julilili42/papers huggingface dataset:
Dynamics and durability of HIV-1 neutralization are determined by viral replication
2023-11-01

Abstract Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers—persons with HIV-1 who naturally develop broad and potent nAbs—can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART). Infection with non-clade B viruses, CD4 + T cell counts &lt;200 μl −1 , being off ART and a longer time off ART were independent predictors of a more potent and broad neutralization. In longitudinal analyses, we found nAb half-lives of 9.3 and 16.9 years in individuals with no- or low-level viremia, respectively, and 4.0 years in persons who newly initiated ART. Finally, in a potent HIV-1 neutralizer, we identified lower fractions of serum nAbs and of nAb-encoding memory B cells after ART initiation, suggesting that a decreasing neutralizing serum activity after antigen withdrawal is due to lower levels of nAbs. These results collectively show that HIV-1-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may elicit a durable nAb response.
Wall Teichoic Acid Mediates Staphylococcus aureus Binding to Endothelial Cells via the Scavenger Receptor LOX-1
2023-11-01

The success of <i>Staphylococcus aureus</i> as a major cause for endovascular infections depends on effective interactions with blood-vessel walls. We have previously shown that <i>S. aureus</i> uses its wall teichoic acid (WTA), a surface glycopolymer, to attach to endothelial cells. However, the endothelial WTA receptor remained unknown. We show here that the endothelial oxidized low-density lipoprotein receptor 1 (LOX-1) interacts with <i>S. aureus</i> WTA and permits effective binding of <i>S. aureus</i> to human endothelial cells. Purified LOX-1 bound to isolated <i>S. aureus</i> WTA. Ectopic LOX-1 expression led to increased binding of <i>S. aureus</i> wild type but not of a WTA-deficient mutant to a cell line, and LOX-1 blockage prevented <i>S. aureus</i> binding to endothelial cells. Moreover, WTA and LOX-1 expression levels correlated with the efficacy of the <i>S. aureus</i>-endothelial interaction. Thus, LOX-1 is an endothelial ligand for <i>S. aureus</i>, whose blockage may help to prevent or treat severe endovascular infections.
Reoxidation of Reduced Peat Organic Matter by Dissolved Oxygen: Combined Laboratory Column‐Breakthrough Experiments and In‐Field Push‐Pull Tests
2023-11-01

Abstract Electron transfer to peat particulate organic matter (POM) as terminal electron acceptor (TEA) in anaerobic respiration has been hypothesized to lower methane emissions from peatlands by competitively suppressing methanogenesis and/or allowing for anaerobic oxidation of methane. We herein provide evidence for two critical aspects of this hypothesis: (a) peat POM is present in a reduced state in situ in the anoxic peat subsurface, and (b) reduced POM at the oxic‐anoxic interface in peat soils can be oxidized by dissolved oxygen (DO), restoring its TEA capacity. We reacted reduced POM from three ombrotrophic bogs in Sweden with DO in soil‐packed column‐breakthrough experiments (CBEs), mimicking oxidation reactions at the oxic‐anoxic interface. Breakthrough of DO was substantially retarded relative to the inert tracer bromide, consistent with DO reduction by POM. Control experiments confirmed abiotic DO reduction and excluded DO consumption through aerobic respiration. Modeling DO breakthrough revealed fast and slowly reacting POM moieties with reaction times spanning minutes to days. Complementary push‐pull tests (PPTs) in the anoxic subsurface of one bog confirmed results from laboratory CBEs: lower recoveries of injected DO compared with bromide supported DO reduction by reduced POM. Rates of reduction of injected DO decreased with increasing number of injections, consistent with continuous oxidation of reduced POM. Electron‐donating capacities of POM to DO in CBEs and PPTs were comparable at 40–130 μmol e − /g dry POM. Our results substantiate that POM is a regenerable TEA at oxic‐anoxic interfaces in peat soils and, thereby, may substantially lower CH 4 emissions from peatlands.
Bridging the Gap Between Experimental and Natural Fabrics: Modeling Ice Stream Fabric Evolution and its Comparison With Ice‐Core Data
2023-11-01

Abstract Fabrics, also known as textures or crystallographic preferred orientations, reveal information about the deformation history of the flow of polycrystalline materials, including glacial ice, olivine in the mantle, and feldspar and quartz in the crust. Ice fabrics can have an order‐of‐magnitude effect on the ease of flow in ice sheets. However, due to the choice of ice core drill site locations, the outputs of fabric models have mostly been compared to observations from the least dynamic regions of the ice sheet (ice divides). Recently, fabric data from an active ice stream have become available from ice cores drilled at the East Greenland Ice‐core Project (EGRIP). In this work, we present a novel approach that combines satellite‐derived velocity data with the fabric evolution model SpecCAF, a continuum model based on dominant dislocation creep. We directly compare model output to ice‐core observations from EGRIP, allowing us to examine the quantitative predictions of calibrated fabric models alongside those of active ice streams for the first time. As the model is calibrated against laboratory experiments, it provides a surrogate to compare the evolution of fabrics under laboratory and natural conditions. The predictions show good qualitative agreement with the observed fabric patterns and orientations, suggesting that a fabric between a girdle and horizontal maximum, orientated perpendicular to the flow direction, is the characteristic ice stream fabric. A discrepancy in fabric strength is attributed to the lower strain rates of ice sheets compared to laboratory experiments, revealing a significant strain‐rate dependence in the processes controlling fabric evolution.
Body Dissatisfaction Directs Avatar Perception: Embodiment and Selective Visual Attention in Body Mass-Modified Self-Avatars
2023-11-01

Human agents immersed in metaverse technologies such as virtual reality (VR) are routinely disconnected from their actual physical appearance and embodied in another virtual body, referred to as self-avatar. Such body transformations can have implications for patients with eating disorders, or persons with extreme body dissatisfaction (BD). Changes in BD, weight anxiety, or body image are theoretically linked to visual selective attention, which can be measured with eye tracking. In the present study, 43 women with high or low BD were immersed in animated body weight-manipulated self-avatars in VR. Before a brief mirror exposure with their self-avatars, they experienced synchronous visuomotor and visuo-tactile contingencies in VR to increase embodiment, delivered through small movement exercises with real-time animation from first-person perspective and passive haptics. In a crossover study design, self-avatar weight was manipulated (normal weight vs. overweight) in both groups (low BD vs. high BD), and subjective experience was assessed before and after exposure. In contrast to our hypotheses, BD was not affected by the self-avatar condition. Embodiment decreased during mirror exposure, possibly due to the avatars wearing head-mounted displays. Interestingly, disembodiment was stronger in women with low BD. Furthermore, eye tracking showed that participants with high BD looked longer at weight-related body parts when immersed in the overweight self-avatar, whereas participants with low BD looked longer at weight-related body parts when immersed in the normal weight self-avatar. Overall, the results support body-specific visual attention and suggest that particularly participants with low BD show stronger disembodiment during self-avatar mirror exposure, possibly alleviating momentary body experience. Preregistration: https://doi.org/10.23668/psycharchives.4949.
Pluripotent stem cell-derived neural progenitor cells can be used to model effects of IL-6 on human neurodevelopment
2023-11-01

ABSTRACT Maternal immune activation (MIA) increases the risks for neurodevelopmental disorders in offspring through inflammatory cytokines, including interleukin-6 (IL-6). We therefore aimed to establish a human two-dimensional (2D) in vitro neural model to investigate the effects of IL-6 exposure on neurodevelopment. IL-6 signal transduction requires two receptors: interleukin-6 signal transducer (IL6ST) and interleukin-6 receptor (IL6R). Prenatally, neural cells lack IL6R, and hence cannot elicit cis IL-6 signaling, but IL6R can be provided by microglia in trans. We demonstrate here that an immortalized human neural progenitor cell (NPC) line, ReNCell CX, expresses IL6ST and elicits both cis and trans IL-6 signaling, limiting its use as a model of MIA. In contrast, induced pluripotent stem cell (iPSC)-derived NPCs only activate the IL-6 cascade in trans. Activation of the trans IL-6 cascade did not result in increased proliferation of iPSC-derived NPCs or ReNCell CX, as has been demonstrated in animal models. iPSC-derived NPCs upregulated NR2F1 expression in response to IL-6 signaling in line with analogous experiments in organoids. Thus, iPSC-derived NPCs can be used to model gene expression changes in response to MIA in 2D cultures.
Evaluating the impact of COVID-19 pandemic-related home confinement on the refractive error of school-aged children in Germany: a cross-sectional study based on data from 414 eye care professional centres
2023-11-01

Objective This study aimed at evaluating refractive changes in German school-aged children before and after the COVID-19 pandemic. Design Cross-sectional study. Setting 414 eye care professional centres from Germany. Participants Refractive data from 59 926 German children aged 6–15 years were examined over a 7-year period (2015–2021). Primary and secondary outcome measures Spherical equivalent refraction was assessed as a function of year, age and gender. The refractive values concerning 2020 and 2021 were compared with those assigned to prior years (2015–2019). Results The refractive data associated with 2020 and 2021 showed a myopic refractive shift of approximately −0.20D compared with the 2015–2019 range. The refractive change was statistically considerable in the 6 to 11-year range (p&lt;0.05), while from 12 to 15 years was negligible (p≥0.10). Percentage of myopes was also impacted in 2021 (p=0.002), but not in 2020 (p=0.25). From 6 to 11 years, the percentage of myopes in 2021 increased significantly by 6.02% compared with the 2015–2019 range (p≤0.04). The highest percentage increase occurred at 8 and 10 years of age, showing a rise of 7.42% (p=0.002) and 6.62% (p=0.005), respectively. From 12 to 15 years, there was no significant increase in the percentage of myopes in 2021 (p≥0.09). Percentage of myopes in 2020 was not influenced at any age (p≥0.06). Conclusion Disruption of normal lifestyle due to pandemic-related home confinement appears to lead to a myopic refractive shift in children aged 6–11 years in Germany. The greater effect observed at younger ages seems to emphasise the importance of refractive development in this age group.
The first European woolly rhinoceros mitogenomes, retrieved from cave hyena coprolites, suggest long-term phylogeographic differentiation
2023-11-01

The woolly rhinoceros ( Coelodonta antiquitatis ) is an iconic species of the Eurasian Pleistocene megafauna, which was abundant in Eurasia in the Pleistocene until its demise beginning approximately 10 000 years ago. Despite the early recovery of several specimens from well-known European archaeological sites, including its type specimen (Blumenbach 1799), no genomes of European populations were available so far, and all available genomic data originated exclusively from Siberian populations. Using coprolites of cave hyenas ( Crocuta crocuta spelea ) recovered from Middle Palaeolithic layers of two caves in Germany (Bockstein-Loch and Hohlenstein-Stadel), we isolated and enriched predator and prey DNA to assemble the first European woolly rhinoceros mitogenomes, in addition to cave hyena mitogenomes. Both coprolite samples produced copious sequences assigned to C. crocuta (27% and 59% mitogenome coverage, respectively) and woolly rhinoceros ( Coelodonta antiquitatis ; 27% and 81% coverage, respectively). The sequences suggested considerable DNA degradation, which may limit the conclusions to be drawn; however, the mitogenomes of European woolly rhinoceros are genetically distinct from the Siberian woolly rhinoceros, and analyses of the more complete mitogenome suggest a split of the populations potentially coinciding with the earliest fossil records of woolly rhinoceros in Europe.
Relationships between ecosystem functions vary among years and plots and are driven by plant species richness
2023-11-01

Ecosystem management aims at providing many ecosystem services simultaneously. Such ecosystem service multifunctionality can be limited by tradeoffs and increased by synergies among the underlying ecosystem functions (EF), which need to be understood to develop targeted management. Previous studies found differences in the correlation between EFs. We hypothesised that correlations between EFs are variable even under the controlled conditions of a field experiment and that seasonal and annual variation, plant species richness, and plot identity (identity effects of plots, such as the presence and proportion of functional groups) are drivers of these correlations. We used data on 31 EFs related to plants, consumers, and physical soil properties that were measured over 5 to 19 years, up to three times per year, in a temperate grassland experiment with 80 different plots, constituting six sown plant species richness levels (1, 2, 4, 8, 16, 60 species). We found that correlations between pairs of EFs were variable, and correlations between two particular EFs could range from weak to strong or negative to positive correlations among the repeated measurements. To determine the drivers of pairwise EF correlations, the covariance between EFs was partitioned into contributions from species richness, plot identity, and time (including years and seasons). We found that most of the covariance for synergies was explained by species richness (26.5%), whereas for tradeoffs, most covariance was explained by plot identity (29.5%). Additionally, some EF pairs were more affected by differences among years and seasons, showing a higher temporal variation. Therefore, correlations between two EFs from single measurements are insufficient to draw conclusions on tradeoffs and synergies. Consequently, pairs of EFs need to be measured repeatedly under different conditions to describe their relationships with more certainty and be able to derive recommendations for the management of grasslands.
The Aggregation of ROAD Data in the ARIADNE Pipeline: pitfalls and successes
2023-11-01

In this article we describe an online database about human evolution, called the ROCEEH Out of Africa Database (ROAD), and discuss our experience in aggregating Palaeolithic data from ROAD in the ARIADNE data processing pipeline. As of April 2023, ROAD contains more than 2400 localities in Africa and Eurasia dating between three million and 20,000 years ago. The database is transdisciplinary by nature and includes cultural artefacts, human and animal fossils, and plant remains. These finds are stored in a relational database, which is part of a structured, web-based, geographic information system. The process of preparing ROAD data for integration with ARIADNE taught us lessons about our own dataset, which we share here.
CTIM-25. EO2401 PEPTIDE IMMUNOTHERAPY + NIVOLUMAB +/- BEVACIZUMAB IN FIRST RECURRENT GLIOBLASTOMA: THE PHASE 1/2 EOGBM1-18/ROSALIE STUDY (NCT04116658)
2023-11-01

Abstract EO2401 expands existing memory T cells recognizing protein sequences from gut bacteria, which cross-react with tumor associated antigens (TAAs). EO2401 contains three CD8 HLA-A2 epitopes with mimicry to glioblastoma-TAAs (IL13Rα2, BIRC5, and FOXM1) and the CD4 epitope UCP2. Patients received EO2401 (300μg/peptide, q2weeks x4, then every 4weeks) with nivolumab (3mg/kg, q2weeks) in cohorts: C1a (n = 21, Ex2→EN; option for symptom directed low-dose bevacizumab [sLDB; 5mg/kg, q2weeks] as anti-edema treatment); C2a/1 (n = 23, EN); C2a/2 (n = 15, EN+sLDB); C2b (n = 6, adjuvant EN+sLDB); C2c (n = 9, neoadjuvant ENx2→surgery→adjuvant EN+sLDB); C3 (n = 26, EN+bevacizumab, q2weeks, 10mg/kg). EO2401/nivolumab+/-bevacizumab safety profile consistent with profile of nivolumab, and when applicable bevacizumab, except the addition of local administration site reactions which occurred in 39% of patients; 96% of events Grade 1/2 and 4% Grade 3. Immune monitoring (peripheral blood, ELISPOT, tetramer assessments) demonstrated expanded mimic specific CD8 T cells with cross-reactivity against the targeted human TAAs. In C2a/1 (83% tested) and in C3 (81% tested), 89% and 95% of tested patients showed expansion. Expansions were early (week 2 after starting EO2401), durable (up to 23 months), and robust (approximately 30% of all peripheral CD8 T cells were mimic specific in 3 clinical responders). In C2c, surgery specimens after two EO2401/nivolumab doses showed increased tumor T cell infiltration versus pre-treatment tumor in 5 of 6 patients. Addition of sLDB to EO2401/nivolumab prolonged treatment duration vs EO2401/nivolumab alone by reducing edema likely worsened by study therapy induced immune cell infiltration. Integration of bevacizumab with EO2401/nivolumab in C3 further increased efficacy in C3. C2a/1vsC2a/2vsC3: median treatment duration 1.4vs3.2vs4.8 months, disease control rate 22%vs40%vs88%, median PFS 1.6vs3.6vs5.5 months; median survival 9.0vs12.6vstoo early (C3 median FU 8.3 mo, survival ongoing up to 2 years). Further follow-up will be presented.
Point-of-Care Ultrasound for Tuberculosis in Young Children with Severe Acute Malnutrition
2023-11-01

Point-of-care ultrasound (POCUS) to diagnose tuberculosis (TB) was assessed in 131 children under 5 years old hospitalized with severe acute malnutrition. Of these, 23% had confirmed or unconfirmed TB and 5% were HIV-infected. There were no POCUS findings associated with TB diagnosis. POCUS visualization quality was satisfactory for 65% and examination acceptability was “good” for 52%.
Increasing hub disruption parallels dementia severity in autosomal dominant Alzheimer disease
2023-11-01

Abstract Hub regions in the brain, recognized for their roles in ensuring efficient information transfer, are vulnerable to pathological alterations in neurodegenerative conditions, including Alzheimer Disease (AD). Given their essential role in neural communication, disruptions to these hubs have profound implications for overall brain network integrity and functionality. Hub disruption, or targeted impairment of functional connectivity at the hubs, is recognized in AD patients. Computational models paired with evidence from animal experiments hint at a mechanistic explanation, suggesting that these hubs may be preferentially targeted in neurodegeneration, due to their high neuronal activity levels—a phenomenon termed “activity-dependent degeneration”. Yet, two critical issues were unresolved. First, past research hasn’t definitively shown whether hub regions face a higher likelihood of impairment (targeted attack) compared to other regions or if impairment likelihood is uniformly distributed (random attack). Second, human studies offering support for activity-dependent explanations remain scarce. We applied a refined hub disruption index to determine the presence of targeted attacks in AD. Furthermore, we explored potential evidence for activity-dependent degeneration by evaluating if hub vulnerability is better explained by global connectivity or connectivity variations across functional systems, as well as comparing its timing relative to amyloid beta deposition in the brain. Our unique cohort of participants with autosomal dominant Alzheimer Disease (ADAD) allowed us to probe into the preclinical stages of AD to determine the hub disruption timeline in relation to expected symptom emergence. Our findings reveal a hub disruption pattern in ADAD aligned with targeted attacks, detectable even in pre-clinical stages. Notably, the disruption’s severity amplified alongside symptomatic progression. Moreover, since excessive local neuronal activity has been shown to increase amyloid deposition and high connectivity regions show high level of neuronal activity, our observation that hub disruption was primarily tied to regional differences in global connectivity and sequentially followed changes observed in Aβ PET cortical markers is consistent with the activity-dependent degeneration model. Intriguingly, these disruptions were discernible 8 years before the expected age of symptom onset. Taken together, our findings not only align with the targeted attack on hubs model but also suggest that activity-dependent degeneration might be the cause of hub vulnerability. This deepened understanding could be instrumental in refining diagnostic techniques and developing targeted therapeutic strategies for AD in the future.
Comparison of the saccules and lagenae in six macrourid fishes from different deep-sea habitats
2023-11-01

There are substantial interspecific differences in the morphology of the ears of the more than 34 000 living fish species. However, almost nothing is known about the functional significance of these differences. One reason is that most comparative studies have been conducted on shallow-water species with far less focus on the numerous species that inhabit the depths of the oceans. Thus, to get a better sense of ear diversity in fishes and its potential role in hearing, this study focuses on the saccule and lagena, the primary auditory end organs, in six species of the family Macrouridae (rattails), a large group of fishes that typically inhabit depths from 1000 to 4000 m. The inner ears and, particularly, the saccules and lagenae in these species are large with the saccule resembling that of other Gadiformes. The lagenae of all macrourids studied here have serrated edge otoliths and highly diverse hair cell ciliary bundle shapes. The differences found in the inner ear anatomy of macrourids likely reflect the sensory advantages in different habitats that are related to the benefits and constraints at different depths, the fish's particular lifestyle, and the trade-off among different sensory systems.