julilili42/papers huggingface dataset:
SLUSH peptides of the PSMβ family enable Staphylococcus lugdunensis to use erythrocytes as a sole source of nutrient iron
2024-08-21

Abstract During infection, the host employs nutritional immunity to restrict access to iron. Staphylococcus lugdunensis has been recognized for its ability to utilize host‐derived heme to overcome iron restriction. However, the mechanism behind this process involves the release of hemoglobin from erythrocytes, and the hemolytic factors of S. lugdunensis remain poorly understood. S. lugdunensis encodes four phenol‐soluble modulins (PSMs), short peptides with hemolytic activity. The peptides SLUSH A, SLUSH B, and SLUSH C are β‐type PSMs, and OrfX is an α‐type PSM. Our study shows the SLUSH locus to be essential for the hemolytic phenotype of S. lugdunensis . All four peptides individually exhibited hemolytic activity against human and sheep erythrocytes, but synergism with sphingomyelinase was observed exclusively against sheep erythrocytes. Furthermore, our findings demonstrate that SLUSH is crucial for allowing the utilization of erythrocytes as the sole source of nutritional iron and confirm the transcriptional regulation of SLUSH by Agr. Additionally, our study reveals that SLUSH peptides stimulate the human immune system. Our analysis identifies SLUSH as a pivotal hemolytic factor of S. lugdunensis and demonstrates its concerted action with heme acquisition systems to overcome iron limitation in the presence of host erythrocytes.
Effective excitability captures network dynamics across development and phenotypes
2024-08-21

ABSTRACT Neuronal cultures in vitro are a versatile system for studying the fundamental properties of individual neurons and neuronal networks. Recently, this approach has gained attention as a precision medicine tool. Mature neuronal cultures in vitro exhibit synchronized collective dynamics called network bursting. If analyzed appropriately, this activity could offer insights into the network’s properties, such as its composition, topology, and developmental and pathological processes. A promising method for investigating the collective dynamics of neuronal networks is to map them onto simplified dynamical systems. This approach allows the study of dynamical regimes and the characteristics of the parameters that lead to data-consistent activity. We designed a simple biophysically inspired dynamical system and used Bayesian inference to fit it to a large number of recordings of in vitro population activity. Even with a small number of parameters, the model showed strong inter-parameter dependencies leading to invariant bursting dynamics for many parameter combinations. We further validated this observation in our analytical solution. We found that in vitro bursting can be well characterized by each of three dynamical regimes: oscillatory, bistable, and excitable. The probability of finding a data-consistent match in a particular regime changes with network composition and development. The more informative way to describe the in vitro network bursting is the effective excitability, which we analytically show to be related to the parameter-invariance of the model’s dynamics. We establish that the effective excitability can be estimated directly from the experimentally recorded data. Finally, we demonstrate that effective excitability reliably detects the differences between cultures of cortical, hippocampal, and human pluripotent stem cell-derived neurons, allowing us to map their developmental trajectories. Our results open a new avenue for the model-based description of in vitro network phenotypes emerging across different experimental conditions.
The HERMES (High Energy Rapid Modular Ensemble of Satellites) Pathfinder mission
2024-08-21

HERMES (High Energy Rapid Modular Ensemble of Satellites) Pathfinder is a\\nspace-borne mission based on a constellation of six nano-satellites flying in a\\nlow-Earth orbit (LEO). The 3U CubeSats, to be launched in early 2025, host\\nminiaturized instruments with a hybrid Silicon Drift Detector/GAGG:Ce\\nscintillator photodetector system, sensitive to X-rays and gamma-rays in a\\nlarge energy band. HERMES will operate in conjunction with Australian Space\\nIndustry Responsive Intelligent Thermal (SpIRIT) 6U CubeSat, launched in\\nDecember 2023. HERMES will probe the temporal emission of bright high-energy\\ntransients such as Gamma-Ray Bursts (GRBs), ensuring a fast transient\\nlocalization in a field of view of several steradians exploiting the\\ntriangulation technique. HERMES intrinsically modular transient monitoring\\nexperiment represents a keystone capability to complement the next generation\\nof gravitational wave experiments. In this paper we outline the scientific\\ncase, development and programmatic status of the mission\\n
Microchannel plate detectors for ultraviolet astronomy
2024-08-21

Beyond the lifetime of the Hubble Space Telescope, observational access to the ultraviolet (UV) might be quite limited. Therefore, small missions with short development times are required to bridge the gap to future larger missions in this important wavelength range. Even with the progress in adapting silicon sensors for the UV, single-photon-counting and visible-blind microchannel plate (MCP) detectors can provide a competitive signal-to-noise performance, particularly in the far- and extreme-UV, and enable simple instrument designs for small and cheap missions.<br /><br />Our MCP detector development aims at reaching enhanced sensitivity and increased lifetime with lower size, mass, and power consumption. Therefore, the design comprises (Al)GaN photocathodes with a tunable long-wavelength cut-off, long-life borosilicate MCPs, and a cross-strip anode with an FPGA-based readout.<br /><br />In this contribution, we report on the overall status of the detector development and give an outlook on the mission prospects.
The Wide Field Monitor (WFM) of the China-Europe eXTP (enhanced X-ray Timing and Polarimetry) mission
2024-08-21

The eXTP mission is a major project of the Chinese Academy of Sciences (CAS), with a large involvement of Europe. Its scientific payload includes four instruments: SFA, PFA, LAD and WFM. They offer an unprecedented simultaneous wide-band Xray timing and polarimetry sensitivity. A large European consortium is contributing to the eXTP study, both for the science and the instrumentation. Europe is expected to provide two of the four instruments: LAD and WFM; the LAD is led by Italy and the WFM by Spain. The WFM for eXTP is based on the design originally proposed for the LOFT ESA M3 mission, that underwent a Phase A feasibility study. It will be a wide field of view X-ray monitor instrument working in the 2-50 keV energy range, achieved with large-area Silicon Drift Detectors (SDDs), similar to the ones used for the LAD but with better spatial resolution. The WFM will consist of 3 pairs of coded mask cameras with a total combined field of view (FoV) of 90x180 degrees at zero response and a source localisation accuracy of ~1 arc min. The main goal of the WFM is to provide triggers for the target of opportunity observations of the SFA, PFA and LAD, in order to perform the core science programme, dedicated to the study of matter under extreme conditions of density, gravity and magnetism. In addition, the unprecedented combination of large field of view and imaging capability, down to 2 keV, of the WFM will allow eXTP to make important discoveries of the variable and transient X-ray sky, and provide X-ray coverage of a broad range of astrophysical objects covered under 'observatory science', such as gamma-ray bursts, fast radio bursts, gravitational wave electromagnetic counterparts. In this paper we provide an overview of the WFM instrument, explaining its design, configuration, and anticipated performance.
Deep inverse modeling reveals dynamic-dependent invariances in neural circuit mechanisms
2024-08-22

Neural population dynamics are shaped by many cellular, synaptic, and network properties. Not only is it important to understand how coordinated changes in circuit parameters alter neural activity, but also when dynamics are unaffected by—or invariant to—such changes. Computational modeling has revealed invariances in single neurons and small circuits that are thought to reflect their robustness against variability and perturbations. However, generalizing these insights to larger circuits in cortex and other brain areas remains challenging. A key bottleneck lies in inverse modeling of neural circuits with spiking network models, i.e., identifying parameter configurations that quantitatively match dynamics observed in neural recordings. Here, we present Automated Model Inference from Neural Dynamics (AutoMIND) for efficient discovery of invariant circuit model configurations. AutoMIND leverages a mechanistic model with adaptive spiking neurons and clustered connectivity, which displays a rich variety of spatiotemporal dynamics. Probabilistic deep generative models—trained on network simulations only—then returns many parameter configurations consistent with a given target observation of neural activity. Applied to several datasets, AutoMIND discovers circuit models of synchronous network bursting in human brain organoids across early development, as well as models capturing complex frequency profiles of Neuropixels recordings in mouse hippocampus and cortex. In each case, we obtain hundreds of configurations that compose a (nonlinear) parameter subspace in which population dynamics remain unchanged. Surprisingly, global and local geometries of the invariant subspace are not fixed, but differ for different dynamics. Together, our results shed light on dynamic-dependent invariances of circuit parameters underlying diverse population dynamics, while demonstrating the flexibility of AutoMIND for inverse modeling of neural circuits.
A Comparison of ChatGPT and Multidisciplinary Team Meeting Treatment Recommendations in 10 Consecutive Cervical Cancer Patients
2024-08-22

Background The preparation of multidisciplinary team (MDT) meetings can be time-consuming. In addition to the clinical data being available digitally in subsystems, the preparation of more complex cases requires literature research. Several expert systems have been developed to support this process. However, the interaction with these systems has to be trained. Current development enables linguistic interaction with such artificial intelligence (AI) systems. To the best of our knowledge, these have not been tested as premedical screening tools for MDT. Methods This is a retrospective consecutive case series of 10 cervical cancer cases comparing the medical recommendations of the MDT and artificial intelligence (AI) on a low level (i.e., surgery, systemic treatment, and radiotherapy). Results The clinical cases ranged from primary diagnosis via suspected recurrence to palliative settings. The AI repeatedly stated that medical professionals need to be consulted before treatment decisions. The AI answers ranged from no agreement to overachievement by mentioning treatment options for preexisting risk factors (such as obesity). In standard cases, the AI answer matched well with the expert recommendations. In some cases, the AI answers were contrary to our treatment recommendation. Conclusion The interaction with current language AIs is temptingly easy, and the replies are very understandable. Despite the AI warning regarding medical recommendations in the majority of our cases, there was a good match with the MDT recommendations. However, in some cases, the medical evidence behind the answers was missing or in the worst case fictional. In our case series, the AI did not meet the requirements to support a clinical MDT meeting by prescreening the therapeutic options. However, it did exceed the expectations regarding the risk factors of the patients.
Blood coagulation in Prediabetes clusters–impact on all-cause mortality in individuals undergoing coronary angiography
2024-08-22

Abstract Background Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. Methods Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. Results Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. Conclusions High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies. Graphical Abstract
A direct comparison of single grain and multi-grain aliquot luminescence dating of feldspars from colluvial deposits in KwaZulu-Natal, South Africa
2024-08-22

Abstract. The erosional landscape of the Jojosi Dongas in KwaZulu-Natal, South Africa, expose accretionary slope deposits that preserve important geological and archaeological information. This landscape has been occupied by modern humans during the stone age for many thousands of years as evidenced by the presence of numerous stone artefacts interbedded within at least three phases of gully cut-and-fill deposits. A contextualisation of the artefacts and their role for human evolution in southern Africa, as well as developing an understanding of the environmental conditions that shaped this inhabited landscape, is only possible by establishing a robust chronological framework. Here we use luminescence dating of feldspars to constrain the geochronological framework for the sequence of accretionary hillslope deposition at Jojosi at three sampling locations. Initial suspicion of poor bleaching led us to measure single grains of feldspar, which revealed low luminescence sensitivity of the individual grains and a variable proportion of grains in saturation. Summing the luminescence signal of individual grains and creating synthetic aliquots enabled us to study the effect of signal averaging on the luminescence sensitivity, signal saturation, and dose distributions. We then compare the results from individual grain measurements and synthetic aliquots to true multi-grain aliquots. To allow for a quantification of the results, we apply four different dose models to the distributions, including the Central Age Model, the Average Dose Model, BayLum, and a standardised growth curve (SGC) approach using an averaged Ln/Tn value interpolated onto the SGC. Doses calculated for the different samples range from ~80 Gy to ~800 Gy and contain up to 67 % saturated grains. We evaluate the performance of the different dose models over this large dose range, with samples close to the saturation level of feldspar luminescence. On average we find good agreement between the results obtained using the different dose models, but observe that samples with a large number of saturated grains impact the consistency of the result. Overall, all dose models and data sets give consistent results below a saturated grain threshold of ~15 %, corresponding to a dose of ~120 Gy in this study. Finally, we favoured BayLum for age calculations of the single grain and multi-grain aliquot data sets, representing the opportunity to refine the chronology by including stratigraphic information in the age calculations. We were able to establish a chronology for the three sampled sections within the Jojosi Dongas constraining erosional and depositional processes from ~100 ka to ~700 ka, and human occupation of the area in the early MIS 5 and late MIS 6.
Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy
2024-08-22

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state, ultimately shortening the period of neurogenesis. This study provides a mechanism for DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families.
Genome-wide association study of copy number variations in Parkinson’s disease
2024-08-22

Abstract Objective To investigate the impact of copy number variations (CNVs) on Parkinson’s disease (PD) pathogenesis using genome-wide data and explore their role in sporadic PD. Methods We analyzed CNV data from 11,035 PD patients (including 2,731 early-onset PD (EOPD)) and 8,901 controls from the COURAGE-PD consortium using a sliding window CNV-GWAS and genome-wide burden analysis. The independent dataset from the Global Parkinson Genetics Program (GP2) consisted of 23,089 cases and 18,824 controls were used to validate our initial findings. Results The exploratory dataset identifies multiple CNV regions associated with PD risk. The nominated CNV loci were not confirmed in an independent dataset, except that only a deletion in the PRKN gene, a well-established EOPD locus, remained genome-wide significant and robustly supported. CNV burden analysis showed a higher prevalence of CNVs in PD-related genes in patients compared to controls (OR=1.56 [1.18-2.09], p=0.0013), with PRKN showing the highest burden (OR=1.47 [1.10-1.98], p=0.026). Patients with CNVs in PRKN had an earlier disease onset. Burden analysis with controls and EOPD patients showed similar results. Interpretation The largest CNV-based GWAS on PD highlights both the promise and pitfalls of array-based CNV detection in PD and underscores the relevance of whole-genome sequencing approaches in resolving the role of CNV in PD. The array-based findings are prone towards false positive findings that might arise either from platform limitations and/or cohort biases. Future studies require improved genotyping resolution and rigorous cross-cohort validation to reliably assess CNV contributions to PD risk.
Constraining the Number Density of the Accretion Disk Wind in Hercules X-1 Using Its Ionization Response to X-Ray Pulsations
2024-08-22

Abstract X-ray binaries are known to launch powerful accretion disk winds that can have a significant impact on the binary systems and their surroundings. To quantify the impact and determine the launching mechanisms of these outflows, we need to measure the wind plasma number density, an important ingredient in the theoretical disk wind models. While X-ray spectroscopy is a crucial tool for understanding the wind properties, such as their velocity and ionization, in nearly all cases, we lack the signal-to-noise ratio to constrain the plasma number density, weakening the constraints on the outflow location and mass outflow rate. We present a new approach to determining this number density in the X-ray binary Hercules X-1, by measuring the speed of the wind ionization response to the time-variable illuminating continuum. Hercules X-1 is powered by a highly magnetized neutron star, pulsating with a period of 1.24 s. We show that the wind number density in Hercules X-1 is sufficiently high to respond to these pulsations by modeling the ionization response with the time-dependent photoionization model tpho . We then perform a pulse-resolved analysis of the best-quality XMM-Newton observation of Hercules X-1 and directly detect the wind response, confirming that the wind density is at least 10 12 cm −3 . Finally, we simulate XRISM observations of Hercules X-1 and show that they will allow us to accurately measure the number density at different locations within the outflow. With XRISM, we will rule out ∼3 orders of magnitude in density parameter space, constraining the wind mass outflow rate, energetics, and its launching mechanism.
Fungal community influences niche differences – implications for species coexistence
2024-08-22

<title>Abstract</title> Semi-arid ecosystems offer very limited resources to plants, but they are inhabited by incredibly diverse communities of winter annual plants. Ecological theory suggests that a high degree of specialization in resource use and in interactions among plants and soil fungi may explain the coexistence of ecologically similar species in such diverse communities. Species-specific variation in net outcome (positive vs negative) of plant-soil fungi interactions, may lead to variation in mean fitness differences thus increasing opportunities of coexistence. Few studies tested how resources (water and nutrients) in combination with soil fungi affect plants’ fundamental niche across life stages. We experimentally tested germination and fitness differences under different combinations of water, nutrients and soil fungi treatments, using six winter annual species with different degrees of mycorrhizal dependence. Germination success of four out of six species was reduced by the absence of soil fungi, and this response was more severe for obligate mycorrhizal species. Presence of soil fungi ameliorated the production of plant biomass especially under limited water or nutrients, corroborating findings that beneficial interactions with soil fungi alleviate abiotic stress. This response was strong in mycorrhizal dependent species, but highly variable among non-mycorrhizal species, likely due to species-specific outcomes of interactions among plants and pathogenic fungi. We suggest that absence of important symbionts may reduce germination and increase seed dormancy, thus favoring temporal niche partitioning among species, while the net outcomes of plant-soil fungi interactions may reduce mean fitness differences favoring coexistence via equalizing processes.
Supplementary material to "A direct comparison of single grain and multi-grain aliquot luminescence dating of feldspars from colluvial deposits in KwaZulu-Natal, South Africa"
2024-08-22

This supplementary material provides additional information on the performed luminescence measurements and respective results, as well as further insights into the determination of internal K content and the nature of the samples.The supplementary material is divided in two sections: (1) Sample characterisation and dose rate determination and (2) Protocol determination and equivalent dose measurements.