bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intervening to preserve function in ischemic cardiomyopathy with a porous hydrogel and extracellular matrix composite in a rat myocardial infarction model
Authors: Hayashi Yasunari , Fujii Taro , Kim Seungil , Badylak Stephen F. , D’Amore Antonio , Wagner William R. 
Published: July 2024

AbstractA variety of hydrogels have been developed for intramyocardial injection therapy after myocardial infarction. Some of these biomaterials have incorporated bioactive substances that promote local tissue regeneration and integration, while others have emphasized the mechanical role of the injectate in providing functional benefit. In this study, we incorporated two bioactive features, porosity, and extracellular matrix derived hydrogel (ECM), into a mechanically optimized, thermoresponsive, degradable hydrogel (poly(N-isopropylacrylamide-co-N-vinylpyrrolidone-co-MAPLA) copolymer) and evaluated whether injection of this biomaterial could abrogate the remodeling process in a rat ischemic cardiomyopathy model. After myocardial infarction by coronary artery ligation, rats were randomly divided into four groups: group NP (non-porous hydrogel) without either ECM or porosity, group PM (porous hydrogel) from the same synthetic copolymer with mannitol beads as porogens, and group PME with porosity and ECM digest added to the synthetic copolymer. A group with PBS injection alone served as a control. Intramyocardial injections were made 3 days after myocardial infarction. Serial echocardiography was assessed over time, and histological assessments were performed eight weeks after infarction. Results demonstrated improved echocardiographic function and neovascularization in the PME group compared to the other hydrogels and PBS injection. The PME group also demonstrated significant improvement in LV geometry and macrophage polarization (towards M2) compared to the PBS group, whereas these differences were not observed in the NP or PM groups versus the control. These results demonstrate that further functional improvement may be achieved in hydrogel injection therapy for ischemic cardiomyopathy by incorporating porosity and ECM digest, representing a combination of mechanical and biological effects.
Exenatide administration time determines the effects on blood pressure dipping indb/dbmice via modulation of food intake and sympathetic activity
Authors: Chacon Aaron N. , Su Wen , Hou Tianfei , Guo Zhenheng , Gong Ming C. 
Published: July 2024

AbstractType 2 diabetics have an increased prevalence of hypertension and nondipping blood pressure (BP), which worsen cardiovascular outcomes. Exenatide, a short acting glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat type 2 diabetes, also demonstrates blood pressure (BP)-lowering effects. However, the mechanisms behind this and the impact of administration timing on BP dipping remain unclear. We investigated the effects of exenatide intraperitoneal injected at light onset (ZT0) or dark onset (ZT12) in diabetic (db/db) mice and nondiabetic controls. Using radio-telemetry and BioDAQ cages, we continuously monitored BP and food intake. Db/db mice exhibited non-dipping BP and increased food intake. ZT0 exenatide administration restored BP dipping by specifically lowering light-phase BP, while ZT12 exenatide reversed dipping by lowering dark-phase BP. These effects correlated with altered food intake patterns, and importantly, were abolished when food access was removed. Additionally, urinary norepinephrine excretion, measured by HPLC, was significantly reduced 6 hours post-exenatide at both ZT0 and ZT12, suggesting sympathetic nervous system involvement. Notably, combining exenatide with either ganglionic blocker mecamylamine or α-blocker prazosin did not enhance BP reduction beyond the individual effects of each blocker. These findings reveal that exenatide, when administered at light onset, restores BP dipping in db/db mice by suppressing light-phase food intake and sympathetic activity. Importantly, the efficacy of exenatide is dependent on food availability and its timing relative to circadian rhythms, highlighting the potential for chronotherapy in optimizing GLP-1RA- based treatments for type 2 diabetes and hypertension.Graphic AbstractArticle HighlightsMaintaining a normal blood pressure (BP) circadian rhythm is vital for cardiovascular health, but diabetes often disrupts this rhythm. The effect of exenatide, a GLP-1 receptor agonist (GLP-1RA), on BP rhythm in diabetes is uncertain.This study investigates the impact of exenatide administration timing on BP patterns in diabetic db/db mice.Findings indicate that exenatide given at the onset of rest restores normal BP dipping, while at the start of the active phase worsens BP rhythm by modulating food intake and sympathetic activity.Timing GLP-1 RA administration may optimize BP control and provide cardiovascular benefits for type 2 diabetes patients.
Tks5 interactome reveals ER-associated machinery translation in invadosomes
Authors: Normand Léa , Bonnard Benjamin , Sala Margaux , Di-Tommaso Sylvaine , Dourthe Cyril , Raymond Anne-Aurélie , Dupuy Jean-William , Mercier Luc , Goetz Jacky G. , Moreau Violaine , Henriet Elodie , Saltel Frédéric 
Published: July 2024

AbstractThe ability to progress and invade through the extracellular matrix is a characteristic shared by both normal and cancer cells through the formation of structures called invadosomes gathering invadopodia and podosomes. These invadosomes are plastic and dynamic structures that can adopt different organizations depending on the cell types and the environment such as rosettes, dots or linear invadosomes. In this study, we used the specific invadosome marker Tks5 (SH3PXD2A), to identify common features in these different organizations. Tks5 immunoprecipitation coupled with mass spectrometry analysis allowed us to identify common proteins in these different models. We identified elements of the translation machinery, in particular the EIF4B protein, but also endoplasmic reticulum (ER) proteins as part of the invadosome structure. Providing new data on invadosome molecular composition through Tks5 interactome, we identified that ER-associated translation machinery is recruited to invadosome and involved in their formation, persistence and function in all types of invadosomes.SummaryInvadosomes are invasive F-actin structures exhibiting different organizations that degrade the extracellular matrix. The study uses their universal marker, Tks5, to provide new data about invadosome molecular composition and reveal the role of ER-associated translation machinery in invadosome formation and function.
3D directional tuning in the orofacial sensorimotor cortex during natural feeding and drinking
Authors: Hosack Victoria B. , Arce-McShane Fritzie I. 
Published: July 2024

AbstractDirectional tongue movements are essential for vital behaviors, such as feeding and speech, to position food for chewing and swallowing safely and to position the tongue for accurate sound production. While directional tuning has been well-studied in the arm region of the sensorimotor cortex during reaching tasks, little is known about how 3D tongue direction is encoded in the orofacial region during natural behaviors. Understanding how tongue direction is represented in the brain has important implications for improving rehabilitation for people with orolingual dysfunctions. The goal of this study is to investigate how 3D direction of tongue movement is encoded in the orofacial sensorimotor cortex (OSMCx) during feeding and drinking, and how this process is affected by the loss of oral sensation. Using biplanar video-radiography to track implanted markers in the tongue of behaving non-human primates (Macaca mulatta), 3D positional data was recorded simultaneously with spiking activity in primary motor (MIo) and somatosensory (SIo) areas of the orofacial cortex using chronically implanted microelectrode arrays. In some sessions, tasks were preceded by bilateral nerve block injections to the sensory branches of the trigeminal nerve. Modulation to the 3D tongue direction was found in a majority of MIo but not SIo neurons during feeding, while the majority of neurons in both areas were modulated to the direction of tongue protrusion during drinking. Following sensory loss, the proportion of directionally tuned neurons decreased and shifts in the distribution of preferred direction were observed in OSMCx neurons. Overall, we show that 3D directional tuning of MIo and SIo to tongue movements varies with behavioral tasks and availability of sensory information.
Multi-dimensional demarcation of phylogenetic groups of plant 14-3-3 isoforms using biochemical signatures
Authors: Sedlov Ilya A. , Sluchanko Nikolai N. 
Published: July 2024

AbstractInteraction of dimeric 14-3-3 proteins with numerous phosphotargets regulates various physiological processes in plants, from flowering to transpiration and salt tolerance. Several genes express distinct 14-3-3 ‘isoforms’, particularly numerous in plants, but comparative studies of all 14-3-3 isoforms for a given organism have not been undertaken. Here we systematically investigated twelve 14-3-3 isoforms from the model plantArabidopsis thaliana, uniformly capable of homodimerization at high protein concentration. We unexpectedly discovered that, at physiological protein concentrations, four isoforms representing a seemingly more ancestral, epsilon phylogenetic group (iota, mu, omicron, epsilon) demonstrate an outstanding monomerization propensity and enhanced surface hydrophobicity, which is uncharacteristic for eight non-epsilon isoforms (omega, phi, chi, psi, upsilon, nu, kappa, lambda). Further analysis revealed that dramatically lowered thermodynamic stabilities entail aggregation of the epsilon-group isoforms at near-physiological temperatures and provoke their proteolytic degradation. Structure-inspired single mutations in 14-3-3 iota could rescue non-epsilon behavior, thereby pinpointing key positions responsible for the phylogenetic demarcation. Combining two major demarcating positions (namely, 27th and 51st in omega) and multi-dimensional differences in biochemical properties identified here, we developed a predictor strongly supporting categorization of abundant 14-3-3 isoforms widely across plant groups, from Eudicots to Monocots, Gymnosperms and Lycophytes. In particular, our approach fully recapitulates the phylogenetic epsilon/non-epsilon demarcation in Eudicots and supports the presence of isoforms of both types in more primitive plant groups such asSelaginella, thereby refining solely sequence-based analysis in evolutionarily distant species and providing novel insights into the evolutionary history of the epsilon phylogenetic group.SignificanceDespite over 30 years of research, systematic comparative studies on the regulatory plant 14-3-3 proteins have not been undertaken, making phylogenetic classification of numerous plant 14-3-3 isoforms in different species unreliable. Working on twelve purifiedArabidopsis14-3-3 isoforms, we have discovered a set of biochemical signatures that can be used to robustly and widely categorize epsilon and non-epsilon plant 14-3-3 isoforms, also identifying at least two amino acid positions responsible for such multi-dimensional demarcation.
Thalamic Influence Over Adaptive Cortical Dynamics Across Conscious States
Authors: Müller Eli J. , Munn Brandon R. , Baracchini Giulia , Fulcher Ben D. , Medel Vicente , Redinbaugh Michelle J. , Saalmann Yuri B. , Brunton Bingni W. , Brunton Steven L. , Shine James M. 
Published: July 2024

SummaryThe human brain must support both stable and flexible neural dynamics in order to adapt to changing contexts that are inherently non-linear. The thalamus has been linked to the coordination of these opposing dynamical regimens in the cerebral cortex, however existing methodological approaches have not integrated sufficient neurobiological details with a sensitive measure of neural dynamics that permits sensitivity to time-series non-linearities. Inspired by the field of fluid dynamics, we use a novel approach to show that spontaneous fMRI data exhibits non-trivial fluctuations in predictability over time, akin to a river that has sections of smooth and predictable (laminar) versus rough and unpredictable (non-laminar) fluid flow. We use a combination of pharmacological fMRI, macaque electrophysiology and a large-scale biophysical model of the thalamocortical system to provide robust evidence that the thalamus provides versatile control over globally linear dynamics in the cerebral cortex that characterize conscious states.
SID-2 localises to extracellular vesicles in parasitic nematodes and does not function in environmental RNAi
Authors: Blow Frances , Jeffrey Kate , Chow Franklin Wang-Ngai , Nikonorova Inna A. , Barr Maureen M. , Cook Atlanta G. , Prevo Bram , Cheerambathur Dhanya K. , Buck Amy H. 
Published: July 2024

ABSTRACTIn the free-living nematodeCaenorhabditis elegansthe transmembrane protein SID-2 imports double-stranded RNA into intestinal cells to trigger systemic RNA interference (RNAi), allowing organisms to sense and respond to environmental cues such as the presence of pathogens. This process, known as environmental RNAi, has not been observed in the most closely related parasites that are also within clade V. Previous sequence-based searches failed to identifysid-2orthologs in available clade V parasite genomes. In this study we identifiedsid-2orthologues in these parasites using genome synteny and protein structure-based comparison, following identification of a SID-2 orthologue in extracellular vesicles from the murine intestinal parasitic nematodeHeligmosomoides bakeri. Expression of GFP-taggedH. bakeriSID-2 inC. elegansshowed comparable localisation to the intestinal apical membrane as seen for GFP-taggedC. elegansSID-2 and further showed mobility in intestinal cells in vesicle-like structures. We tested the capacity ofH. bakeriSID-2 to functionally complement environmental RNAi in aC. elegansSID-2 null mutant and show thatH. bakeriSID-2 does not rescue the phenotype in this context. Therefore, our work identifies SID-2 as a highly abundant nematode EV protein whose ancestral function may be unrelated to environmental RNA and rather highlights an association with extracellular vesicle-mediated communication in free-living and parasitic nematodes.
Heat pre-treatment reduces multiplicity of plasmid transformations in yeast during electroporation, without diminishing the transformation efficiency
Authors: Wäneskog Marcus , Hoch-Schneider Emma Elise , Garg Shilpa , Kronborg Cantalapiedra Christian , Schaefer Elena , Krogh Jensen Michael , Damgaard Jensen Emil 
Published: July 2024

AbstractHigh-throughput DNA transformation techniques are invaluable when creating high-diversity mutant libraries, and the success rate of any protein engineering endeavors is directly dependent on both the size and diversity of the mutant library that is to be screened. It is also widely accepted that in both bacteria and yeast there is an inverse correlation between the DNA transformation efficiency and the likelihood of transforming multiple DNA molecules into each cell. However, most successful high-throughput mutant screening efforts require high quality libraries, i.e., libraries comprised of cells with a clear phenotype-to-genotype relationship (one genotype/cell). Thus, DNA transformation methods with a high multiplicity of transformation are highly undesirable and detrimental to most mutant screening assays. Here we describe a simple, robust, and highly efficient yeast plasmid DNA transformation methodology, using a dual heat-shock and electroporation approach (HEEL) that generates more than 2 x 107plasmid-transformed yeast cells per reaction, while simultaneously increasing the fraction of mono-transformed cells from 20% to more than 70% of the transformed population. By also using an automated yeast genotyping workflow coupled with a dual-barcoding approach, consisting of a SNP and high-diversity barcode (10N), we can consistently identify and enumerate unique plasmid genotypes within a heterogeneous population merely through Sanger sequencing. We demonstrate here that the size and quality of a transformed library no longer need to be inversely correlated when transforming large mutant DNA libraries in yeast using highly efficient DNA electroporation methods.SignificanceWith the recent expansion of artificial intelligence in the field of synthetic biology there has never been a greater need for high-quality data and reliable measurements of phenotype-to-genotype relationships. However, one major obstacle to creating accurate computer-based models is the current abundance of low-quality phenotypic measurements originating from numerous high-throughput, but low-resolution assays. Rather than increasing the quantity of measurements, new studies should aim to generate as accurate measurements as possible. The HEEL methodology presented here aims to address this issue by minimizing the problem of multi-plasmid uptake during high-throughput yeast DNA transformations, which leads to the creation of heterogeneous cellular genotypes. HEEL should enable highly accurate phenotype-to-genotype measurements going forward, which could be used to construct better computer-based models.
Characterizing Excretory-Secretory Products Proteome Across Larval Development Stages inAscaris suum
Authors: Castañeda Sergio , Adeniyi-Ipadeola Grace , Wu Yifan , Suarez-Reyes Charlie , Jain Antrix , Ramírez Juan David , Weatherhead Jill E. 
Published: July 2024

AbstractIntroductionAscaris lumbricoidesandAscaris suumare parasitic nematodes that primarily infest the small intestines of humans and pigs, respectively. Ascariasis poses a significant threat to human health and swine health. UnderstandingAscarislarval development is crucial for developing novel therapeutic interventions that will prevent ascariasis in both humans and pigs. This study aimed to characterize the excretory-secretory (ES) proteome of differentAscaris suumlarval stages (L3-egg, L3-lung, L3-trachea) to identify potential targets for intervention to preventAscaris-induced global morbidity.MethodsStage-specific larvae were isolated, cultured in vitro and ES-product was collected. Third-stageAscarislarvae (L3) were isolated from embryonated eggs (L3-egg), isolated from the lungs of Balb/c mice infected withAscaris suumeggs at day 8 post infection (L3-lungs) and isolated from the trachea of Balb/c mice infected withAscaris suumeggs at day 12 post infection (L3-trachea). ES products were obtained by culturing larvae. Proteomic analysis was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatic tools including MaxQuant, Perseus, and Andromeda, following a detailed protocol available on GitHub. The analysis encompassed peptide identification, scoring, and quantification against an organism-specific database, with subsequent quality control, correlation assessment, and differential abundance determination using the Amica algorithm.ResultsA total of 58 unique proteins were identified in the ES products. Fourteen proteins were common across all stages, while others were stage-specific. Principal component analysis revealed distinct protein profiles for each stage, suggesting qualitatively different proteomes. Gene ontology analysis indicated stage-specific GO enrichment of specific protein classes, such as nuclear proteins in L3-egg ES products and metabolic enzymes in L3-lung and L3-trachea ES products.DiscussionThis study revealed stage-specific differences in the composition ofAscarisES products. Further investigation into the functional roles of these proteins and their interactions with host cells is crucial for developing novel therapeutic and diagnostic strategies against ascariasis.
NPM1 mediates genome-nucleolus interactions and the establishment of their repressive chromatin states
Authors: Gupta Shivani , Bersaglieri Cristiana , Bär Dominik , Raingeval Mathieu , Schaab Luana , Santoro Raffaella 
Published: July 2024

AbstractRepressive chromatin domains are often located at the nuclear lamina (NL) or nucleolus. Although nucleolar associated domains (NADs) have been recently mapped, the mechanisms of NAD association with nucleoli and the functional significance of their localization remain unclear. Here, we show that NAD association with nucleoli is mediated by nucleophosmin (NPM1), a factor located within the granular component, the outer layer of the nucleolus. NPM1 binds NADs, interacts with the histone lysine methyltransferase G9a (EHMT2), and is required for establishing H3K9me2 at NADs. Loss of NPM1 or expression of NPM1 mutant lacking the DNA binding domain (NPM1ΔDBD) caused NAD dissociation from nucleoli and H3K9me2 reduction specifically at NADs. G9a is dispensable for NAD contacts with nucleoli and interacts with NPM1ΔDBD, indicating that NADs acquire G9a-mediated H3K9me2 only after associating with NPM1 at nucleoli. The results provide mechanistic insights into how genomic domains associate with nucleoli and acquire their repressive chromatin state. Additionally, our findings suggest that the nucleolus not only serves as a scaffold for positioning repressive chromatin domains but also plays a direct role in establishing these chromatin states.
Medical tourism in South East Asia: science mapping of present and future trends
Authors: Fauzi Muhammad Ashraf , Mohd Aripin Norhana , Alimin Nur Sofia Nabila , Ting Irene Wei Kiong , Wider Walton , Maidin Siti Sarah , Zainul Abideen Ahmed 
Published: July 2024

PurposeThis study evaluates the knowledge structure of medical tourism within the geographical context of South East Asia. This region is one of the growing economic powerhouses in the world, and tourism activities have contributed a lot to its advancement.Design/methodology/approachApplying a science mapping technique using bibliometric analysis, the current and emerging themes and future trends are analyzed using bibliographic coupling and co-word analysis.FindingsFindings show that current trends produced four themes: Fundamentals of medical tourism in Southeast Asia, determinants of tourist medical tourism visits, quality of medical and health service in Southeast Asia and impact of medical tourism on national economic growth. The future trends also produced four themes related to navigating excellence in medical tourism, medical tourism and economic growth, service quality in medical tourism services and accredited destinations in the globalized era of medical tourism.Research limitations/implicationsThis study is relevant to all stakeholders, operators and local communities in Southeast Asia tourism destinations to provide the best medical tourism with the best quality service and technologies.Originality/valueThis study fills the gap by performing a bibliometric approach to reviewing medical tourism in Southeast Asia using a science mapping technique. Crucial themes are produced through topological and temporal streams that provide critical insight for future developments in medical tourism in the region.