bluuebunny/crossref_metadata_2025_split huggingface dataset:
17 β-estradiol impedes aortic root dilation and rupture in male Marfan mice
Authors: Saddic Louis , Escopete Sean , Zilberberg Lior , Kalsow Shannon , Gupta Divya , Egbhali Mansoureh , Parker Sarah 
Published: May 2023

AbstractMarfan syndrome causes a hereditary form of thoracic aortic aneurysms with dilation of the aortic root. Human and animal models suggest a worse phenotype for males compared to females with respect to aneurysm size and risk of dissection. In this study we examine the effects of 17 β-estradiol on aortic dilation and rupture in a Marfan mouse model. Marfan male mice were administered 17 β-estradiol and the growth in aortic root size along with the risk of aortic rupture or dissection with the addition of angiotensin II was measured. Transcriptomic profiling was used to identify enriched pathways from 17 β-estradiol treatment. Aortic smooth muscle cells were then treated with cytokines in order to validate the mechanism of 17 β-estradiol protection. We show that 17 β-estradiol decreased the size and rate of aortic root dilation and improved survival from rupture and dissection after treatment with angiotensin II. The Marfan transcriptome was enriched in inflammatory genes and the addition of 17 β-estradiol modulated a set of genes that function through TNFα mediated NF-κB signaling. These included many proteins known to play a role in the phenotypic shift of aortic smooth muscle cells from a contractile to a more inflammatory-like state such as Vcam-1, Mcp-1, Lgals3, Il-6, Il-1b, and C3. In addition, 17 β-estradiol suppressed the induction of these TNFα induced genes in aortic smooth muscle cells in vitro and this effect appears to be NF-κB dependent. In conclusion, 17 β-estradiol protects against the dilation and rupture of aortic roots in Marfan male mice through the inhibition of TNFα -NF-κB signaling and thus prevents the phenotypic switch of aortic smooth muscle cells from a contractile to an inflammatory state.
E2F1 promotes, JNK and DIAP1 inhibit, and chromosomal position has little effect on radiation-induced Loss of Heterozygosity inDrosophila
Authors: Brown Jeremy , Su Tin Tin 
Published: May 2023

AbstractLoss of Heterozygosity (LOH) can occur when a heterozygous mutant cell loses the remaining wild type allele to become a homozygous mutant. LOH can have physiological consequences if, for example, the affected gene encodes a tumor suppressor. We used two fluorescent reporters to study mechanisms of LOH induction by X-rays, a type of ionizing radiation (IR), inDrosophilalarval wing discs. IR is used to treat more than half of cancer patients, so understanding its effects is of biomedical relevance. Quantitative analysis of IR-induced LOH at seven different positions between the telomere and the centromere, the first such study that we know of, showed that while a homologous chromosome is required to produce LOH after irradiation, position along the chromosome makes little difference. This suggests that IR-induced LOH occurs via non-recombination-based mechanisms, unlike what was previously reported for spontaneously occurring LOH. Using a focused screen, we identified E2F1 as a key promotor of LOH and further testing suggests a mechanism involving its role in cell cycle regulation rather than apoptosis. We leveraged the loss of a transcriptional repressor through LOH to express transgenes specifically in cells that have already acquired LOH. This approach identified JNK signaling and apoptosis as key determinants of LOH maintenance. These studies reveal previously unknown mechanisms for generation and elimination of cells with chromosome aberrations after exposure to IR.SummaryLoss of Heterozygosity (LOH) can lead to homozygous mutant cells, with potential physiological consequences if it affects tumor suppressor genes. Using fluorescent reporters of LOH inDrosophilawing discs, we found that X-ray-induced LOH requires a homologous chromosome but was unaffected by position along the chromosome. This suggests non-recombination mechanisms for X-ray-induced LOH, unlike spontaneous LOH. We found that E2F1 promotes LOH while JNK signaling and apoptosis eliminates cells with LOH, uncovering new insights into chromosomal aberrations post-exposure to radiation.
Acute resistance exercise-induced changes in IL-6, IL-10, and IL-1ra in healthy adults: a systematic review and meta-analysis
Authors: Ringleb Miriam , Javelle Florian , Haunhorst Simon , Bloch Wilhelm , Fennen Lena , Baumgart Sabine , Drube Sebastian , Reuken Philipp A. , Pletz Mathias W. , Wagner Heiko , Gabriel Holger H. W. , Puta Christian 
Published: May 2023

AbstractBackgroundMyokines, released from the contracting muscle, enable communication between the working muscles and other tissue. Their release during physical exercise is assumed to depend on mode, duration, and intensity.ObjectiveThe aim of this meta-analysis is to examine the acute changes in circulating levels of the myokines IL-6, IL-10, and IL-1ra induced by a bout of resistance exercise and to consider potential moderators of the results.MethodsSystematic literature search was conducted for resistance exercise intervention studies measuring IL-6, IL-10, or IL-1ra before and immediately after resistance exercise in healthy individuals. Random effects meta-analysis was performed for each myokine.ResultsA small to moderate positive effect of resistance exercise for IL-6 and a moderate to large positive effect for IL-1ra were detected. For IL-10 no significant effect was observed. No moderators (training status, type of exercise, risk of bias, age, exercise volume, exercise intensity, exercise dose) of the results were detected.ConclusionThis systematic review and meta-analysis clearly showed the immediate positive effects of an acute resistance exercise session on IL-6 and IL-1ra levels.
Prognostic Value of Myocardial Perfusion Imaging by Cadmium Zinc Telluride Single-photon Emission Computed Tomography in Patients with Suspected or Known Coronary Artery Disease A Systematic Review and Meta-analysis
Authors: Assante Roberta , Zampella Emilia , Cantoni Valeria , Green Roberta , D’Antonio Adriana , Mannarino Teresa , Gaudieri Valeria , Nappi Carmela , Buongiorno Pietro , Panico Mariarosaria , Petretta Mario , Cuocolo Alberto , Acampa Wanda 
Published: May 2023

AbstractBackgroundAim of this study was to define the prognostic value of stress myocardial perfusion imaging by cadmium zinc telluride (CZT) single-photon emission computed tomography (SPECT) for prediction of adverse cardiovascular events in patients with known or suspected coronary artery disease (CAD).Methods and ResultsStudies published until November 2022 were identified by database search. We included studies using stress myocardial perfusion imaging by CZT-SPECT to evaluate subjects with known or suspected CAD and providing primary data of adverse cardiovascular events. Total of 12 studies were finally included recruiting 36,415 patients. Pooled hazard ratio (HR) for the occurrence of adverse events was 2.17 (95% confidence interval, CI, 1.78-2.65) and heterogeneity was 66.1% (P=0.001). Five studies reported data on adjusted HR for the occurrence of adverse events. Pooled HR was 1.69 (95% CI, 1.44-1.98) and heterogeneity was 44.9% (P=0.123). Seven studies reported data on unadjusted HR for the occurrence of adverse events. Pooled HR was 2.72 (95% CI, 2.00-3.70). Nine studies reported data useful to calculate separately the incidence rate of adverse events in patients with abnormal and normal myocardial perfusion. Pooled incidence rate ratio was 2.38 (95% CI, 1.39-4.06) and heterogeneity was 84.6% (P<0.001). The funnel plot showed no evidence of asymmetry (P=0.517). At meta-regression analysis, we found an association between HR for adverse events and presence of angina symptoms and family history of CAD.ConclusionsStress myocardial perfusion imaging by CZT-SPECT is a valuable noninvasive prognostic indicator for adverse cardiovascular events in patients with known or suspected CAD.
Detection of new pioneer transcription factors as cell-type specific nucleosome binders
Authors: Peng Yunhui , Song Wei , Teif Vladimir B. , Ovcharenko Ivan , Landsman David , Panchenko Anna R. 
Published: May 2023

AbstractWrapping of DNA into nucleosomes restricts accessibility to the DNA and may affect the recognition of binding motifs by transcription factors. A certain class of transcription factors, the pioneer transcription factors, can specifically recognize their DNA binding sites on nucleosomes, may initiate local chromatin opening and facilitate the binding of co-factors in a cell-type-specific manner. For the majority of human pioneer transcription factors, the locations of their binding sites, mechanisms of binding and regulation remain unknown. We have developed a computational method to predict the cell-type-specific ability of transcription factors to bind nucleosomes by integrating ChIP-seq, MNase-seq and DNase-seq data with details of nucleosome structure. We have demonstrated the ability of our approach in discriminating pioneer from canonical transcription factors and predicted new potential pioneer transcription factors in H1, K562, HepG2 and HeLa cell lines. Lastly, we systemically analyzed the interaction modes between various pioneer transcription factors and detected several clusters of distinctive binding sites on nucleosomal DNA.
Exact calculation of the expected SFS in structured populations
Authors: Arredondo Armando , Corujo Josué , Noûs Camille , Boitard Simon , Chikhi Lounès , Mazet Olivier 
Published: May 2023

AbstractThe Site Frequency Spectrum (SFS), summary statistic of the distribution of derived allele frequencies in a sample of DNA sequences, provides information about genetic variation and can be used to make population inferences. The exact calculation of the expected SFS in panmictic population has been derived in the Markovian coalescent theory for decades, but its generalization to the structured coalescent is hampered by the almost exponential growth of the states space. We propose here a complete algorithmic procedure, from how to build a suitable state space and sort it, to how to take advantage of the sparsity of the rate matrix and to solve numerically the linear system by an iterative method. The simplest case of the symmetricaln-island is then processed to arrive at a ready-to-use demographic parameters inference framework.
Genome-wide profiling of DNA repair proteins identifies higher-order coordination in single cells
Authors: de Luca Kim L. , Rullens Pim M. J. , Karpinska Magdalena A. , de Vries Sandra S. , Gacek-Matthews Agnieszka , Pongor Lőrinc S. , Legube Gaëlle , Jachowicz Joanna W. , Marieke Oudelaar A. , Kind Jop 
Published: May 2023

AbstractAccurate repair of DNA damage is critical for maintenance of genomic integrity and cellular viability. Because damage occurs non-uniformly across the genome, single-cell resolution is required for proper interrogation, but sensitive detection has remained challenging. Here, we present a comprehensive analysis of repair protein localization in single cells using DamID and ChIC sequencing techniques. This study reports genome-wide binding profiles in response to DNA double-strand breaks induced by AsiSI, and explores variability in genomic damage locations and associated repair features in the context of spatial genome organization. By unbiasedly detecting repair factor localization, we find that repair proteins often occupy entire topologically associating domains, mimicking variability in chromatin loop anchoring. Moreover, we demonstrate the formation of multi-way chromatin hubs in response to DNA damage. Notably, larger hubs show increased coordination of repair protein binding, suggesting a preference for cooperative repair mechanisms. Together, our work offers new insights into the heterogeneous processes underlying genome stability in single cells.
In silicomechanics of stem cells intramyocardially transplanted with a biomaterial injectate for treatment of myocardial infarction
Authors: Motchon YD , Sack KL , Sirry MS , Nchejane NJ , Abdalrahman T , Nagawa J , Kruger M , Pauwels E , Van Loo D , De Muynck A , Van Hoorebeke L , Davies NH , Franz T 
Published: May 2023

AbstractPurposeBiomaterial and stem cell delivery are promising approaches to treating myocardial infarction. However, the mechanical and biochemical mechanisms underlying the therapeutic benefits require further clarification. This study aimed to assess the deformation of stem cells injected with the biomaterial into the infarcted heart.MethodsA microstructural finite element model of a mid-wall infarcted myocardial region was developed fromex vivomicrocomputed tomography data of a rat heart with left ventricular infarct and intramyocardial biomaterial injectate. Nine cells were numerically seeded in the injectate of the microstructural model. The microstructural and a previously developed biventricular finite element model of the same rat heart were used to quantify the deformation of the cells during a cardiac cycle for a biomaterial elastic modulus (Einj) ranging between 4.1 and 405,900 kPa.ResultsThe transplanted cells’ deformation was largest for Einj= 7.4 kPa, matching that of the cells, and decreased for an increase and decrease in Einj. The cell deformation was more sensitive to Einjchanges for softer (Einj≤ 738 kPa) than stiffer biomaterials.ConclusionsCombining the microstructural and biventricular finite element models enables quantifying micromechanics and signalling of transplanted cells in the heart. The approach offers a broader scope forin silicoinvestigations of biomaterial and cell therapies for myocardial infarction and other cardiac pathologies.
Upregulated pexophagy limits the capacity of selective autophagy
Authors: Germain Kyla , So Raphaella W. L. , Watts Joel C. , Bandsma Robert , Kim Peter K. 
Published: May 2023

AbstractSelective autophagy is an essential mechanism to maintain organelle integrity and cellular homeostasis through the constant recycling of damaged or superfluous components. While distinct selective autophagy pathways mediate the degradation of diverse cellular substrates including organelles and pathogens, whether these distinct pathways can influence one another remains unknown. We address this question here using pexophagy, the autophagic degradation of peroxisomes, as a model. We demonstrate in cells that upregulated pexophagy exhausts selective autophagy and limits the degradation of both mitochondria and protein aggregates. We confirmed this finding in the pexophagy-mediated form of Zellweger Spectrum Disorder, a rare disease characterized by peroxisome dysfunction. Further, we extend the generalizability of limited selective autophagy by determining that increased aggrephagy reduces pexophagy using a model of Huntington’s Disease. Our findings suggest that the degradative capacity of selective autophagy can become limited by an increased substrate load.
Sex differences in plasma, adipose tissue, and central accumulation of cannabinoids, and behavioural effects of oral cannabis consumption in male and female C57BL/6 mice
Authors: Sallam Nada , Peterson Colleen , Baglot Samantha L. , Kohro Yuta , Trang Tuan , Hill Matthew N. , Borgland Stephanie L. 
Published: May 2023

AbstractBackgroundCannabis edibles are an increasingly popular form of cannabis consumption. Oral consumption of cannabis has distinct physiological and behavioural effects than injection or inhalation. An animal model is needed to understand the pharmacokinetics and physiological effects of oral cannabis consumption in rodents as a model for human cannabis edible use.MethodsAdult male and female C57BL/6 mice received a single dose of commercially available cannabis oil (5 mg/kg THC) by oral gavage. At 0.5-, 1-, 2-, 3-, and 6-hours post-exposure, plasma, hippocampus, and adipose tissue was collected for THC, 11-OH-THC, and THC-COOH measures.ResultsWe report delayed time to peak THC and 11-OH-THC concentrations in plasma, brain and adipose tissue, which is consistent with human pharmacokinetics studies. We also found sex differences in the cannabis tetrad: (1) female mice had a delayed hypothermic effect 6 hours post-consumption, which was not present in males; (2) females had stronger catalepsy than males; (3) males were less mobile following cannabis exposure, whereas female mice showed no difference in locomotion but an anxiogenic effect at 3h post exposure; and (4) male mice displayed a longer lasting antinociceptive effect of oral cannabis.ConclusionsOral cannabis consumption is a translationally relevant form of administration that produces similar physiological effects as injection or vaping administration and thus should be considered as a viable approach for examining the physiological effects of cannabis moving forward. Furthermore, given the strong sex differences in metabolism of oral cannabis, these factors should be carefully considered when designing animal studies on the effects of cannabis.Significance statementOral delivery of cannabis oil in mice is a translational model that increases plasma, hippocampal, and adipose cannabinoids. Furthermore, oral cannabis and produces lasting psychoactive effects including sex dependent effects on hypothermia, cataplexy, locomotor activity and nociception.
Synergistic effects of dietary taurine and carbohydrates supplementation on skeleton muscle of juvenile turbotScophthalmus maximus
Authors: Hays Hasi , Zhang Wenbing , Mai Kangsen 
Published: May 2023

AbstractThe present study aims to investigate the effects of dietary taurine and carbohydrate levels on the skeleton muscle growth of turbot. Muscle samples of turbot were collected after 70 days of feeding trial by treatment groups of 0% (C), 0.4% (L1), 1.2% (L2) taurine with 15% dietary carbohydrate level, and 0.4% (H1), 1.2% (H2) taurine with 21% dietary carbohydrate level. Results showed that L2 and H2 treatment has given significantly higher hyperplasia with significantly high muscle fiber frequencies and muscle fiber density than that in the other groups. Hyperplastic muscle fiber generation was significantly stimulated by the high carbohydrate level (21%). Muscle density was not dependent on the level of carbohydrates. Aspartate, Threonine, Serine, Glutamine, Leucine, Phenylalanine, Isoleucine, Lysine, Histidine, and Arginine were significantly high in the H1 group than that in other all groups. H2 treatment was given a significantly higher amount of total collagen content than the other groups by increasing alkaline-soluble, alkaline-insoluble hydroxyproline, and total hydroxyproline levels. Hardness has significantly increased in all the treatment groups than that in the control group. And also, muscle hardness was significantly increased by the dietary carbohydrate levels. Intestine amylase, lipase, and trypsin enzyme activities were significantly increased in all the treatment groups than that in the control. Amylase and lipase activities were significantly highest in the H2 group. Taurine 1.2% with carbohydrates 21% treatment group (H2) was given significantly higher levels of cellular level muscle growth with more collagen in the skeletal muscle of Turbot.
Loss of Skeletal Muscle Pyruvate Dehydrogenase Induces Lactic Acidosis and Adaptive Anaplerotic Compensation via Pyruvate-Alanine Cycling and Glutaminolysis
Authors: Gopal Keshav , Abdualkader Abdualrahman Mohammed , Li Xiaobei , Greenwell Amanda A. , Karwi Qutuba G. , Saed Christina , Uddin Golam M. , Darwesh Ahmed M. , Jamieson K Lockhart , Altamimi Tariq R. , Kim Ryekjang , Eaton Farah , Seubert John M. , Lopaschuk Gary D. , Ussher John R. , Al Batran Rami 
Published: May 2023

SUMMARYPyruvate dehydrogenase (PDH) is the rate-limiting enzyme for glucose oxidation that links glycolysis-derived pyruvate with the TCA cycle. Although skeletal muscle is a significant site for glucose oxidation and is closely linked with metabolic flexibility, the importance of muscle PDH during rest and exercise has yet to be fully elucidated. Here, we demonstrate that mice with muscle-specific deletion of PDH exhibit rapid weight loss and suffer from severe lactic acidosis, ultimately leading to early mortality under low-fat diet provision. Furthermore, loss of muscle PDH induces adaptive anaplerotic compensation by increasing pyruvate-alanine cycling and glutaminolysis. Interestingly, high-fat diet supplementation effectively abolishes the early mortality and rescues the overt metabolic phenotype induced by muscle PDH deficiency. Despite increased reliance on fatty acid oxidation during high-fat diet provision, loss of muscle PDH worsens exercise performance and induces lactic acidosis. These observations illustrate the importance of muscle PDH in maintaining metabolic flexibility and preventing the development of metabolic disorders.HighlightsSkeletal Muscle PDH is essential for survivalLoss of muscle PDH induces lactic acidosis and premature deathLoss of muscle PDH enhances pyruvate transformations and glutaminolysisHigh-fat diet supplementation abolishes early mortality and overt phenotype induced by muscle PDH loss
A pair of RNA binding proteins inhibit ion transporter expression to maintain lifespan
Authors: Napier-Jameson Rebekah , Marx Olivia , Norris Adam 
Published: May 2023

ABSTRACTRegulation of lifespan by transcription factors has been well established. More recently a role for RNA binding proteins (RBPs) in regulating lifespan has also emerged. In both cases, a major challenge is to determine which regulatory targets are functionally responsible for the observed lifespan phenotype. We recently identified a pair of RBPs,exc-7/ELAVLandmbl-1/Muscleblind, which display synthetic (non-additive) lifespan defects: single mutants do not affect lifespan, butexc-7; mbl-1double mutants have strongly reduced lifespan. Such a strong synthetic phenotype represented an opportunity to use transcriptomics to search for potential causative targets that are synthetically regulated. Focus on such genes would allow us to narrow our target search by ignoring the hundreds of genes altered only in single mutants, and provide a shortlist of synthetically-regulated candidate targets that might be responsible for the double mutant phenotype. We identified a small handful of genes synthetically dysregulated in double mutants and systematically tested each candidate gene for functional contribution to theexc-7; mbl-1lifespan phenotype. We identified one such gene, the ion transporternhx-6, which is highly upregulated in double mutants. Overexpression ofnhx-6causes reduced lifespan, and deletion ofnhx-6in anexc-7; mbl-1background partially restores both lifespan and healthspan. Together, these results reveal that a pair of RBPs mediate lifespan in part by inhibiting expression of an ion transporter, and provide a template for how synthetic phenotypes (including lifespan) can be dissected at the transcriptomic level to reveal potential causative genes.