julilili42/papers huggingface dataset:
The Role of Effector-Specific Task Representations in Voluntary Task Switching
2023-01-13

There has been an increasing interest in uncovering the mechanisms underpinning how people decide which task to perform at a given time. Many studies suggest that task representations are crucial in guiding such voluntary task selection behavior, which is primarily reflected in a bias to select task repetitions over task switches. However, it is not yet clear whether the task-specific motor effectors are also a crucial component of task representations when deciding to switch tasks. Across three experiments using different voluntary task switching (VTS) procedures, we show that a greater overlap in task representations with a task-to-finger mapping than task-to-hand mapping increases participants' switching behavior (Exp. 1 and Exp. 2), but not when they were instructed to randomly select tasks (Exp. 3). Thus, task-specific stimulus-response associations can change the way people mentally represent tasks and influence switching behavior, suggesting that motor effectors should be considered as a component of task representations in biasing cognitive flexibility.
New Intermetalloid Ge9‐clusters with Copper and Gold: Filling Vacancies in the Cluster Chemistry of [Ge9(Hyp)3]− (Hyp=Si(SiMe3)3)
2023-01-13

Abstract We present a series of new intermetalloid clusters (R 3 P)CuGe 9( (Hyp) 3 , (R=Me, Et, iPr, nBu, tBu) (Hyp=Si(SiMe 3 ) 3 ) (R 3 P)AuGe 9 (Hyp) 3 MGe 9 (Hyp) 3 (R=Ph, Me; M=Au, Cu). In conjunction with already known clusters, these give new insights into the bonding situation of metal bridged Ge 9 clusters as well as a better understanding of the formation of these clusters. Additionally, the intermetalloid clusters with the smallest phosphine PMe 3 show new bonding motives.
PDE6D Mediates Trafficking of Prenylated Proteins NIM1K and UBL3 to Primary Cilia
2023-01-13

Mutations in PDE6D impair the function of its cognate protein, phosphodiesterase 6D (PDE6D), in prenylated protein trafficking towards the ciliary membrane, causing the human ciliopathy Joubert Syndrome (JBTS22) and retinal degeneration in mice. In this study, we purified the prenylated cargo of PDE6D by affinity proteomics to gain insight into PDE6D-associated disease mechanisms. By this approach, we have identified a specific set of PDE6D-interacting proteins that are involved in photoreceptor integrity, GTPase activity, nuclear import, or ubiquitination. Among these interacting proteins, we identified novel ciliary cargo proteins of PDE6D, including FAM219A, serine/threonine-protein kinase NIM1 (NIM1K), and ubiquitin-like protein 3 (UBL3). We show that NIM1K and UBL3 localize inside the cilium in a prenylation-dependent manner. Furthermore, UBL3 also localizes in vesicle-like structures around the base of the cilium. Through affinity proteomics of UBL3, we confirmed its strong interaction with PDE6D and its association with proteins that regulate small extracellular vesicles (sEVs) and ciliogenesis. Moreover, we show that UBL3 localizes in specific photoreceptor cilium compartments in a prenylation-dependent manner. Therefore, we propose that UBL3 may play a role in the sorting of proteins towards the photoreceptor outer segment, further explaining the development of PDE6D-associated retinal degeneration.
Limited Stability of 6,13-Bis(tri(isopropyl)silylethynyl)pentacene upon One-Electron Oxidation: Electrochemically Induced (4 + 2) Cycloaddition between an Alkynyl-Substituted Acene and Its Radical Cation
2023-01-13

6,13-Bis(tri(isopropyl)silylethynyl)pentacene, a particularly stable acene derivative important for (opto)electronic materials, turns reactive upon electrochemical one-electron oxidation. One of the typically stabilizing tri(isopropyl)silylethynyl substituents becomes involved in a (4 + 2) cycloaddition after redox umpolung. The electrosynthetic dimerization of the title compound provides easy access under mild conditions to a complex scaffold, which includes an intact pentacene, an anthracene, and a phenylene unit, all electronically separated. The product's electrochemical redox properties are explained by superimposed cyclic voltammetric features of the pentacene and the anthracene moieties. The reaction path is analyzed on the basis of electroanalytical and ESR data, and an oxidation-cycloaddition-reduction sequence is elaborated. The contribution of homogeneous electron transfers (electron transfer chain reaction) is negligible, in accordance with the relative formal redox potentials of the starting compound and the product. Quantum chemical calculations indicate that the central cycloaddition should be described as a two-step process with a distonic radical cation intermediate. We suggest an extended notation to define the contribution of the components with respect to electron count in the two-step cycloaddition, [3 + 1, 1 + 1].
Multiparametric senescent cell phenotyping reveals CD24 osteolineage cells as targets of senolytic therapy in the aged murine skeleton
2023-01-13

ABSTRACT Senescence drives organismal aging, yet the deep characterization of senescent cells in vivo remains incomplete. Here, we applied mass cytometry by time-of-flight (CyTOF) using carefully validated antibodies to analyze senescent cells at single-cell resolution. We used multiple criteria to identify senescent mesenchymal cells that were growth arrested and resistant to apoptosis (p16+/Ki67-/BCL-2+; “p16KB” cells). These cells were highly enriched for senescence-associated secretory phenotype (SASP) and DNA damage markers and were strongly associated with age. p16KB cell percentages were also increased in CD24+ osteolineage cells, which exhibited an inflammatory SASP in aged mice and were robustly cleared by both genetic and pharmacologic senolytic therapies. Following isolation, CD24+ skeletal cells exhibited growth arrest, SA-βgal positivity, and impaired osteogenesis in vitro . These studies thus provide a new approach using multiplexed protein profiling by CyTOF to define senescent mesenchymal cells in vivo and identify a highly inflammatory, senescent CD24+ osteolineage population cleared by senolytics.
Generation of an induced pluripotent stem cell (iPSC) line from a patient with GEFS+ carrying a STX1B (p.Lys45delinsArgMetCysIleGlu and p.Leu46Met) mutation
2023-01-13

The STX1B gene encodes the presynaptic protein syntaxin-1B, which plays a major role in regulating fusion of synaptic vesicles. Mutations in STX1B are known to cause epilepsy syndromes, such as genetic epilepsies with febrile seizures plus (GEFS+). Here, we reprogrammed skin fibroblasts from a female patient affected by GEFS+ to human induced pluripotent stem cells (iPSCs). The patient carries an InDel mutation (c.133_134insGGATGTGCATTG; p.Lys45delinsArgMetCysIleGlu and c.135_136AC > GA; p.Leu46Met), located in the regulatory H<sub>abc</sub>-domain of STX1B. Successful reprogramming of cells was confirmed by a normal karyotype, expression of several pluripotency markers and the potential to differentiate into all three germ layers.
Energy-dependent dielectric tensor axes in monoclinic α-3,4,9,10-perylene tetracarboxylic dianhydride
2023-01-13

We have determined the complex dielectric tensor of single crystalline 3,4,9,10-perylene tetracarboxylic&#13;\\ndianhydride (α-PTCDA) as a function of energy in the range between 1.4 and 5.0 eV. The results obtained&#13;\\nreflect the monoclinic symmetry of the crystal: The principal axes of the real and the imaginary part of the&#13;\\ntensor in general do not coincide and show chromatic dispersion. Monoclinic behavior allows rotation of the&#13;\\ncomponents εX and εZ in the plane perpendicular to the unique symmetry axis Y . The experimental results&#13;\\nindicate that the energies of the optical transitions observed in the weak εX component coincide with energies&#13;\\nin which a resonance effect due to coupling with the stronger εZ component occurs. These resonances appear&#13;\\nat energies close to electronic excitations such as the optical gap, the transport gap and the highest occupied&#13;\\nmolecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) peak-to-peak gap and their assignments&#13;\\nare discussed based on theoretical calculations
Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition inStaphylococcus aureus
2023-01-13

Abstract Sufficient access to transition metals such as iron is essential for bacterial proliferation and their active limitation within host tissues effectively restricts infection. To overcome iron limitation, the invasive pathogen Staphylococcus aureus uses the iron-regulated surface determinant (Isd) system to acquire hemoglobin-derived heme. While heme transport over the cell wall is well understood, its transport over the membrane is hardly investigated. In this study, we show the heme-specific permease IsdF to be energized by the general ATPase FhuC. Additionally, we show that IsdF needs appropriate location within the membrane for functionality. The membrane of S. aureus possesses special compartments (functional membrane microdomains – FMMs) to organize membrane complexes. We show IsdF to be associated with FMMs, to directly interact with the FMM scaffolding protein flotillin A (FloA) and to co-localize with the latter on intact bacterial cells. Additionally, Isd-dependent bacterial growth required FMMs and FloA. Our study shows that Isd-dependent heme acquisition requires a highly structured cell envelope to allow coordinated transport over the cell wall and membrane and it gives the first example of a bacterial nutrient acquisition system that depends on FMMs.
Fine-Tuning the Methodology of Sleep and Memory Research From a Human Behavioral Perspective
2023-01-13

Understanding the complex relationship between sleep and memory is a major challenge in neuroscience. Many studies on memory consolidation in humans suggest that sleep triggers offline memory processes, resulting in less forgetting of declarative memory and performance stabilization in non-declarative memory. However, an increasing number of contradictory findings reveal potential issues with how research is conducted in this field and call into question the reliability and interpretation of the results. All scientific disciplines face similar challenges. In this regard, research on the relationship between sleep and memory is still very fortunate. Yet, there is a constant need to fine-tune the methodology. In this article, we describe four behavioral methodological issues in human sleep and memory research that should be improved: non-optimal experimental designs, task complexity, fatigue effects in repetitive tasks, and inappropriate data analysis practices. We then offer solutions to each of these issues. We believe that implementing these solutions in future sleep and memory research will lead to more reliable results and significantly advance our understanding in this field.
TGF-Beta Modulates the Integrity of the Blood Brain Barrier In Vitro, and Is Associated with Metabolic Alterations in Pericytes
2023-01-14

The blood–brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintaining BBB integrity, can be functionally modified by GBM cells which induce proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors. We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as an in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, leading to the disruption of a so far intact and tight BBB. TGF-β notably changed the metabolic behavior of pericytes, by shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by modulating pathways that are necessary for the biosynthesis of molecules used for proliferation and cell division. Combined metabolomic and transcriptomic analyses further underscored that the observed functional and metabolic changes of TGF-β-treated pericytes are closely connected with their role as important supporting cells during angiogenic processes.
Interaction between nanomaterials and the innate immune system across evolution
2023-01-14

ABSTRACT Interaction of engineered nanomaterials (ENMs) with the immune system mainly occurs with cells and molecules of innate immunity, which are present in interface tissues of living organisms. Immuno‐nanotoxicological studies aim at understanding if and when such interaction is inconsequential or may cause irreparable damage. Since innate immunity is the first line of immune reactivity towards exogenous agents and is highly conserved throughout evolution, this review focuses on the major effector cells of innate immunity, the phagocytes, and their major sensing receptors, Toll‐like receptors (TLRs), for assessing the modes of successful versus pathological interaction between ENMs and host defences. By comparing the phagocyte‐ and TLR‐dependent responses to ENMs in plants, molluscs, annelids, crustaceans, echinoderms and mammals, we aim to highlight common recognition and elimination mechanisms and the general sufficiency of innate immunity for maintaining tissue integrity and homeostasis.
Quantitative Oculomotor Assessment in Hereditary Ataxia: Discriminatory Power, Correlation with Severity Measures, and Recommended Parameters for Specific Genotypes
2023-01-14

Abstract Characterizing bedside oculomotor deficits is a critical factor in defining the clinical presentation of hereditary ataxias. Quantitative assessments are increasingly available and have significant advantages, including comparability over time, reduced examiner dependency, and sensitivity to subtle changes. To delineate the potential of quantitative oculomotor assessments as digital-motor outcome measures for clinical trials in ataxia, we searched MEDLINE for articles reporting on quantitative eye movement recordings in genetically confirmed or suspected hereditary ataxias, asking which paradigms are most promising for capturing disease progression and treatment response. Eighty-nine manuscripts identified reported on 1541 patients, including spinocerebellar ataxias (SCA2, n = 421), SCA3 ( n = 268), SCA6 ( n = 117), other SCAs ( n = 97), Friedreich ataxia (FRDA, n = 178), Niemann-Pick disease type C (NPC, n = 57), and ataxia-telangiectasia ( n = 85) as largest cohorts. Whereas most studies reported discriminatory power of oculomotor assessments in diagnostics, few explored their value for monitoring genotype-specific disease progression ( n = 2; SCA2) or treatment response ( n = 8; SCA2, FRDA, NPC, ataxia-telangiectasia, episodic-ataxia 4). Oculomotor parameters correlated with disease severity measures including clinical scores ( n = 18 studies (SARA: n = 9)), chronological measures (e.g., age, disease duration, time-to-symptom onset; n = 17), genetic stratification ( n = 9), and imaging measures of atrophy ( n = 5). Recurrent correlations across many ataxias (SCA2/3/17, FRDA, NPC) suggest saccadic eye movements as potentially generic quantitative oculomotor outcome. Recommendation of other paradigms was limited by the scarcity of cross-validating correlations, except saccadic intrusions (FRDA), pursuit eye movements (SCA17), and quantitative head-impulse testing (SCA3/6). This work aids in understanding the current knowledge of quantitative oculomotor parameters in hereditary ataxias, and identifies gaps for validation as potential trial outcome measures in specific ataxia genotypes.
Nailfold capillaroscopy and deep learning in diabetes
2023-01-15

Abstract Objective To determine whether nailfold capillary images, acquired using video capillaroscopy, can provide diagnostic information about diabetes and its complications. Research Design and Methods Nailfold video capillaroscopy was performed in 120 adult patients with and without type 1 or type 2 diabetes, and with and without cardiovascular disease. Nailfold images were analyzed using convolutional neural networks, a deep learning technique. Cross‐validation was used to develop and test the ability of models to predict five5 prespecified states (diabetes, high glycosylated hemoglobin, cardiovascular event, retinopathy, albuminuria, and hypertension). The performance of each model for a particular state was assessed by estimating areas under the receiver operating characteristics curves (AUROC) and precision recall curves (AUPR). Results A total of 5236 nailfold images were acquired from 120 participants (mean 44 images per participant) and were all available for analysis. Models were able to accurately identify the presence of diabetes, with AUROC 0.84 (95% confidence interval [CI] 0.76, 0.91) and AUPR 0.84 (95% CI 0.78, 0.93), respectively. Models were also able to predict a history of cardiovascular events in patients with diabetes, with AUROC 0.65 (95% CI 0.51, 0.78) and AUPR 0.72 (95% CI 0.62, 0.88) respectively. Conclusions This proof‐of‐concept study demonstrates the potential of machine learning for identifying people with microvascular capillary changes from diabetes based on nailfold images, and for possibly identifying those most likely to have diabetes‐related complications.
Probing Bidirectional Plasmon‐Plasmon Coupling‐Induced Hot Charge Carriers in Dual Plasmonic Au/CuS Nanocrystals
2023-01-15

Abstract Heterostructured Au/CuS nanocrystals (NCs) exhibit localized surface plasmon resonance (LSPR) centered at two different wavelengths (551 and 1051 nm) with a slight broadening compared to respective homostructured Au and CuS NC spectra. By applying ultrafast transient absorption spectroscopy we show that a resonant excitation at the respective LSPR maxima of the heterostructured Au/CuS NCs leads to the characteristic hot charge carrier relaxation associated with both LSPRs in both cases. A comparison of the dual plasmonic heterostructure with a colloidal mixture of homostructured Au and CuS NCs shows that the coupled dual plasmonic interaction is only active in the heterostructured Au/CuS NCs. By investigating the charge carrier dynamics of the process, we find that the observed interaction is faster than phononic or thermal processes (&lt; 100 fs). The relaxation of the generated hot charge carriers is faster for heterostructured nanocrystals and indicates that the interaction occurs as an energy transfer (we propose Landau damping or interaction via LSPR beat oscillations as possible mechanisms) or charge carrier transfer between both materials. Our results strengthen the understanding of multiplasmonic interactions in heterostructured Au/CuS NCs and will significantly advance applications where these interactions are essential, such as catalytic reactions.
The patchwork loess of Central Asia: Implications for interpreting aeolian dynamics and past climate circulation in piedmont regions
2023-01-15

ABSTRACT Reconstruction of mass accumulation rates (MARs) in loess deposits are widely used for interpreting long‐term aeolian transport and climate dynamics in terrestrial environments. However, these interpretations are often driven by a preponderance of reconstructions from individual or selected sites, which can bias our understanding of past climate, especially in the absence of other proxy information. Recent studies on MARs from multiple loess sites in Arid Central Asia (ACA) reveal disparities in the timing of peaks in accumulation between sites, as well as asynchronies with loess flux in the Chinese Loess Plateau (CLP). We investigate this issue by (1) dating five new sites from the western Ili Basin, therefore extending the spatial cover of loess chronologies across ACA and (2) combining that with MARs from &gt;30 sites across ACA and the CLP over the last 60 ka. Our results indicate spatio‐temporal inhomogeneity in the timing and rate of loess deposition across the ACA, and highlight the importance of interrogating local and regional influences on dust supply and transport. Our synthesis of MARs from ACA and the CLP suggests that the timing of peak dust flux as an indicator of large‐scale climate dynamics is best derived from an aggregate of sites; this removes site‐specific bias where local processes or topographic settings outweigh the climate signature.
PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals
2023-01-16

In 2016 and 2018, Chung, Jansen and others described a new syndrome caused by haploinsufficiency of PHIP (pleckstrin homology domain interacting protein, OMIM *612,870) and mainly characterized by developmental delay (DD), learning difficulties/intellectual disability (ID), behavioral abnormalities, facial dysmorphism and obesity (CHUJANS, OMIM #617991). So far, PHIP alterations appear to be a rare cause of DD/ID. “Omics” technologies such as exome sequencing or array analyses have led to the identification of distinct types of alterations of PHIP , including, truncating variants, missense substitutions, splice variants and large deletions encompassing portions of the gene or the entire gene as well as adjacent genomic regions. We collected clinical and genetic data of 23 individuals with PHIP -associated Chung-Jansen syndrome (CHUJANS) from all over Europe. Follow-up investigations (e.g. Sanger sequencing, qPCR or Fluorescence-in-situ-Hybridization) and segregation analysis showed either de novo occurrence or inheritance from an also (mildly) affected parent. In accordance with previously described patients, almost all individuals reported here show developmental delay (22/23), learning disability or ID (22/23), behavioral abnormalities (20/23), weight problems (13/23) and characteristic craniofacial features (i.e. large ears/earlobes, prominent eyebrows, anteverted nares and long philtrum (23/23)). To further investigate the facial gestalt of individuals with CHUJANS, we performed facial analysis using the GestaltMatcher approach. By this, we could establish that PHIP patients are indistinguishable based on the type of PHIP alteration (e.g. missense, loss-of-function, splice site) but show a significant difference to the average face of healthy individuals as well as to individuals with Prader-Willi syndrome (PWS, OMIM #176270) or with a CUL4B -alteration (Intellectual developmental disorder, X-linked, syndromic, Cabezas type, OMIM #300354). Our findings expand the mutational and clinical spectrum of CHUJANS. We discuss the molecular and clinical features in comparison to the published individuals. The fact that some variants were inherited from a mildly affected parent further illustrates the variability of the associated phenotype and outlines the importance of a thorough clinical evaluation combined with genetic analyses for accurate diagnosis and counselling.