julilili42/papers huggingface dataset:
Interpretation of SD-OCT imaging data in real-life conditions versus standardized reading centre analysis in eyes with diabetic macular oedema or macular oedema secondary to retinal vein occlusion: 24-month follow-up of the ORCA study
2024-09-19

Abstract Purpose As part of the prospective, non-interventional OCEAN study, the ORCA module evaluated physicians’ spectral domain optical coherence tomography (SD-OCT) image interpretations in the treatment of diabetic macular oedema (DME) or macular oedema (ME) secondary to retinal vein occlusion (RVO). Methods Presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) was evaluated independently by physicians and reading centres (RCs) on 1612 SD-OCT scans of 133 patients diagnosed with either DME or ME secondary to RVO. Agreement between physicians and RCs was calculated for both cohorts individually and as a combined ME cohort. Physicians’ treatment decisions were analysed related to the results of the OCT-evaluations. Results For the combined ME cohort, presence of IRF/SRF was recorded by RCs in 792/1612 (49.1%) visits and by physicians in 852/1612 (52.9%) visits, with an agreement regarding presence or absence of foveal fluid in 70.4% of cases. In 64.4% (510/792) of visits with RC-detected foveal IRF and/or SRF no injection was given. In 30.3% of these visits with foveal fluid no reason was identified for a ‘watch and wait’ approach indicating possible undertreatment. BCVA deterioration was seen in a quarter of these eyes at the following visit. Conclusion Despite good agreement between physicians and RCs to recognize SRF and IRF, our data indicate that omitting injections despite foveal involvement of fluid is frequent in routine clinical practice. This may put patients at risk of undertreatment, which may negatively impact real-life BCVA outcomes. Trial registration www.clinicaltrials.gov , identifier NCT02194803.
Nuclear dualism without extensive DNA elimination in the ciliate Loxodes magnus
2024-09-19

Most eukaryotes have one nucleus and nuclear genome per cell. Ciliates have instead evolved distinct nuclei that coexist in each cell: a silent germline vs. transcriptionally active somatic nuclei. In the best-studied model species, both nuclei can divide asexually, but only germline nuclei undergo meiosis and karyogamy during sex. Thereafter, thousands of DNA segments, called internally eliminated sequences (IESs), are excised from copies of the germline genomes to produce the streamlined somatic genome. In Loxodes , however, somatic nuclei cannot divide but instead develop from germline copies even during asexual cell division, which would incur a huge overhead cost if genome editing was required. Here, we purified and sequenced both genomes in Loxodes magnus to see whether their nondividing somatic nuclei are associated with differences in genome architecture. Unlike in other ciliates studied to date, we did not find canonical germline-limited IESs, implying Loxodes does not extensively edit its genomes. Instead, both genomes appear large and equivalent, replete with retrotransposons and repetitive sequences, unlike the compact, gene-rich somatic genomes of other ciliates. Two other hallmarks of nuclear development in ciliates—domesticated DDE-family transposases and editing-associated small RNAs—were also not found. Thus, among the ciliates, Loxodes genomes most resemble those of conventional eukaryotes. Nonetheless, base modifications, histone marks, and nucleosome positioning of vegetative Loxodes nuclei are consistent with functional differentiation between actively transcribed somatic vs. inactive germline nuclei. Given their phylogenetic position, it is likely that editing was present in the ancestral ciliate but secondarily lost in the Loxodes lineage.
The Proteolytic Activity of Neutrophil-Derived Serine Proteases Bound to the Cell Surface Arming Lung Epithelial Cells for Viral Defense
2024-09-19

The collaboration between cellular proteases and host cells is pivotal in mounting an effective innate immune defense. Of particular interest is the synergistic interaction between cathepsin G (CatG) and neutrophil elastase (NE), which are proteases secreted by activated neutrophils, and the human alveolar basal epithelial cell line (A549) and the human lung epithelial-like cell line (H1299), because of the potential implications for viral infection. Our study aimed to investigate the binding capacity of CatG and NE on the surface of A549 and H1299 cells through preincubation with purified CatG and NE; thereby, the proteolytic activity could be detected using activity-based probes. Both CatG and NE were capable of binding to the cell surface and exhibited proteolytic activity, leading to increased cell surface levels of MHC I molecules, which is crucial for displaying the endogenous antigenic repertoire. In addition, CatG cleaved the S2′ site of the SARS-CoV-2 spike protein at two specific sites (815RS816 and 817FI818) as well as NE (813SK814 and 818IE819), which potentially leads to the destruction of the fusion peptide. Additionally, furin required the presence of Ca2+ ions for the distinct cleavage site necessary to generate the fusion peptide. Overall, the findings suggest that CatG and NE can fortify target cells against viral entry, underscoring the potential significance of cell surface proteases in protecting against viral invasion.
Aristotle’s Perceptual Objectivism
2024-09-19

Abstract Objectivism about perceptible qualities like colors and sounds is the view that perceptible qualities are ontologically and conceptually independent from perception. We ordinarily think of Aristotle as an objectivist about perceptible qualities – even the arch-objectivist. Yet this consensus has long been threatened by various thorny passages, including especially De anima III.2, 425b26–426a28, which appear to suggest that Aristotle is no objectivist, but a subjectivist. I show that recent attempts to make sense of these passages by appeal to Aristotle’s three-stage distinction between first potentiality, second potentiality/first actuality, and second actuality commit Aristotle to a subjectivism that he cannot consistently endorse. I argue for an alternative that vindicates Aristotle’s objectivism.
Longitudinal objective assessment of speech in Multiple Sclerosis
2024-09-19

Most individual long-term changes were small and within short-term variability intervals, irrespective of clinical disease progression. Familiarity and practice effects might have blunted the measurement of change. The present lack of longitudinal sensitivity of speech in MS contradicts previous cross-sectional findings and requires further investigation.
Humans flexibly integrate social information despite interindividual differences in reward
2024-09-20

There has been much progress in understanding human social learning, including recent studies integrating social information into the reinforcement learning framework. Yet previous studies often assume identical payoffs between observer and demonstrator, overlooking the diversity of social information in real-world interactions. We address this gap by introducing a socially correlated bandit task that accommodates payoff differences among participants, allowing for the study of social learning under more realistic conditions. Our Social Generalization (SG) model, tested through evolutionary simulations and two online experiments, outperforms existing models by incorporating social information into the generalization process, but treating it as noisier than individual observations. Our findings suggest that human social learning is more flexible than previously believed, with the SG model indicating a potential resource-rational trade-off where social learning partially replaces individual exploration. This research highlights the flexibility of humans’ social learning, allowing us to integrate social information from others with different preferences, skills, or goals.
South American monsoon intensification during the last millennium driven by joint Pacific and Atlantic forcing
2024-09-20

The South American summer monsoon (SASM) profoundly influences tropical South America’s climate, yet understanding its low-frequency variability has been challenging. Climate models and oxygen isotope data have been used to examine the SASM variability over the last millennium (LM) but have, at times, provided conflicting findings, especially regarding its mean-state change from the Medieval Climate Anomaly to the Little Ice Age. Here, we use a paleoclimate data assimilation (DA) method, combining model results and δ 18 O observations, to produce a δ 18 O-enabled, dynamically coherent, and spatiotemporally complete austral summer hydroclimate reconstruction over the LM for tropical South America at 5-year resolution. This reconstruction aligns with independent hydroclimate and δ 18 O records withheld from the DA, revealing a centennial-scale SASM intensification during the MCA-LIA transition period, associated with the southward shift of the Atlantic Intertropical Convergence Zone and the strengthening Pacific Walker circulation (PWC). This highlights the necessity of accurately representing the PWC in climate models to predict future SASM changes.
Anatomical and behavioural correlates of auditory perception in developmental dyslexia
2024-09-20

Abstract Developmental dyslexia is typically associated with difficulties in basic auditory processing and manipulating speech sounds. However, the neuroanatomical correlates of auditory difficulties in developmental dyslexia and their contribution to individual clinical phenotypes are still unknown. Recent intracranial electrocorticography findings associated processing of sound amplitude rises and speech sounds with posterior and middle superior temporal gyrus (STG), respectively. We hypothesize that regional STG anatomy will relate to specific auditory abilities in developmental dyslexia and that auditory processing abilities will relate to behavioral difficulties with speech and reading. One hundred and ten children (78 developmental dyslexia, 32 typically developing, age 7–15 years) completed amplitude rise time and speech-in-noise discrimination tasks. They also underwent a battery of cognitive tests. Anatomical MRI scans were used to identify regions in which local cortical gyrification complexity correlated with auditory behaviour. Behaviourally, amplitude rise time but not speech-in-noise performance was impaired in developmental dyslexia. Neurally, amplitude rise time and speech-in-noise performance correlated with gyrification in posterior and middle STG, respectively. Furthermore, amplitude rise time significantly contributed to reading impairments in developmental dyslexia, while speech in noise only explained variance in phonological awareness. Finally, amplitude rise time and speech-in-noise performance were not correlated, and each task was correlated with distinct neuropsychological measures, emphasizing their unique contributions to developmental dyslexia. Overall, we provide a direct link between the neurodevelopment of the left STG and individual variability in auditory processing abilities in neurotypical and dyslexic populations
Artificial intelligence based real-time prediction of imminent heart failure hospitalisation in patients undergoing non-invasive telemedicine
2024-09-20

Background Remote patient management may improve prognosis in heart failure. Daily review of transmitted data for early recognition of patients at risk requires substantial resources that represent a major barrier to wide implementation. An automated analysis of incoming data for detection of risk for imminent events would allow focusing on patients requiring prompt medical intervention. Methods We analysed data of the Telemedical Interventional Management in Heart Failure II (TIM-HF2) randomized trial that were collected during quarterly in-patient visits and daily transmissions from non-invasive monitoring devices. By application of machine learning, we developed and internally validated a risk score for heart failure hospitalisation within seven days following data transmission as estimate of short-term patient risk for adverse heart failure events. Score performance was assessed by the area under the receiver-operating characteristic (ROCAUC) and compared with a conventional algorithm, a heuristic rule set originally applied in the randomized trial. Results The machine learning model significantly outperformed the conventional algorithm (ROCAUC 0.855 vs. 0.727, p &amp;lt; 0.001). On average, the machine learning risk score increased continuously in the three weeks preceding heart failure hospitalisations, indicating potential for early detection of risk. In a simulated one-year scenario, daily review of only the one third of patients with the highest machine learning risk score would have led to detection of 95% of HF hospitalisations occurring within the following seven days. Conclusions A machine learning model allowed automated analysis of incoming remote monitoring data and reliable identification of patients at risk of heart failure hospitalisation requiring immediate medical intervention. This approach may significantly reduce the need for manual data review.
Elucidating the clinical and genetic spectrum of inositol polyphosphate phosphatase INPP4A-related neurodevelopmental disorder
2024-09-21

Our studies comprehensively characterize INPP4A-related neurodevelopmental disorder and suggest genotype-specific clinical assessment guidelines. We propose that the potential mechanistic basis of observed genotype-phenotype correlations entails exon 4 translation reinitiation.
Aberrant neuronal connectivity and network activity of neurons derived from patients with idiopathic schizophrenia
2024-09-21

Schizophrenia (SCZ) is a psychiatric disorder with a strong genetic determinant. A major hypothesis to explain disease aetiology comprises synaptic dysfunction associated with excitatory-inhibitory imbalance of synaptic transmission, ultimately contributing to impaired network oscillation and cognitive deficits associated with the disease. Here, we studied the morphological and functional properties of a highly defined co-culture of GABAergic and glutamatergic neurons derived from induced pluripotent stem cells (iPSC) from patients with idiopathic SCZ. Our results indicate upregulation of synaptic genes and increased excitatory synapse formation on GABAergic neurons in co-cultures. In parallel, we observed decreased lengths of axon initial segments, concordant with data from postmortem brains from patients with SCZ. In line with increased synapse density, patch-clamp analyses revealed markedly increased spontaneous excitatory postsynaptic currents (EPSC) recorded from GABAergic SCZ neurons. Finally, MEA recordings from neuronal networks indicate increased strength of network activity, potentially in response to altered synaptic transmission and E-I balance in the co-cultures. In conclusion, our results suggest selective deregulation of neuronal activity in SCZ samples, providing evidence for altered synapse formation and synaptic transmission as a potential base for aberrant network synchronization.
The Arabidopsis U1 snRNP regulates mRNA 3′-end processing
2024-09-23

Abstract The removal of introns by the spliceosome is a key gene regulatory mechanism in eukaryotes, with the U1 snRNP subunit playing a crucial role in the early stages of splicing. Studies in metazoans show that the U1 snRNP also conducts splicing-independent functions, but the lack of genetic tools and knowledge about U1 snRNP-associated proteins have limited the study of such splicing-independent functions in plants. Here we describe an RNA-centric approach that identified more than 200 proteins associated with the Arabidopsis U1 snRNP and revealed a tight link to mRNA cleavage and polyadenylation factors. Interestingly, we found that the U1 snRNP protects mRNAs against premature cleavage and polyadenylation within introns—a mechanism known as telescripting in metazoans—while also influencing alternative polyadenylation site selection in 3′-UTRs. Overall, our work provides a comprehensive view of U1 snRNP interactors and reveals novel functions in regulating mRNA 3′-end processing in Arabidopsis , laying the groundwork for understanding non-canonical functions of plant U1 snRNPs.
Female sex bias in Iberian megalithic societies through bioarchaeology, aDNA and proteomics
2024-09-23

Abstract Uncertainties regarding traditional osteological methods in biological sex estimation can often be overcome with genomic and proteomic analyses. The combination of the three methodologies has been used for a better understanding of the gender-related funerary rituals at the Iberian megalithic cemetery of Panoría. As a result, 44 individuals have been sexed including, for the first time, non-adults. Contrary to the male bias found in many Iberian and European megalithic monuments, the Panoría population shows a clear sex ratio imbalance in favour of females, with twice as many females as males. Furthermore, this imbalance is found regardless of the criterion considered: sex ratio by tomb, chronological period, method of sex estimation, or age group. Biological relatedness was considered as possible sociocultural explanations for this female-related bias. However, the current results obtained for Panoría are indicative of a female-centred social structure potentially influencing rites and cultural traditions.
Geographic variation in leaf traits and palatability of a native plant invader during domestic expansion
2024-09-23

Abstract Like alien plant invasion, range expansion of native plants may threaten biodiversity and economies, rendering them native invaders. Variation in abiotic and biotic conditions across a large geographic scale greatly affects variation in traits and interactions with herbivores of native plant invaders, which is an interesting yet mostly unexplored issue. We used a common garden experiment to compare defensive/nutritional traits and palatability to generalist herbivores of 20 native (23.64° N–30.18° N) and introduced range (31.58° N–36.87° N) populations of Reynoutria japonica , which is a native invader following range expansion in China. We analyzed the relationships among herbivore pressure, climate, plant chloroplast haplotypes, leaf traits, and herbivore performance. Of the 16 variables tested, we observed range differences in 11 variables and latitudinal clines in nine variables. In general, herbivores performed better on the introduced plants than on the native plants, and better on the high‐latitude plants than on the low‐latitude plants within the introduced populations. Three key traits (leaf thickness, specific leaf area, and carbon‐to‐nitrogen [C:N] ratio) determined palatability to herbivores and were significantly associated with temperature and/or precipitation of plant provenance as well as with plant haplotypes but not with herbivore pressure. Our results revealed a causal sequence from plant‐range‐based environmental forces and genetic context to plant quality and palatability to herbivores in R. japonica . These findings suggest a post‐introduction evolution of R. japonica , which may partly explain the colonization success of this important native, but invasive plant.
It takes two peroxisome proliferator-activated receptors (PPAR-β/δ and PPAR-γ) to tango idiopathic pulmonary fibrosis
2024-09-23

Abstract Background Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung epithelial phenotypes, fibroblast activation, and increased extracellular matrix deposition. Transforming growth factor-beta (TGF-β)1-induced Smad signaling and downregulation of peroxisomal genes are involved in the pathogenesis and can be inhibited by peroxisome proliferator-activated receptor (PPAR)-α activation. However, the three PPARs, that is PPAR-α, PPAR-β/δ, and PPAR-γ, are known to interact in a complex crosstalk. Methods To mimic the pathogenesis of lung fibrosis, primary lung fibroblasts from control and IPF patients with comparable levels of all three PPARs were treated with TGF-β1 for 24 h, followed by the addition of PPAR ligands either alone or in combination for another 24 h. Fibrosis markers (intra- and extracellular collagen levels, expression and activity of matrix metalloproteinases) and peroxisomal biogenesis and metabolism (gene expression of peroxisomal biogenesis and matrix proteins, protein levels of PEX13 and catalase, targeted and untargeted lipidomic profiles) were analyzed after TGF-β1 treatment and the effects of the PPAR ligands were investigated. Results TGF-β1 induced the expected phenotype; e.g. it increased the intra- and extracellular collagen levels and decreased peroxisomal biogenesis and metabolism. Agonists of different PPARs reversed TGF-β1-induced fibrosis even when given 24 h after TGF-β1. The effects included the reversals of (1) the increase in collagen production by repressing COL1A2 promoter activity (through PPAR-β/δ activation); (2) the reduced activity of matrix metalloproteinases (through PPAR-β/δ activation); (3) the decrease in peroxisomal biogenesis and lipid metabolism (through PPAR-γ activation); and (4) the decrease in catalase protein levels in control (through PPAR-γ activation) and IPF (through a combined activation of PPAR-β/δ and PPAR-γ) fibroblasts. Further experiments to explore the role of catalase showed that an overexpression of catalase protein reduced collagen production. Additionally, the beneficial effect of PPAR-γ but not of PPAR-β/δ activation on collagen synthesis depended on catalase activity and was thus redox-sensitive. Conclusion Our data provide evidence that IPF patients may benefit from a combined activation of PPAR-β/δ and PPAR-γ.
Cracking the Pericellular Matrix Code: Exploring how MMP-2, -3, and -7 influence matrix breakdown and biomechanical properties
2024-09-23

This study highlights the significant influence of MMP-induced alterations in PCM composition on biomechanical properties, mirroring characteristics observed in early OA. Each MMP showed specificity in breaking down PCM, and an intriguing interplay, especially between MMP-2 and -7, indicated reduced efficacy in lowering PCM stiffness. Overall, MMP-2, -3, and -7 directly induce functional and structural PCM modifications.
Exploring the metabolic profile of A. baumannii for antimicrobial development using genome-scale modeling
2024-09-23

With the emergence of multidrug-resistant bacteria, the World Health Organization published a catalog of microorganisms urgently needing new antibiotics, with the carbapenem-resistant Acinetobacter baumannii designated as “critical”. Such isolates, frequently detected in healthcare settings, pose a global pandemic threat. One way to facilitate a systemic view of bacterial metabolism and allow the development of new therapeutics is to apply constraint-based modeling. Here, we developed a versatile workflow to build high-quality and simulation-ready genome-scale metabolic models. We applied our workflow to create a metabolic model for A . baumannii and validated its predictive capabilities using experimental nutrient utilization and gene essentiality data. Our analysis showed that our model i ACB23LX could recapitulate cellular metabolic phenotypes observed during in vitro experiments, while positive biomass production rates were observed and experimentally validated in various growth media. We further defined a minimal set of compounds that increase A . baumannii ’s cellular biomass and identified putative essential genes with no human counterparts, offering new candidates for future antimicrobial development. Finally, we assembled and curated the first collection of metabolic reconstructions for distinct A . baumannii strains and analyzed their growth characteristics. The presented models are in a standardized and well-curated format, enhancing their usability for multi-strain network reconstruction.