julilili42/papers huggingface dataset:
The Acute, Short-, and Long-Term Effects of Endurance Exercise on Skeletal Muscle Transcriptome Profiles
2024-03-01

A better understanding of the cellular and molecular mechanisms that are involved in skeletal muscle adaptation to exercise is fundamentally important to take full advantage of the enormous benefits that exercise training offers in disease prevention and therapy. The aim of this study was to elucidate the transcriptional signatures that distinguish the endurance-trained and untrained muscles in young adult males (24 ± 3.5 years). We characterized baseline differences as well as acute exercise-induced transcriptome responses in vastus lateralis biopsy specimens of endurance-trained athletes (ET; n = 8; VO2max, 67.2 ± 8.9 mL/min/kg) and sedentary healthy volunteers (SED; n = 8; VO2max, 40.3 ± 7.6 mL/min/kg) using microarray technology. A second cohort of SED volunteers (SED-T; n = 10) followed an 8-week endurance training program to assess expression changes of selected marker genes in the course of skeletal muscle adaptation. We deciphered differential baseline signatures that reflected major differences in the oxidative and metabolic capacity of the endurance-trained and untrained muscles. SED-T individuals in the training group displayed an up-regulation of nodal regulators of oxidative adaptation after 3 weeks of training and a significant shift toward the ET signature after 8 weeks. Transcriptome changes provoked by 1 h of intense cycling exercise only poorly overlapped with the genes that constituted the differential baseline signature of ETs and SEDs. Overall, acute exercise-induced transcriptional responses were connected to pathways of contractile, oxidative, and inflammatory stress and revealed a complex and highly regulated framework of interwoven signaling cascades to cope with exercise-provoked homeostatic challenges. While temporal transcriptional programs that were activated in SEDs and ETs were quite similar, the quantitative divergence in the acute response transcriptomes implicated divergent kinetics of gene induction and repression following an acute bout of exercise. Together, our results provide an extensive examination of the transcriptional framework that underlies skeletal muscle plasticity.
Scorpionfish adjust skin pattern contrast on different backgrounds
2024-03-01

Abstract The two scorpionfish species Scorpaena maderensis and S. porcus are well camouflaged ambush predators that rapidly change body colouration to adjust to background colour in less than 1 min. We tested whether individuals of both species also adjust body pattern to that of the background. We placed fish on backgrounds of different pattern granularity and quantified the change in fish body pattern over 1 min. We used calibrated image analysis to analyse the patterns from the visual perspective of a prey fish species using a granularity (pattern energy) analysis and an image clustering approach. In our experiment, fish did not change their most contrasting pattern components as defined by the dominant marking size, but changed their average marking size. Moreover, fish responded with a change in pattern in contrast to the different experimental backgrounds, especially when compared to the acclimation phase. These results indicate that scorpionfish have one main pattern that can be adjusted by modulating its internal contrast. A reduction in pattern contrast could thereby improve background matching, while an increase could promote camouflage via disruptive colouration.
Proteomic workflows for deep phenotypic profiling of 3D organotypic liver models
2024-03-01

Abstract Organotypic human tissue models constitute promising systems to facilitate drug discovery and development. They allow to maintain native cellular phenotypes and functions, which enables long‐term pharmacokinetic and toxicity studies, as well as phenotypic screening. To trace relevant phenotypic changes back to specific targets or signaling pathways, comprehensive proteomic profiling is the gold‐standard. A multitude of proteomic workflows have been applied on 3D tissue models to quantify their molecular phenotypes; however, their impact on analytical results and biological conclusions in this context has not been evaluated. The performance of twelve mass spectrometry‐based global proteomic workflows that differed in the amount of cellular input, lysis protocols and quantification methods was compared for the analysis of primary human liver spheroids. Results differed majorly between protocols in the total number and subcellular compartment bias of identified proteins, which is particularly relevant for the reliable quantification of transporters and drug metabolizing enzymes. Using a model of metabolic dysfunction‐associated steatotic liver disease, we furthermore show that critical disease pathways are robustly identified using a standardized high throughput‐compatible workflow based on thermal lysis, even using only individual spheroids (1500 cells) as input. The results increase the applicability of proteomic profiling to phenotypic screens in organotypic microtissues and provide a scalable platform for deep phenotyping from limited biological material.
Patrilocality at the Beginning of Farming? An Isotopic Approach from SE Moravia
2024-03-01

Abstract This research combines Strontium ( 87 Sr/ 86 Sr) and Oxygen ( δ 18 O) isotope analysis to challenge the prevailing interpretation of patrilocal exogamic practices among eastern European Early Neolithic Linearbandkeramik (LBK) communities. Patrilocality has been considered the key factor influencing the mobility patterns of central Europe’s first farmers (c. 5500–4900 cal. BC), especially in the south-eastern Moravian region (Czech Republic). Focusing our attention on both male and female tooth enamel samples from cemeteries, settlement graves and small clusters of graves, this paper reassesses the correlation between mobility, biological sex, and funerary practices. This task is accomplished by establishing a new isotopic footprint using new 87 Sr/ 86 Sr data, as well as significantly increasing the number of sampled individuals for 87 Sr/ 86 Sr and δ 18 O. The outcome of this research contributes to a better understanding of the mobility patterns among early farmers in central Europe, challenging existing theories and providing new insights into their social and cultural dynamics.
Practice Recommendations or Not? The LoGeT Model as Empirical Approach to Generate Localized, Generalized, and Transferable Evidence
2024-03-01

Abstract In educational research, there is the general trade-off that empirical evidence should be generalizable to be applicable across contexts; at the same time, empirical evidence should be as specific as possible to be localizable in subject-specific educational interventions to successfully transfer the empirical evidence to educational practice. This trade-off is further increased by the fact that the diverse instructional contexts, such as school or student characteristics constrain the applicability of empirical evidence. Several approaches have been proposed to address this issue, however, emphasized the different problems (i.e., localization, generalization, transferability) rather in an isolated manner. To this end, in this article, we introduce a synergistic approach, the LoGeT (localize, generalize, transfer) model, which systematically integrates co-design (localization strategies) and ManyClasses principles (generalization strategies) with co-constructive transfer activities, to generate empirical evidence that may be applicable in educational practice. To illustrate the LoGeT model, we present three long-term projects, covering different granularities and durations of educational interventions across different fields of education (teacher education, adaptive teaching, non-interactive teaching) that successfully applied the LoGeT approach. Finally, we outline further directions for future iterations of the LoGeT model. We hope that the LoGeT approach may be a stimulus to guide researchers as well as practitioners alike to design generalizable and evidence-based educational interventions that are rooted in localized instructional contexts.
RPE65-Associated Retinal Dystrophies: Phenotypes and Treatment Effects with Voretigene Neparvovec
2024-03-01

Abstract Retinal dystrophies linked to the RPE65 gene are mostly fast-progressing retinal diseases, with childhood onset of night blindness and progressive visual loss up to the middle adult age. Rare phenotypes linked to this gene are known with congenital stationary night blindness or slowly progressing retinitis pigmentosa, as well as an autosomal dominant c.1430A&gt;G (p.Asp477Gly) variant. This review gives an overview of the current knowledge of the clinical phenotypes, as well as experience with the efficacy and safety of the approved gene augmentation therapy voretigene neparvovec.
TeV flaring activity of the AGN PKS 0625–354 in November 2018
2024-03-01

Most γ -ray detected active galactic nuclei are blazars with one of their relativistic jets pointing towards the Earth. Only a few objects belong to the class of radio galaxies or misaligned blazars. Here, we investigate the nature of the object PKS 0625−354, its γ -ray flux and spectral variability and its broad-band spectral emission with observations from H.E.S.S., Fermi -LAT, Swift -XRT, and UVOT taken in November 2018. The H.E.S.S. light curve above 200 GeV shows an outburst in the first night of observations followed by a declining flux with a halving time scale of 5.9 h. The γγ -opacity constrains the upper limit of the angle between the jet and the line of sight to ∼10°. The broad-band spectral energy distribution shows two humps and can be well fitted with a single-zone synchrotron self Compton emission model. We conclude that PKS 0625−354, as an object showing clear features of both blazars and radio galaxies, can be classified as an intermediate active galactic nuclei. Multi-wavelength studies of such intermediate objects exhibiting features of both blazars and radio galaxies are sparse but crucial for the understanding of the broad-band emission of γ -ray detected active galactic nuclei in general.
Multiwavelength Pulsations and Surface Temperature Distribution in the Middle-aged Pulsar B1055–52
2024-03-01

Abstract We present a detailed study of the X-ray emission from PSR B1055–52 using XMM-Newton observations from 2019 and 2000. The phase-integrated X-ray emission from this pulsar is poorly described by existing models of neutron star atmospheres. Instead, we confirm that, similar to other middle-aged pulsars, the best-fitting spectral model consists of two blackbody components, with substantially different temperatures and emitting areas, and a nonthermal component characterized by a power law. Our phase-resolved X-ray spectral analysis using this three-component model reveals variations in the thermal emission parameters with the pulsar’s rotational phase. These variations suggest a nonuniform temperature distribution across the neutron star’s surface, including the cold thermal component and probable hot spot(s). Such a temperature distribution can be caused by external and internal heating processes, likely a combination thereof. We observe very high pulse fractions, 60%–80% in the 0.7–1.5 keV range, dominated by the hot blackbody component. This could be related to temperature nonuniformity and potential beaming effects in an atmosphere. We find indication of a second hot spot that appears at lower energies (0.15–0.3 keV) than the first hot spot (0.5–1.5 keV) in the X-ray light curves and is offset by about half a rotation period. This finding aligns with the nearly orthogonal rotator geometry suggested by radio observations of this interpulse pulsar. If the hot spots are associated with polar caps, a possible explanation for their temperature asymmetry could be an offset magnetic dipole and/or an additional toroidal magnetic field component in the neutron star crust.
The neuroanatomy of visual extinction following right hemisphere brain damage: Insights from multivariate and Bayesian lesion analyses in acute stroke
2024-03-01

Abstract Multi‐target attention, that is, the ability to attend and respond to multiple visual targets presented simultaneously on the horizontal meridian across both visual fields, is essential for everyday real‐world behaviour. Given the close link between the neuropsychological deficit of extinction and attentional limits in healthy subjects, investigating the anatomy that underlies extinction is uniquely capable of providing important insights concerning the anatomy critical for normal multi‐target attention. Previous studies into the brain areas critical for multi‐target attention and its failure in extinction patients have, however, produced heterogeneous results. In the current study, we used multivariate and Bayesian lesion analysis approaches to investigate the anatomical substrate of visual extinction in a large sample of 108 acute right hemisphere stroke patients. The use of acute stroke patient data and multivariate/Bayesian lesion analysis approaches allowed us to address limitations associated with previous studies and so obtain a more complete picture of the functional network associated with visual extinction. Our results demonstrate that the right temporo‐parietal junction (TPJ) is critically associated with visual extinction. The Bayesian lesion analysis additionally implicated the right intraparietal sulcus (IPS), in line with the results of studies in neurologically healthy participants that highlighted the IPS as the area critical for multi‐target attention. Our findings resolve the seemingly conflicting previous findings, and emphasise the urgent need for further research to clarify the precise cognitive role of the right TPJ in multi‐target attention and its failure in extinction patients.
Surgical Procedures for the Treatment of Stress Urinary Incontinence (SUI) in the Light of the Updated FDA-Warning and its Effects on Practice Patterns in Germany between 2010 and 2021
2024-03-01

Abstract Changes in surgical practice patterns to cure stress urinary incontinence (SUI) became evident after FDA warnings regarding vaginal mesh were issued. The primary aim was to describe nationwide numbers of suburethral alloplastic slings (SAS) inserted in 2010, 2015, 2018 and 2021 in Germany. Secondary, numbers were related to SUI specific non-alloplastic alternatives and bulking agents. Additionally, age distribution and overall inpatient surgeries in women were subject to analysis. Descriptive study utilizing data gathered from the German Federal Statistical Office (www.destatis.de). Included were the following procedures of inpatient surgery: A. SAS; B. non-allplastic slings; C. open/laparoscopic colposuspension; D. Bulking agents; overall changes and changes in age distribution (groups of 5-years intervals) are described. Overall, n = 3599466 female inpatient procedures were analyzed. There was a considerable decrease of SAS surgeries of 28.49% between 2010 (n = 23464) and 2015 (n = 16778), and a decrease of 12.42% between 2015 and 2018 (n = 14695) and an additional decrease of 40.66% between 2018 and 2021 (n = 8720). Over time a 55.03% continuous decrease in non-alloplastic slings was observed (n = 725 in 2010 to n = 326 in 2021). Open and laparoscopic colposuspension numbers went down with a rate of 58.23% (n = 4415 in 2010, n = 1844 in 2021). Between 2010 and 2018, only bulking agent procedures increased with a rate of 5.89% from n = 1425 to n = 1509. There was a considerable decrease in inpatient surgical procedures using SAS. Alternatives not only failed to compensate, but experienced also a major decline.
Metabolic rewiring enables ammonium assimilation via a non‐canonical fumarate‐based pathway
2024-03-01

Abstract Glutamate serves as the major cellular amino group donor. In Bacillus subtilis , glutamate is synthesized by the combined action of the glutamine synthetase and the glutamate synthase (GOGAT). The glutamate dehydrogenases are devoted to glutamate degradation in vivo. To keep the cellular glutamate concentration high, the genes and the encoded enzymes involved in glutamate biosynthesis and degradation need to be tightly regulated depending on the available carbon and nitrogen sources. Serendipitously, we found that the inactivation of the ansR and citG genes encoding the repressor of the ansAB genes and the fumarase, respectively, enables the GOGAT‐deficient B. subtilis mutant to synthesize glutamate via a non‐canonical fumarate‐based ammonium assimilation pathway. We also show that the de‐repression of the ansAB genes is sufficient to restore aspartate prototrophy of an aspB aspartate transaminase mutant. Moreover, in the presence of arginine, B. subtilis mutants lacking fumarase activity show a growth defect that can be relieved by aspB overexpression, by reducing arginine uptake and by decreasing the metabolic flux through the TCA cycle.
Reanalysis of Immunopeptidomics Datasets Provides Mechanistic Insight into TAPBPR-Mediated Peptide Editing on HLA-A, -B and -C Molecules
2024-03-01

<ns3:p>Background Major histocompatibility class I (MHC-I, human leukocyte antigen [HLA]-I in humans) molecules present small fragments of the proteome on the cell surface for immunosurveillance, which is pivotal to control infected and malignant cells. Immunogenic peptides are generated and selected in the MHC-I antigen processing and presentation pathway. In this pathway, two homologous molecules, tapasin and TAPBPR, optimise the MHC-I peptide repertoire that is ultimately presented at the plasma membrane. Peptide exchange on HLA-I by human TAPBPR involves the flexible loop region K22-D35, with the leucine at position 30 (L30) involved in mediating peptide dissociation. However, our understanding of the exact molecular mechanisms governing TAPBPR-mediated peptide exchange on HLA-I allotypes remains incomplete. Methods Here, in-depth re-analyses of published immunopeptidomics datasets was used to further examine TAPBPR peptide editing activity and mechanism of action on HLA-I. The role of the TAPBPR editing loop in opening the HLA-I peptide binding groove was assessed using a molecular dynamics simulation. Results We show that TAPBPR shapes the peptide repertoire on HLA-A, -B and -C allotypes. The TAPBPR editing loop was not essential to allow HLA-I to adopt an open state. L30 in the TAPBPR editing loop was typically sufficient to mediate peptide repertoire restriction on the three HLA-I allotypes expressed by HeLa cells. TAPBPR was also able to load peptides onto HLA-I in a loop-dependent manner. Conclusions These results unify the previously hypothesised <ns3:italic>scoop loop</ns3:italic> and <ns3:italic>peptide trap</ns3:italic> mechanisms of TAPBPR-mediated peptide exchange, with the former involved in peptide filtering and the latter in peptide loading.</ns3:p>
Alpha-180 spin-echo-based line-scanning method for high-resolution laminar-specific fMRI in animals
2024-03-01

Abstract Laminar-specific functional magnetic resonance imaging (fMRI) has been widely used to study circuit-specific neuronal activity by mapping spatiotemporal fMRI response patterns across cortical layers. Hemodynamic responses reflect indirect neuronal activity given the limitation of spatial and temporal resolution. Previously, a gradient-echo-based line-scanning fMRI (GELINE) method was proposed with high temporal (50 ms) and spatial (50 μm) resolution to better characterize the fMRI onset time across cortical layers by employing two saturation RF pulses. However, the imperfect RF saturation performance led to poor boundary definition of the reduced region of interest (ROI) and aliasing problems outside of the ROI. Here, we propose an α (alpha)-180 spin-echo-based line-scanning fMRI (SELINE) method in animals to resolve this issue by employing a refocusing 180 ̊ RF pulse perpendicular to the excitation slice (without any saturation RF pulse) and also achieve high spatiotemporal resolution. In contrast to GELINE signals which peaked at the superficial layer, we detected varied peaks of laminar-specific BOLD signals across deeper cortical layers using the SELINE method, indicating the well-defined exclusion of the large draining-vein effect using the spin-echo sequence. Furthermore, we applied the SELINE method with a 200 ms repetition time (TR) to sample the fast hemodynamic changes across cortical layers with a less draining vein effect. In summary, this SELINE method provides a novel acquisition scheme to identify microvascular-sensitive laminar-specific BOLD responses across cortical depth.
How to establish a successful and sustainable surgical atrial fibrillation program: key considerations on the arrhythmia, training and treatment strategies
2024-03-01

Establishing a successful and sustaining atrial fibrillation (AF) program should be current standard of care in cardiac surgery by providing not only sinus rhythm restoration but improving survival significantly. Recognition of AF as a serious cardiac disease impacting a considerable number of patients in terms of stroke, heart failure development and mortality is key when implementing a protocol to identify patients suitable for surgical ablation and a treatment standard according to the underlying pathology. The ablation strategy resulting in the best potential rhythm outcome should be chosen, and the applied access should follow this decision in a way that the optimal lesion set can be executed completely. A thorough follow-up is required to confirm results or make necessary adjustments to the implemented treatment protocol. This should be done in close collaboration with other treatment specialists such as cardiologists, electrophysiologists, primary care physicians, or neurologists. This collaboration might also facilitate an expansion of the program towards stand-alone ablation, ventricular tachycardia ablation, and inappropriate sinus tachycardia ablation.
The inter-relationship between word learning, native phonology and production practice through cross-situational statistics
2024-03-01

Non-native speakers may have difficulty in learning words with non-native sound sequences (e.g., Flege &amp;amp; Bohn, 2021). Furthermore, the extent to which knowledge obtained from practising one skill, such as listening, may transfer to another skill, such as speaking, is a contentious debate (e.g., Li &amp;amp; DeKeyser, 2017). We investigated how native phonology and production practice affects comprehension and speech production of novel non-native words. We used a cross-situational learning paradigm (CSL) to train native speakers of English on pseudowords containing a non-native European Portuguese nasal vowel. The effect of comprehension versus production practice was manipulated to measure the effect of task modality on learning words containing native and non-native sounds. In the CSL task, comprehension improved but pseudoword repetition accuracy declined over training.We observed no effect of task modality in the CSL task or the comprehension test, except a significant effect of production practice on accuracy in the production test. There was also no effect of native phonology in either the CSL task or the comprehension test. There was, however, a significant learning effect of nasal word types in the main analysis of the production test, contrary to our predictions. Our general findings support the robustness of CSL for novel word comprehension, rather than word production performance.