Published: November 2023

AbstractNon-structural carbohydrate reserves of stems and roots underpin overall tree fitness. These reserves also contribute to productivity under short-rotation management practices such as coppicing for bioenergy. While sucrose and starch comprise the predominant carbohydrate reserves ofPopulus, utilization is understood primarily in terms of starch turnover. The tonoplast sucrose transport protein SUT4 modulates sucrose export from source leaves to distant sinks during photoautotrophic growth, but the possibility of its involvement in remobilizing carbohydrates from sinks during heterotrophic growth has not been explored. Here, we usedPtaSUT4-knockout mutants ofPopulus tremula × P. alba(INRA 717-1B4) in winter (cool) and summer (warm) glasshouse coppicing experiments to strain carbon demand and test for SUT4 involvement in reserve utilization. We show that epicormic bud emergence, subsequent growth, and xylem hexose increases were delayed or reduced insut4mutants following lower temperature ‘winter’ coppicing. Depletion of stem reserves during post-coppice regrowth was not impaired insut4, butsut4winter maintenance costs may have been higher in metabolic terms. Bark accrual of abundant defense metabolites, including salicinoids, chlorogenic acids, and flavonoid products, was prioritized in the summer, but attenuated insut4mutants. Summer sprout growth was not reduced insut4compared to controls. Together, our results point to shifting priorities for SUT4 modulation of seasonal trade-offs between growth and other priorities in the stem and emerging buds during reserve utilization inPopulus.
Virological characteristics of the SARS-CoV-2 Omicron HK.3 variant harboring the “FLip” substitution
Authors: Kosugi Yusuke , Plianchaisuk Arnon , Putri Olivia , Uriu Keiya , Kaku Yu , Hinay Alfredo A. , Chen Luo , Kuramochi Jin , Sadamasu Kenji , Yoshimura Kazuhisa , Asakura Hiroyuki , Nagashima Mami ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Ito Jumpei , Sato Kei 
Published: November 2023

AbstractIn November 2023, SARS-CoV-2 XBB descendants, including EG.5.1 (XBB.1.9.2.5.1), the currently predominant lineage, are circulating worldwide according to Nextstrain. EG.5.1 has a characteristic amino acid substitution in the spike protein (S), S:F456L, which contributes to its escape from humoral immunity. EG.5.1 has further evolved, and its descendant lineage harboring S:L455F (i.e., EG.5.1+S:L455F) emerged and was named HK.3 (XBB.1.9.2.5.1.1.3). HK.3 was initially discovered in East Asia and is rapidly spreading worldwide. Notably, the XBB subvariants bearing both S:L455F and S:F456L substitutions, including HK.3, are called the “FLip” variants. These FLip variants, such as JG.3 (XBB.1.9.2.5.1.3.3), JF.1 (XBB.1.16.6.1) and GK.3 (XBB.1.5.70.3), have emerged convergently, suggesting that the acquisition of these two substitutions confers a growth advantage to XBB in the human population. Here, we investigated the virological properties of HK.3 as a representative of the FLip variants.
Oxidation of hemoglobin in the lung parenchyma facilitates the differentiation of pneumococci into encapsulated bacteria
Authors: Alibayov Babek , Scasny Anna , Vidal Ana G. Jop , Murin Landon , Wong Sandy , Edwards Kristin S. , Eichembaun Zehava , Punshon Tracy , Jackson Brian P. , Hopp Marie-T. , McDaniel Larry S. , Akerley Brian J. , Imhof Diana , Vidal Jorge E. 
Published: November 2023

SummaryPneumococcal pneumonia causes cytotoxicity in the lung parenchyma but the underlying mechanism involves multiple factors contributing to cell death. Here, we discovered that hydrogen peroxide produced byStreptococcus pneumoniae(Spn-H2O2) plays a pivotal role by oxidizing hemoglobin, leading to its polymerization and subsequent release of labile heme. At physiologically relevant levels, heme selected a population of encapsulated pneumococci. In the absence of capsule and Spn-H2O2, host intracellular heme exhibited toxicity towards pneumococci, thus acting as an antibacterial mechanism. Further investigation revealed that heme-mediated toxicity required the ABC transporter GlnPQ.In vivoexperiments demonstrated that pneumococci release H2O2to cause cytotoxicity in bronchi and alveoli through the non-proteolytic degradation of intracellular proteins such as actin, tubulin and GAPDH. Overall, our findings uncover a mechanism of lung toxicity mediated by oxidative stress that favor the growth of encapsulated pneumococci suggesting a therapeutic potential by targeting oxidative reactions.Graphical abstractHighlightsOxidation of hemoglobin byStreptococcus pneumoniaefacilitates differentiation to encapsulated pneumococciin vivoDifferentiatedS. pneumoniaeproduces capsule and hydrogen peroxide (Spn-H2O2) as defense mechanism against host heme-mediated toxicity.Spn-H2O2-induced lung toxicity causes the oxidation and non-proteolytic degradation of intracellular proteins tubulin, actin, and GAPDH.The ABC transporter GlnPQ is a heme-binding complex that makes Spn susceptible to heme toxicity.
Epigenetics and chromatin structure regulatevar2csaexpression and the placental binding phenotype inPlasmodium falciparum
Authors: Lenz Todd , Sirel Madle , Hoppe Hannes , Shafeeq Sulman , Roch Karine Le , Ribacke Ulf 
Published: November 2023

ABSTRACTPlasmodium falciparumis responsible for what appears to be a never-ending public health issue in the developing world. With repeated infections, a gradual semi-immunity to severe malaria can be acquired but this is disrupted when women become pregnant as the parasite cytoadheres in the placenta to prevent splenic clearance. This change in tissue tropism is due to specific expression of the antigenically variable adhesin VAR2CSA. To better understand the molecular mechanisms activatingvar2csaand antigenic variation over all, we used a combination of phenotypic and systems biology assays. We first established phenotypically homogenous populations of VAR2CSA expressing and placenta binding parasites that were shown to exclusively transcribevar2csawhile all othervargenes remained silenced. We also confirmed that the transcriptional activation was strongly associated with distinct depletion of repressive H3K9me3 marks. Further, we used chromatin conformation capture as a high-resolution approach to determine interchromosomal interactions and established that transcriptional activation is linked to a small yet significant repositioning ofvar2csarelative to heterochromatic telomeric clusters. Lastly, we demonstrated that occupancy of 5-methylcytosine was present in allvargenes but independent of transcriptional activation and switching. All together, these findings provide insights at high resolution into the potential role of 5-methylcytosine inP. falciparumand increase our understanding of the mechanisms regulating antigenic variation at the epigenetics and chromatin structure level.
Cryptography in the DNA of living cells enabled by multi-site base editing
Authors: Volf Verena , Zhang Simon , Song Karen M. , Qian Sharon , Chen Fei , Church George M. 
Published: November 2023

AbstractAlthough DNA is increasingly being adopted as a generalizable medium for information storage and transfer, reliable methods for ensuring information security remain to be addressed. In this study, we developed and validated a cryptographic encoding scheme, Genomic Sequence Encryption (GSE), to address the challenge of information confidentiality and integrity in biological substrates. GSE enables genomic information encoding that is readable only with a cryptographic key. We show that GSE can be used for cell signatures that enable the recipient of a cell line to authenticate its origin and validate if the cell line has been modified in the interim. We implement GSE through multi-site base editing and encode information through editing across >100 genomic sites in mammalian cells. We further present an enrichment step to obtain individual stem cells with more than two dozen edits across a single genome with minimal screening. This capability can be used to introduce encrypted signatures in living animals. As an encryption scheme, GSE is falsification-proof and enables secure information transfer in biological substrates.
Heparan sulfate dependent phase separation of CCL5 and its chemotactic activity
Authors: Yu Xiaolin , Duan Guangfei , Pei Pengfei , Chen Long , Gu Renji , Hu Wenrui , Zhang Hongli , Wang Yan-Dong , Gong Lili , Liu Lihong , Chu Ting-Ting , Li Jin-Ping , Luo Shi-Zhong 
Published: November 2023

AbstractSecreted chemokines form concentration gradients in target tissues to control migratory directions and patterns of immune cells in response to inflammatory stimulation; however, how the gradients are formed is much debated. Heparan sulfate (HS) binds to chemokines and modulates their activities. In this study, we investigated the roles of HS in the gradient formation and chemoattractant activity of CCL5 that is known to bind to HS. CCL5 and heparin underwent liquid–liquid phase separation (LLPS) and formed gradient, which was confirmed using CCL5 immobilized on heparin-beads. The biological implication of HS in CCL5 gradient formation was established in CHO-K1 (wild type) and CHO-677 (lacking HS) cells by Transwell assay. The effect of HS on CCL5 chemoattractant activity was further proved by Transwell assay of human peripheral blood cells. Finally, peritoneal injection of the chemokines into mice showed reduced recruitment of inflammatory cells either by mutant CCL5 (lacking heparin binding sequence) or by addition of heparin to wild type CCL5. Our experimental data propose that co-phase separation of CCL5 with HS establishes a specific chemokine concentration gradient to trigger directional cell migration. The results warrant further investigation on other heparin binding chemokines and allows for a more elaborate insight into disease process and new treatment strategies.
Single-cell morphological tracking of liver cell states to identify small-molecule modulators of liver differentiation
Authors: Graham Rebecca E. , Zheng Runshi , Wagner Jesko , Unciti-Broceta Asier , Hay David C. , Forbes Stuart J. , Gadd Victoria L. , Carragher Neil O. 
Published: November 2023

AbstractAlternative therapeutic strategies are urgently required to treat liver disease, which is responsible for 2 million deaths anually. By combining Cell Painting, a morphological profiling assay that captures diverse cellular states, with the bi-potent HepaRG®liver progenitor cell line, we have developed a high-throughput, single-cell technique, to track liver cell fate and map small-molecule induced changes using a morphological atlas of bi-lineage liver cell differentiation. To our knowledge this is the first-time single-cell trajectory inference has been applied to image-based Cell Painting data and leveraged for drug screening. The overarching goal of this new method is to aid research into understanding liver cell regeneration mechanisms and facilitate the development of cell-based and small-molecule therapies. Using this approach, we have identified a class of small-molecule SRC family kinase inhibitors that promote differentiation of HepaRG®single-cells towards the hepatocyte-like lineage and promotes differentiation of primary human hepatic progenitor cells towards a hepatocyte-like phenotypein vitro.
Omecamtiv mecarbil and Mavacamten target the same myosin pocket despite antagonistic effects in heart contraction
Authors: Auguin Daniel , Robert-Paganin Julien , Réty Stéphane , Kikuti Carlos , David Amandine , Theumer Gabriele , Schmidt Arndt W. , Knölker Hans-Joachim , Houdusse Anne 
Published: November 2023

SummaryInherited cardiomyopathies are amongst the most common cardiac diseases worldwide, leading in the late-stage to heart failure and death. The most promising treatments against these diseases are small-molecules directly modulating the force produced by β-cardiac myosin, the molecular motor driving heart contraction. Two of these molecules that produce antagonistic effects on cardiac contractility have completed clinical phase 3 trials: the activatorOmecamtiv mecarbiland the inhibitorMavacamten. In this work, we reveal by X-ray crystallography that both drugs target the same pocket and stabilize a pre-stroke structural state, with only few local differences. All atoms molecular dynamics simulations reveal how these molecules can have antagonistic impact on the allostery of the motor by comparing β-cardiac myosin in the apo form or bound toOmecamtiv mecarbilorMavacamten. Altogether, our results provide the framework for rational drug development for the purpose of personalized medicine.
Arterial mechanics, extracellular matrix, and smooth muscle differentiation in carotid arteries deficient for Rac1
Authors: Assoian Richard K. , Xu Tina , Roberts Emilia 
Published: November 2023

SummaryStiffening of the extracellular matrix (ECM) occurs after vascular injury and contributes to the injury-associated proliferation of vascular smooth muscle cells (SMCs). ECM stiffness also activates Rac-GTP, and SMC Rac1 deletion strongly reduces the proliferative response to injuryin vivo. However, ECM stiffening and Rac can affect SMC differentiation, which, in itself, can influence ECM stiffness and proliferation. Here, we used pressure myography and immunofluorescence analysis of mouse carotid arteries to ask if the reported effect of Rac1 deletion onin vivoSMC proliferation might be secondary to a Rac effect on basal arterial stiffness or SMC differentiation. The results show that Rac1 deletion does not affect the abundance of arterial collagen-I, -III, or -V, the integrity of arterial elastin, or the arterial responses to pressure, including the axial and circumferential stretch-strain relationships that are assessments of arterial stiffness. Medial abundance of alpha-smooth muscle actin and smooth muscle-myosin heavy chain, markers of the SMC differentiated phenotype, were not statistically different in carotid arteries containing or deficient in Rac1. Nor did Rac1 deficiency have a statistically significant effect on carotid artery contraction to KCl. Overall, these data argue that the inhibitory effect of Rac1 deletion onin vivoSMC proliferation reflects a primary effect of Rac1 signaling to the cell cycle rather than a secondary effect associated with altered SMC differentiation or arterial stiffness.
Exploring the effects of virtual annotation background display mode and transparency through a 360-degree panorama approach to online shopping
Authors: Zhai Weimin , Lin Zhongzhen , Xu Biwen 
Published: November 2023

PurposeWith the rapid development of technology, 360° panorama on mobile as a very convenient way to present virtual reality has brought a new shopping experience to consumers. Usually, consumers get product information through virtual annotations in 360° panorama and then make a series of shopping behaviors. The visual design of virtual annotation significantly influences users' online visual search for product information. This study aims to investigate the influence of the visual design of virtual annotation on consumers' shopping experience in the online shopping interface of 360° panorama.Design/methodology/approachA 2 × 3 between-subject design was planned to help explore whether different display model of annotation (i.e. negative polarity and positive polarity) and different background transparency of annotation (i.e. 0% transparency, 25% transparency and 50% transparency) may affect users' task performance and their subjective evaluations.Findings(1) Virtual annotations with different background transparency affect user performance, and transparency has better visual search performance. (2) Virtual annotation background display mode may affect the user operation performance; the positive polarity of the virtual annotation is more convenient for the users' visual searching for product information. (3) When the annotation background transparency is opaque or semi-transparent, the negative polarity display is more favorable to the users' visual search. However, this situation is reversed when the annotation background transparency is 25%. (4) Participants preferred the presentation of positive polarity virtual annotations. (5) Regarding the degree of willingness to use and ease of understanding, participants preferred the negative polarity display for 0% background transparency or 50% background transparency. However, the opposite result was obtained for 25% background transparency.Originality/valueThe findings generated from the research can be a good reference for the development of virtual annotation visual design for mobile shopping applications.HighlightsVirtual annotation background transparency and background display mode are two essential attributes of 360° panoramas.This study examined how virtual annotation background transparency and background display mode influence user performance and experience.It is recommended to use a translucent or opaque annotation background with a negative polarity display.Virtual annotation presentation with 25% background transparency facilitates consumer searching and comparison of product information.Users prefer a positive polarity annotation display.
Health literacy and subjective well-being amongst university students: moderating role of gender
Authors: Rashid Irfana , Amin Faseeh , Lone Aashiq Hussain , Gulzar Shahzada Shahid 
Published: November 2023

PurposeThe present study has attempted to examine the connection between health literacy (HL) and subjective well-being (SWB) amongst university students in North India. In addition, the present research also sought to establish the role of “gender” and “absence/presence of health professional in the family” as a socio-demographic variable in the relationship between HL and SWB.Design/methodology/approachThis study used a descriptive and quantitative research design. Students were asked to respond to an online questionnaire as part of a survey strategy. Out of 550 respondents who completed the survey, only 511 responses were usable after data cleaning.FindingsThe structural equation modelling regression analysis revealed a positive association between HL and SWB. In addition, the moderating role of gender and the “presence/absence of health professionals in the family” between HL and SWB was also established.Research limitations/implicationsAlthough a sizable sample of university students responded to this poll, it was a convenience sample. The study cannot be generalised to the general population; thus, future scholars can include other socio-demographic sections. Theoretically, it has tested a research framework concerning multiple dimensions of students' SWB and HL. In addition, the moderating role of gender and the “presence/absence of health professionals in the family” is another unique research contribution of this study.Practical implicationsThe results of the current study provided evidence that HL promotion efforts are needed amongst the student population in India to enhance their well-being. The objective of practitioners and relevant stakeholders (parents, government agencies and universities) should be to build capacities concerning HL at both personal and institutional levels. Based on the findings, more educational programmes should be created for the students to promote HL and raise awareness of healthy lifestyles.Originality/valueThe degree to which people can locate, comprehend and use information and services to support health-related decisions and actions for themselves and others is known as “health literacy.” HL is closely associated with SWB, which means how people perceive and assess their lives and particular spheres and activities within them. The current research on the relationship between the two domains is limited. This study looked into the effects of HL on SWB amongst university students in North India.