julilili42/papers huggingface dataset:
The mitochondrial surface receptor Tom70 protects the cytosol against mitoprotein-induced stress
2020-09-15

Summary Most mitochondrial proteins are synthesized as precursors in the cytosol and post-translationally transported into mitochondria. The mitochondrial surface protein Tom70 acts at the interface of the cytosol and mitochondria. In vitro import experiments identified Tom70 as targeting receptor, particularly for hydrophobic carriers. Using in vivo methods and high content screens, we revisited the question of Tom70 function and considerably expanded the set of Tom70-dependent mitochondrial proteins. We demonstrate that the crucial activity of Tom70 is its ability to recruit cytosolic chaperones to the outer membrane. Indeed, tethering an unrelated chaperone-binding domain onto the mitochondrial surface complements most of the defects caused by Tom70 deletion. Tom70-mediated chaperone recruitment reduces the proteotoxicity of mitochondrial precursor proteins, in particular of hydrophobic inner membrane proteins. Thus, our work suggests that the predominant function of Tom70 is to tether cytosolic chaperones to the outer mitochondrial membrane, rather than to serve as a mitochondria-specifying targeting receptor.
On the interference from agar in chemical exchange saturation transfer MRI parameter optimization in model solutions
2020-09-15

Chemical exchange saturation transfer (CEST) MRI is currently set to become part of clinical routine as it enables indirect detection of low concentrated molecules and proteins. Recently, intermediate to fast exchanging functional groups of glucose and its derivatives, glutamate and dextran, have gained attention as promising CEST contrast agents. To increase the specificity of CEST MRI for certain functional groups, the presaturation module is commonly optimized. At an early stage, this is performed in well‐defined model solutions, in which, for instance, the relaxation times are adjusted to mimic in vivo conditions. This often involves agar, assuming the substance would not yield significant CEST effects by itself, which the current study proves to be an invalid assumption. Model solutions at different pH values and concentrations of agar were investigated at different temperatures at a 9.4 T human whole body MR scanner. High power presaturation of around 4 μT, optimal for investigating intermediate to fast exchanging groups, was applied. Postprocessing included spatiotemporal corrections for B 0 and spatial corrections for B 1 + . CEST effects of up to 3 % of the bulk water signal were observed. From pH, concentration and temperature dependency, it was concluded that the observed behavior reflects a CEST effect of agar. It was also shown how to remove this undesirable contribution from CEST MRI data. It was concluded that if agar is involved in the CEST MRI parameter optimization process, its contribution to the observed effects has to be taken into account. CEST agent concentration must be sufficiently high to be able to neglect the contribution of agar, or a control sample at matched pH is necessary for correction. Experiments on pure agarose showed reduced CEST effects compared with agar but did not provide a neutral baseline either.
Multidimensionality of gender ideology and relationships with gendered practices: an exploratory analysis across Europe in 2002 and 2012
2020-09-15

Many researchers assume a one-dimensionality of gender ideology constructs and/or stability of dimensions across countries and time, yet these assumptions have rarely been tested. WE apply factor analyses on two waves of the International Social Survey Programme in 2002 and 2012, and comparable European countries to test this. Our results show that gender ideologies can be distinguished into distinctive domains that relate to mother’s employment, women’s work, men’s role in the family, and finally women’s breadwinning. These dimensions have be found to be relatively stable across countries and time. Results from regression models investigating different aspects of the gender division of labour suggest that distinguishing dimensions is less important when considering gender ideologies at the individual level but can make a big difference when examining gender culture at the country level.
The Neural Bases of Tinnitus: Lessons from Deafness and Cochlear Implants
2020-09-16

Subjective tinnitus is the conscious perception of sound in the absence of any acoustic source. The literature suggests various tinnitus mechanisms, most of which invoke changes in spontaneous firing rates of central auditory neurons resulting from modification of neural gain. Here, we present an alternative model based on evidence that tinnitus is: (1) rare in people who are congenitally deaf, (2) common in people with acquired deafness, and (3) potentially suppressed by active cochlear implants used for hearing restoration. We propose that tinnitus can only develop after fast auditory fiber activity has stimulated the synapse formation between fast-spiking parvalbumin positive (PV<sup>+</sup>) interneurons and projecting neurons in the ascending auditory path and coactivated frontostriatal networks after hearing onset. Thereafter, fast auditory fiber activity promotes feedforward and feedback inhibition mediated by PV<sup>+</sup> interneuron activity in auditory-specific circuits. This inhibitory network enables enhanced stimulus resolution, attention-driven contrast improvement, and augmentation of auditory responses in central auditory pathways (neural gain) after damage of slow auditory fibers. When fast auditory fiber activity is lost, tonic PV<sup>+</sup> interneuron activity is diminished, resulting in the prolonged response latencies, sudden hyperexcitability, enhanced cortical synchrony, elevated spontaneous γ oscillations, and impaired attention/stress-control that have been described in previous tinnitus models. Moreover, because fast processing is gained through sensory experience, tinnitus would not exist in congenital deafness. Electrical cochlear stimulation may have the potential to reestablish tonic inhibitory networks and thus suppress tinnitus. The proposed framework unites many ideas of tinnitus pathophysiology and may catalyze cooperative efforts to develop tinnitus therapies.
Defibrotide for the Treatment of Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in 2 Pediatric Patients
2020-09-16

Abstract The pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 infection is a severe complication of coronavirus disease 2019. Since impaired coagulation and thrombosis/endotheliitis are suspected pathomechanisms, we treated 2 patients with defibrotide, a profibrinolytic, antithrombotic, antiinflammatory oligonucleotide. Symptoms resolved during treatment. Moreover, coagulation parameters indicating hypofibrinolysis and complement activation normalized. The pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 infection is a severe complication of coronavirus disease 2019. Since impaired coagulation and thrombosis/endotheliitis are suspected pathomechanisms, 2 patients received defibrotide, a profibrinolytic, antithrombotic, antiinflammatory oligonucleotide. Symptoms resolved and hypofibrinolysis/complement activation normalized during treatment.
Light‐Controlled Near‐Field Energy Transfer in Plasmonic Metasurface Coupled MoS2Monolayer
2020-09-16

Abstract The energy transfer from plasmonic nanostructures to semiconductors has been extensively studied to enhance light‐harvesting and tailor light–matter interactions. In this study, the efficient energy transfer from an Au metasurface to monolayered MoS 2 within a near‐field coupling regime is reported. The metasurface is designed and fabricated to demonstrate strong photoluminescence (PL) and cathodoluminescence (CL) emission spectra. In the coupled heterostructure of MoS 2 with a metasurface, both the Raman shift and absorption spectral intensities of monolayered MoS 2 are affected. The spectral profile and PL peak position can be tailored owing to the energy transfer between plasmonic nanostructures and semiconductors. This is confirmed by ultrafast lifetime measurement. A theoretical model of two coupled oscillators is proposed, where the expanded general solutions (EGS) of such a model result in a series of eigenvalues that correspond to the renormalization of energy levels in modulated MoS 2 . The model can predict the peak shift up to tens of nanometers in hybrid structures and hence provides an alternative method to describe energy transfer between metallic structures and two‐dimensional (2D) semiconductors. A viable approach for studying light–matter interactions in 2D semiconductors via near‐field energy transfer is presented, which may stimulate the applications of functional nanophotonic devices.
Gold‐Loaded Mesoporous Organosilica‐Silica Core‐Shell Nanoparticles as Catalytic Nanoreactors
2020-09-16

Despite immense research efforts in the field of noble metal‐loaded mesoporous silica nanoparticles, the rational design and fabrication of nanosystems with high catalytic efficiency are still a major challenge. The main obstacles are faced when adjusting the size of the implemented metal nanoparticles and when modulating the porosity of nanoreactor arrays. Herein, a series of hierarchically structured core‐shell nanoparticles was synthesized, consisting of a mesoporous siliceous shell and either a thiol‐functionalized mesoporous organosilica core (SH‐MON‐n@MS; n = 1, 2, 3, 4) or an amino‐functionalized variant (NH 2 ‐MON@MS). The distinct core/shell composition enables a selective loading of Au nanoparticles into the core domain affording the hierarchically structured materials Au/SH‐MON‐n@MS (n = 1, 2, 3, 4) and Au/NH 2 ‐MON@MS. The larger shell mesopores facilitate easy access and diffusion of reactants and products, while the inner organosilica pores provide a hydrophobic microenvironment. Due to the superior structural properties, the materials Au/SH‐MON‐n@MS (n = 1, 2, 3, 4) exhibit excellent catalytic performance in the reduction of 4‐nitrophenol to 4‐aminophenol. However, the aerobic oxidation of benzyl alcohol to benzaldehyde is only promoted by Au/SH‐MON‐2@MS, revealing that Au loading and the core pores are main factors to govern the catalytic performance, while the air‐flow rate takes also a key role in the catalytic conversion.
The Differences and Similarities between Curiosity and Interest: Meta-analysis and Network Analyses
2020-09-16

The relationship and difference between curiosity and interest have received considerable attention and discussion. Yet, most of the discussions have not been based on empirical evidence. Here we report three studies examining the relationship between curiosity and interest. The first study was a meta-analysis that examined the Pearson correlations between scales assessing curiosity and interest. Based on 24 studies (31 effect sizes), we found that the curiosity scales correlated with the interest scales at a moderate level (r = .53), but they had extremely high heterogeneity, suggesting that the relationship largely depended on how they were conceptualized. The second and third studies applied network analyses (i.e., co-occurrence analysis and correlation-based analysis) to data that was collected using experience sampling method, examining the way in which the subjective feelings of curiosity and interest are related. Across the studies, we found consistent differences between the feelings associated with curiosity and those associated with interest. While the feelings of curiosity reflected feelings of inquisitiveness and eagerness to know more, the feelings of interest were aligned with positive affect such as enjoyment and happiness. Importantly, an asymmetrical pattern was found in curiosity-interest co-occurrences: when the feelings of curiosity occurred, the co-occurrence of the feelings of interest was highly likely, but not so vice versa. That is, when the feelings of interest occurred, the feelings of curiosity did not always co-occur. Theoretical and practical implications of these findings are discussed.
Influence of 99m-Tc-Nanocolloid Activity Concentration on Sentinel Lymph Node Detection in Endometrial Cancer: A Quantitative SPECT/CT Study
2020-09-16

This study evaluates quantitative combined single photon emission tomography/computed x-ray tomography (SPECT/CT) to assess the influence of radiotracer concentration on detection of sentinel lymph nodes (SLN) in endometrial cancer (EC). Eighty EC patients underwent pericervical 99m-Tc-nanocolloid injection followed by SPECT/CT. The subgroup of patients with failed SLN detection in SPECT/CT (n = 20) was compared to match-paired patients showing at least two SLNs. Results of intraoperative gamma probe measurements and quantitative SPECT/CT were used for comparison. In patients with detection failure, the percentage of injected dose, absolute activity, and volume of the injection site were significantly lower (30 ± 24% vs. 55 ± 19%; p = 0.01, 43 ± 36 MBq vs. 73 ± 33 MBq; p = 0.04, and 183 ± 164 mL vs. 266 ± 164 mL; p = 0.03) while mean activity concentration in liver, spleen, and bone marrow was significantly higher (p = 0.02). Activity concentration (&gt;33 KBq/mL) and absolute activity (&gt;73 MBq) of injection areas correlated with successful intraoperative SLN detection. In a subgroup of 19 SLNs, a correlation between SPECT/CT-derived uptake and intraoperative count rate was found (R2 = 0.8; p &lt; 0.001). SLN detection in EC patients depended on high radiotracer activity at the cervical injection site. Quantitative SPECT/CT could predict successful intraoperative SLN detection and may help to optimize injection technique.
Induction of LTD-like corticospinal plasticity by low-frequency rTMS depends on pre-stimulus phase of sensorimotor μ-rhythm
2020-09-17

The level of corticospinal depolarization reflected by phase of the μ-oscillation determines the degree of corticospinal plasticity induced by low-frequency rTMS, a finding that may guide future personalized therapeutic stimulation.
Regional patterns of diachronic technological change in the Howiesons Poort of southern Africa
2020-09-17

The Howiesons Poort (HP) of southern Africa plays an important role in models on the early behavioral evolution of Homo sapiens. The HP is often portrayed as a coherent MSA industry characterized by early complex material culture. Recent work has emphasized parallel technological change through time across southern Africa potentially driven by ecological adaptations or demographic change. Here we examine patterns of diachronic variation within the HP and evaluate potential causal factors behind these changes. We test previous temporal assessments of the technocomplex at the local and regional level based on high-resolution quantitative data on HP lithic assemblages from Sibudu (KwaZulu-Natal) and comparisons with other southern African sites. At Sibudu, consistent unidirectional change in lithic technology characterizes the HP sequence. The results show a gradual reduction in typical HP markers such as the proportion of blades, backed pieces, and HP cores, as well as declining size of blades and backed artifacts. Quantitative comparisons with seven HP sites in South Africa suggest that lithic technology varies between regions over time instead of following similar changes. Concerning hypotheses of causal drivers, directional changes in lithic technology at Sibudu covary with shifting hunting patterns towards larger-sized bovids and a gradual opening of the vegetation. In contrast, variation in lithic technology shows little association with site use, mobility patterns or demographic expansions. Unlike at Sibudu, diachronic changes at other HP sites such as Diepkloof, Klasies River and Klipdrift appear to be associated with aspects of mobility, technological organization and site use. The regional diachronic patterns in the HP partly follow paleoclimatic zones, which could imply different ecological adaptations and distinct connection networks over time. Divergent and at times decoupled changes in lithic traits across sites precludes monocausal explanations for the entire HP, supporting more complex models for the observed technological trajectories.
Evaluating upfront high-dose consolidation after R-CHOP for follicular lymphoma by clinical and genetic risk models
2020-09-17

Abstract High-dose therapy and autologous stem cell transplantation (HDT/ASCT) is an effective salvage treatment for eligible patients with follicular lymphoma (FL) and early progression of disease (POD). Since the introduction of rituximab, HDT/ASCT is no longer recommended in first remission. We here explored whether consolidative HDT/ASCT improved survival in defined subgroups of previously untreated patients. We report survival analyses of 431 patients who received frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for advanced FL, and were randomized to receive consolidative HDT/ASCT. We performed targeted genotyping of 157 diagnostic biopsies, and calculated genotype-based risk scores. HDT/ASCT improved failure-free survival (FFS; hazard ratio [HR], 0.8, P = .07; as-treated: HR, 0.7, P = .04), but not overall survival (OS; HR, 1.3, P = .27; as-treated: HR, 1.4, P = .13). High-risk cohorts identified by FL International Prognostic Index (FLIPI), and the clinicogenetic risk models m7-FLIPI and POD within 24 months–prognostic index (POD24-PI) comprised 27%, 18%, and 22% of patients. HDT/ASCT did not significantly prolong FFS in high-risk patients as defined by FLIPI (HR, 0.9; P = .56), m7-FLIPI (HR, 0.9; P = .91), and POD24-PI (HR, 0.8; P = .60). Similarly, OS was not significantly improved. Finally, we used a machine-learning approach to predict benefit from HDT/ASCT by genotypes. Patients predicted to benefit from HDT/ASCT had longer FFS with HDT/ASCT (HR, 0.4; P = .03), but OS did not reach statistical significance. Thus, consolidative HDT/ASCT after frontline R-CHOP did not improve OS in unselected FL patients and subgroups selected by genotype-based risk models.
Consequences of Cognitive Offloading: Boosting Performance But Diminishing Memory
2020-09-17

Modern technical tools such as tablets allow for the temporal externalization of working memory processes (i.e. cognitive offloading). Although such externalizations support immediate performance on different tasks, little is known about potential long-term consequences of offloading behavior. In the current set of experiments, we studied the relationship between cognitive offloading and subsequent memory for the offloaded information as well as the interplay of this relationship with the goal to acquire new memory representations. Our participants solved the Pattern Copy Task, in which we manipulated the costs of cognitive offloading and the awareness of a subsequent memory test. In Experiment 1 (N = 172), we showed that increasing the costs for offloading induces reduced offloading behavior. This reduction in offloading came along with lower immediate task performance but more accurate memory in an unexpected test. In Experiment 2 (N = 172), we confirmed these findings and observed that offloading behavior remained detrimental for subsequent memory performance when participants were aware of the upcoming memory test. Experiment 3 (N = 172) additionally showed that resources released by cognitive offloading are not necessarily “lost”. Those participants who were forced to offload maximally but were aware of the memory test could almost completely counteract the negative impact of offloading on memory. Therefore, cognitive offloading is not detrimental to memory acquisition under all circumstances. Our experiments highlight the importance of the explicit goal to acquire new memory representations when relying on technical tools as offloading did have detrimental effects on memory without such a goal.
Unraveling the Developmental Dynamic of Visual Exploration of Social Interactions in Autism
2020-09-17

Abstract Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.
Lateral Suboccipital Approach in Semisitting Position for Resection of Vagal Schwannoma: 2-Dimensional Operative Video
2020-09-17

Abstract We present a case of a sizeable vagal schwannoma that was resected through a lateral suboccipital approach in semisitting position. An extra-axial lesion, occupying the left cerebellomedullary cistern and extending from the pontomedullary junction to the jugular foramen was incidentally discovered in a 40-year-old woman afflicted with secondary progressive multiple sclerosis during repeated magnetic resonance imaging (Fig. 1). On physical examination, a mild deviation of the uvula to the right and a diminished gag reflex were observed. The patient was referred to our department after considerable growth of the lesion was noted and a broad interdisciplinary consensus was reached to treat the lesion surgically. A gross total resection was achieved, histopathology confirmed a WHO I schwannoma with a low proliferation index. Postoperative dysphonia resolved completely within a few weeks, there was no collateral neurological deficit and especially no functional dysphagia. At 3-year follow-up, there was no indication of residual or recurrence. This 2-dimensional video demonstrates pre- and postoperative imaging, positioning and set-up of operating room, anatomical and surgical nuances of the skull base approach, and the operative technique for microdissection of the schwannoma from the critical neurovascular structures (Fig. 2). In summary, the lateral suboccipital approach in semisitting position is a powerful tool in the armamentarium for the microsurgical management of various pathologies residing in the posterior cranial fossa, especially large and vascularized schwannomas. Provided the necessary anesthesiological precautions and intraoperative procedures the semisitting position is safe and effective. The link to the video can be found at: https://youtu.be/-9o_qJGkQhg.