julilili42/papers huggingface dataset:
Discarded sequencing reads uncover natural variation in pest resistance in Thlaspi arvense
2024-12-19

Understanding the genomic basis of natural variation in plant pest resistance is an important goal in plant science, but it usually requires large and labor-intensive phenotyping experiments. Here, we explored the possibility that non-target reads from plant DNA sequencing can serve as phenotyping proxies for addressing such questions. We used data from a whole-genome and -epigenome sequencing study of 207 natural lines of field pennycress ( Thlaspi arvense ) that were grown in a common environment and spontaneously colonized by aphids, mildew, and other microbes. We found that the numbers of non-target reads assigned to the pest species differed between populations, had significant SNP-based heritability, and were associated with climate of origin and baseline glucosinolate contents. Specifically, pennycress lines from cold and thermally fluctuating habitats, presumably less favorable to aphids, showed higher aphid DNA load, i.e., decreased aphid resistance. Genome-wide association analyses identified genetic variants at known defense genes but also novel genomic regions associated with variation in aphid and mildew DNA load. Moreover, we found several differentially methylated regions associated with pathogen loads, in particular differential methylation at transposons and hypomethylation in the promoter of a gene involved in stomatal closure, likely induced by pathogens. Our study provides first insights into the defense mechanisms of Thlaspi arvense , a rising crop and model species, and demonstrates that non-target whole-genome sequencing reads, usually discarded, can be leveraged to estimate intensities of plant biotic interactions. With rapidly increasing numbers of large sequencing datasets worldwide, this approach should have broad application in fundamental and applied research.
Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase-dependent mechanism
2024-12-19

The Parkinson’s disease (PD)-linked protein Leucine-Rich Repeat Kinase 2 (LRRK2) consists of seven domains, including a kinase and a Roc G domain. Despite the availability of several high-resolution structures, the dynamic regulation of its unique intramolecular domain stack is nevertheless still not well understood. By in-depth biochemical analysis, assessing the Michaelis–Menten kinetics of the Roc G domain, we have confirmed that LRRK2 has, similar to other Roco protein family members, a K M value of LRRK2 that lies within the range of the physiological GTP concentrations within the cell. Furthermore, the R1441G PD variant located within a mutational hotspot in the Roc domain showed an increased catalytic efficiency. In contrast, the most common PD variant G2019S, located in the kinase domain, showed an increased K M and reduced catalytic efficiency, suggesting a negative feedback mechanism from the kinase domain to the G domain. Autophosphorylation of the G1+2 residue (T1343) in the Roc P-loop motif is critical for this phosphoregulation of both the K M and the k cat values of the Roc-catalyzed GTP hydrolysis, most likely by changing the monomer–dimer equilibrium. The LRRK2 T1343A variant has a similar increased kinase activity in cells compared to G2019S and the double mutant T1343A/G2019S has no further increased activity, suggesting that T1343 is crucial for the negative feedback in the LRRK2 signaling cascade. Together, our data reveal a novel intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase-dependent mechanism. Interestingly, PD mutants differently change the kinetics of the GTPase cycle, which might in part explain the difference in penetrance of these mutations in PD patients.
Immersive Cave Environments in VR: A Tool for Exploring Altered States of Consciousness and Creativity in Archaeology
2024-12-19

This study explores the use of immersive Virtual Reality (VR) cave environments to investigate hypotheses concerning altered states of consciousness, creativity, and flexible thinking in archaeological contexts. Building on the premise that ancient humans used caves as sites for rituals involving altered consciousness, we recreated a virtual cave environment to simulate these experiences and examine their impact on participants’ cognitive processes. Participants engaged in pareidolic tasks within both a virtual cave and a virtual open-space environment, allowing for comparative analysis of semantic network organization and subjective experiences. Our findings show that the cave environment elicited higher emotional arousal and spiritual engagement, as well as an improvement in the aspects of creativity and flexible thinking. These results suggest that VR can serve as a powerful tool in archaeology for reconstructing early humans’ experiences and investigating their psychological and cognitive states, thus providing new insights into their use of caves for mind-altering or ritualistic purposes. This interdisciplinary approach contributes to both cognitive archaeology and the development of immersive VR technologies in scientific research.
Platelet spleen tyrosine kinase is a key regulator of anti-PF4 antibody–induced immunothrombosis
2024-12-20

Abstract Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but serious prothrombotic adverse event after vaccination with adenovector-based COVID-19 vaccines. Laboratory findings indicate that anti–platelet factor 4 (PF4) immunoglobulin G antibodies are the causing factor for the onset of thromboembolic events in VITT. However, molecular mechanisms of cellular interactions, signaling pathways and involvement of different cell types in VITT antibody–mediated thrombosis are not fully understood. Moreover, uncertainty exists regarding current treatment protocols because the sole anticoagulation was shown to be inefficient to prevent thrombosis progression in severe VITT cases. In this study, we demonstrate that platelet spleen tyrosine kinase (SYK) modulates anti-PF4 VITT-mediated thrombus formation in an ex vivo model of immunothrombosis. Our study showed that the selective inhibition of SYK can abrogate VITT antibody–driven procoagulant platelet formation, activation of plasmatic coagulation as well as platelet-leukocyte interplay. Most importantly, the specific inhibition of SYK in platelets but not in neutrophils prevented VITT antibody–induced multicellular thrombus formation, without perturbing the platelet function. Our findings indicate that the specific targeting of platelet SYK might be a promising therapeutic approach to prevent thrombotic complications in patients with antibody-mediated immunothrombosis.
A spatiotemporal style transfer algorithm for dynamic visual stimulus generation
2024-12-20

Abstract Understanding how visual information is encoded in biological and artificial systems often requires the generation of appropriate stimuli to test specific hypotheses, but available methods for video generation are scarce. Here we introduce the spatiotemporal style transfer (STST) algorithm, a dynamic visual stimulus generation framework that allows the manipulation and synthesis of video stimuli for vision research. We show how stimuli can be generated that match the low-level spatiotemporal features of their natural counterparts, but lack their high-level semantic features, providing a useful tool to study object recognition. We used these stimuli to probe PredNet, a predictive coding deep network, and found that its next-frame predictions were not disrupted by the omission of high-level information, with human observers also confirming the preservation of low-level features and lack of high-level information in the generated stimuli. We also introduce a procedure for the independent spatiotemporal factorization of dynamic stimuli. Testing such factorized stimuli on humans and deep vision models suggests a spatial bias in how humans and deep vision models encode dynamic visual information. These results showcase potential applications of the STST algorithm as a versatile tool for dynamic stimulus generation in vision science.
Willingness to protect bird species depends on individual respondents' demographic and species traits
2024-12-20

Abstract Willingness to donate and to protect (WTP) is an important part of worldwide nature conservation, and animals can be used as flagships for establishing conservation measures and collecting donations. We here focus on 141 German bird species to address factors that impact WTP by using a survey on the individual respondent level. Further, another analysis assessed traits on the species level. A total of 1003 respondents participated in the survey. Results of an analysis of covariance suggest that, at the level of the individual, subjective cuteness rating, coloration, species knowledge, and age positively influenced WTP. On the species trait level based on the 141 species, cuteness, coloration, and internet salience were positively related to WTP, and presence at feeders, eBird entries, and global abundance were negatively related to WTP. This is one of the first studies based on a large number of bird species from Europe and it can inform regional nongovernmental organizations for selecting charismatic species for conservation communications. Moreover, this study consequently addresses cuteness in birds as an important factor.
Youth cultural practices as modes of time work: Chilling as rescheduling everyday life
2024-12-20

The phenomenon of young people reclaiming their time by rejecting traditional expectations associated with specific roles and engaging in activities that are socially addressed to be devoid of purpose, such as hanging out and chilling , is complex and multifaceted. It encompasses a range of meanings and is not simply what others call a waste of time. While many adults consider this phenomenon as wasting time by “doing nothing” or something that can be done after fulfilling the student role, young people employ these terms to refer to activities such as socializing, engaging in leisure, or taking me time. In Germany, young people have increasingly referred to hanging out as chilling in recent decades. This paper starts from the assumption that social acceleration, including temporalization of time and daily life to ensure social synchronization and coordinated actions, is an important trend in contemporary societies. Against this background, the article aims to ascertain the extent to which chilling represents a youth cultural expression of “time work” insofar as young people demonstrate the agency to negotiate the complexities of life, particularly in how they perceive and interpret time, simply by chilling. The concept of time work offers a crucial lens for understanding the temporal experiences connected to chilling, particularly in relation to how young people grow up and navigate life's uncertainties. Thus, rather than a moment of doing nothing, this article contends that chilling is a central temporal experience during the youth phase as a form of “time work.” Accordingly, chilling should be seen as a youth cultural response to the decelerating demands of the youth phase; it offers the means by which young people regain structural control over their biographical time with peers.
Interpreting cooling dates and histories from laser ablation in situ (U–Th–Sm) ∕ He thermochronometry: a modelling perspective
2024-12-20

Abstract. Recent applications of the in situ (U–Th–Sm) / He thermochronometry technique demonstrate its potential to address some of the analytical challenges associated with the whole-grain technique. In this study, we adapted state-of-the-art apatite and zircon production–ejection–diffusion models for application to in situ dating methods, aiming to enhance the applicability of this technique to a broad range of geologic samples and applications. Our modifications to thermal history models include accommodation of the full range of stopping distances for alpha particles and cylindrical grain geometries. This investigation focuses on several key aspects of in situ data interpretation: (i) exploring the relationship between in situ dates and the position of ablation spots across individual grains, (ii) assessing differences and similarities between whole-grain and in situ dates, (iii) determining optimal strategies and performance for reconstructing cooling histories from in situ (U–Th–Sm) / He data, and (iv) reporting the effects of radionuclide zoning on (U–Th–Sm) / He thermochronology. Results indicate that the measured in situ helium distribution is a function of grain size, ablation spot position and size, and cooling history. Together, these analytical and natural factors result in systematic variations in in situ dates with distance from the grain rim. Therefore, similar to whole-grain analyses, robust interpretation requires determining grain geometry and the distance of the laser spot from the nearest prismatic face. In most cases, resulting in situ dates are approximately 30 % older than corresponding alpha-ejection-corrected whole-grain dates, irrespective of the cooling rate and grain size. Whole-grain and in situ dates are similar solely for gem-sized samples or samples exhibiting negligible diffusional helium loss and thus spent more time at surface temperatures compared to their transit time through the partial retention zone. Reconstruction of cooling histories using in situ (U–Th–Sm) / He data can be achieved through single measurements in several grains with varying grain size and/or effective uranium content or within a single grain with measurements taken at different distances from the grain rim. In addition, statistical analysis of a large compilation of measured radionuclide variations in apatite and zircon grains reveals that radionuclide zoning strongly impacts whole-grain analyses but can be directly measured with the in situ method. Overall, our results suggest that in situ measurements for (U–Th–Sm) / He date determination offer a means to extract meaningful cooling signals from samples with poor reproducibility from traditional whole-grain techniques.
Persistent Epstein–Barr Virus Infection of Epithelial Cells Leads to APOBEC3C Expression and Induces Mitochondrial DNA Mutations
2024-12-20

ABSTRACT Upon infection with the virus, cells increase the expression of cytidine deaminase APOBEC3 family genes. This leads to the accumulation of C‐to‐T mutations in the replicating viral genome and suppresses viral propagation. In contrast, herpesviruses, including Epstein–Barr virus (EBV), express genes that counteract APOBEC3 during lytic infection. However, because viral resistance factors are not expressed during EBV latent infection, it is unknown how APOBEC3 functions during latent infection. We observed that in gastric epithelial cells persistently infected with EBV, the expression of APOBEC3 family genes increased, C‐to‐T mutations in the D‐loop genome of mitochondrial DNA (mtDNA) increased, and mtDNA copy number decreased. By introducing and expressing individual APOBEC3 family genes, APOBEC3C was particularly expressed in the cytoplasm, increasing C‐to‐T mutations in mtDNA and decreasing mtDNA copy number. Furthermore, we confirmed that APOBEC3C co‐localized with mitochondria in EBV‐infected cells. Expression of the EBV latent gene LMP2A increased APOBEC3C expression. Conversely, APOBEC3C expression was reduced in LMP2A‐deficient EBV‐infected cells compared to wild‐type EBV‐infected cells. These results indicate that persistent infection of EBV in gastric epithelial cells reduces the number of mitochondria through mtDNA mutations induced by APOBEC3C expression.
Plasma zinc and selenium levels in adult inpatients with Lassa fever in Nigeria: A case-controlled study
2024-12-20

Significantly low levels of zinc and selenium were observed in patients with LF compared with healthy controls, suggesting a role in susceptibility and pathogenesis. Given that zinc and selenium are essential trace elements for optimal functioning of the immune system, they may play a role in improving management outcomes.
Monitoring Shear-Zone Weakening in East Antarctic Outlet Glaciers through Differential InSAR Measurements
2024-12-20

Abstract. The stability of the Antarctic Ice Sheet depends on ice flux into the ocean through major outlet glaciers, which is resisted by shear stresses in the lateral shear margins both on grounded ice and on floating ice shelves. Within the tidal flexure zone, where the ice sheet transitions from fully grounded to freely-floating, ocean tides lead to a characteristic flexural pattern which can be detected by radar satellites in differential interferograms. Here, we investigate how spatially heterogeneous, elastic ice-shelf properties in the shear zones affect tidal flexure and if a corresponding signature can be detected in satellite observations. We use the Young’s modulus (which among others depends on ice temperature and/or ice crystal orientation fabric) as a bulk tuning variable for changing ice stiffness across shear zones and show that this leads to cm-scale deviations in vertical displacement compared to a homogeneous elastic flexure model. Using the tidal-flexure zone of Priestley Glacier as an example, we compare homogenous and heterogenous flexure-model predictions with observations from 31 differential interferograms. After adjusting the local tide model and validating it with in-situ GPS data, we find that a five-fold reduction of the Young’s modulus in the shear zone, i.e. an effective shear-zone weakening, reduces the root-mean-square-error of predicted and observed vertical displacement by 84 %, from 0.182 m to 0.03 m. This suggests that satellite interferometry can detect changing ice stiffness across shear zones with potential to inform ice-flow models about the often unknown spatial variability in ice-shelf properties along the grounding zone.
Novel Digital Anomalies, Hippocampal Atrophy, and Mutations Expand the Genotypic and Phenotypic Spectra of CNKSR2 in the Houge Type of X‐Linked Syndromic Intellectual Development Disorder (MRXSHG)
2024-12-20

ABSTRACT The Houge type of X‐linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2 , a gene located at Xp22.12. CNKSR2, also known as CNK2 or MAGUIN, functions as a synaptic scaffolding molecule within the neuronal postsynaptic density (PSD) of the central nervous system. It acts as a link connecting postsynaptic structural proteins, such as PSD95 and S‐SCAM, by employing multiple functional domains crucial for synaptic signaling and protein–protein interactions. Predominantly expressed in dendrites, CNKSR2 is vital for dendritic spine morphogenesis in hippocampal neurons. Its loss‐of‐function variants result in reduced PSD size and impaired hippocampal development, affecting processes including neuronal proliferation, migration, and synaptogenesis. We present 15 patients including three from the MENA (Middle East and North Africa), a region with no documented mutations in CNKSR2 . Each individual displays unique clinical presentations that encompass developmental delay, ID, language/speech delay, epilepsy, and autism. Genetic analyses revealed 14 distinct variants in CNKSR2 , comprising five nonsense, three frameshift, two splice, and four missense variants, of which 13 are novel. The ACMG guidelines unanimously interpreted these 14 variants in 15 individuals as pathogenic, highlighting the detrimental impact of these CNKSR2 genetic alterations and confirming the molecular diagnosis of MRXSHG. Importantly, variants Ser767Phe and Ala827Pro may lead to proteasomal degradation or reduced PSD size, contributing to the neurodevelopmental phenotype. Furthermore, these two amino acids, along with another two affected by four missense variants, exhibit complete conservation in nine vertebrate species, illuminating their crucial role in the gene's functionality. Our study revealed unique new digital and brain phenotype, including pointed fingertips (fetal pads of fingertips), syndactyly, tapering fingers, and hippocampal atrophy. These novel clinical features in MRXSHG, combined with 13 novel variants, expand the phenotypic and genotypic spectra of MRXSHG associated with CNKSR2 mutations.
Immune Cell Distributions in the Blood of Healthy Individuals at High Genetic Risk of Parkinson’s Disease
2024-12-20

The immune system likely plays a key role in Parkinson’s disease (PD) pathophysiology. Thus, we investigated whether immune cell compositions are already altered in healthy individuals at high genetic risk for PD. We quantified 92 immune cell subtypes in the blood of 442 individuals using multicolor flow cytometry. Polygenic risk scores (PGS) for PD were calculated based on genome-wide significant SNPs (n = 87) from a large genome-wide association study (n = 1,530,403). Linear regression analyses did not reveal significant associations between PGS and any immune cell subtype (FDR = 0.05). Nominally significant associations were observed for NKG2C+ B cells (p = 0.026) in the overall sample. Older participants at increased genetic PD risk also showed a higher proportion of myeloid dendritic cells (p = 0.019) and CD27+CD4+ memory T cells (p = 0.043). Several immune cells were nominally statistically associated in women only. These findings suggest that major alterations of immune cells only occur later in the progression of PD.
Comprehensive Analysis of Human Dendritic Spine Morphology and Density: Exploring Diversity of Human Dendritic Spines
2024-12-20

Abstract Dendritic spines, small protrusions on neuronal dendrites, play a crucial role in brain function by changing shape and size in response to neural activity. So far, in depth analysis of dendritic spines in human brain tissue is lacking. This study presents a comprehensive analysis of human dendritic spine morphology and density using a unique dataset from human brain tissue from 27 patients (8 females, 19 males, aged 18-71) undergoing tumor or epilepsy surgery at three neurosurgery sites. We used acute slices and organotypic brain slice cultures to examine dendritic spines, classifying them into the three main morphological subtypes: Mushroom, Thin, and Stubby, via 3D reconstruction using ZEISS arivis Pro software. A deep learning model, trained on 39 diverse datasets, automated spine segmentation and 3D reconstruction, achieving a 74% F1-score and reducing processing time by over 50%. We show significant differences in spine density by sex, dendrite type, and tissue condition. Females had higher spine densities than males, and apical dendrites were denser in spines than basal ones. Acute tissue showed higher spine densities compared to cultured human brain tissue. With time in culture, Mushroom spines decreased, while Stubby and Thin spine percentages increased, particularly from 7-9 to 14 days in vitro , reflecting potential synaptic plasticity changes. Our study underscores the importance of using human brain tissue to understand unique synaptic properties and shows that integrating deep learning with traditional methods enables efficient large-scale analysis, revealing key insights into sex- and tissue-specific dendritic spine dynamics relevant to neurological diseases. New and Noteworthy This study presents a dataset of nearly 4,000 morphologically reconstructed human dendritic spines across different ages, gender, and tissue conditions. The dataset was further used to evaluate a deep learning algorithm for three-dimensional spine reconstruction, offering a scalable method for semi-automated spine analysis across various tissues and microscopy setups. The findings enhance understanding of human neurology, indicating potential connections between spine morphology, brain function, and the mechanisms of neurological and psychiatric diseases.