julilili42/papers huggingface dataset:
Post-Laramide, Eocene epeirogeny in central Colorado—The result of a mantle drip?
2022-05-12

Abstract The Southern Rocky Mountains first rose during the Laramide Orogeny (ca. 75–45 Ma), but today's mountains and adjacent Great Plains owe their current height to later epeirogenic surface uplift. When and why epeirogeny affected the region are controversial. Sedimentation histories in two central Colorado basins, the South Park–High Park and Denver basins, shifted at 56–54 Ma from an orogenic to an epeirogenic pattern, suggesting central Colorado experienced epeirogeny at that time. To interrogate that hypothesis, we analyzed thermal histories for seven samples from central Colorado's Arkansas Hills and High Park using thermochronometers with closure temperatures below ~180 °C, enabling us to track sample exhumation from ~5–7 km depth. Three samples are from the Cretaceous Whitehorn pluton, and four are Precambrian granitoids. All zircon and titanite (U-Th)/He dates (ZHe and THe) and one apatite fission-track (AFT) date are similar to the 67 Ma pluton emplacement age. Whitehorn dates using the lower-temperature apatite (U-Th)/He (AHe) thermochronometer are 55–41 Ma. These data require two exhumation episodes, one ca. 67–60 Ma, the second beginning at 54–46 Ma. The pluton reached the surface by 37 Ma, based on the age of volcanic tuff filling a pluton-cutting paleovalley. The Precambrian samples do not further refine this thermal history owing to the comparatively higher He closure temperature of their more radiation-damaged apatite. Laramide crustal shortening caused 67–60 Ma exhumation. Arkansas Hills shortening ended before 67 Ma, so shortening could not have caused the exhumation event that began 54–46 Ma; thermochronology supports the Eocene epeirogeny hypothesis. Epeirogeny affected &amp;gt;2.0 × 104 km2, from the Sawatch Range to the Denver Basin. We attribute epeirogeny to an Eocene mantle drip that likely triggered subsequent drips, causing younger exhumation events in adjacent areas.
Pemphigus Foliaceus Autoantibodies Induce Redistribution Primarily of Extradesmosomal Desmoglein 1 in the Cell Membrane
2022-05-12

The autoimmune dermatosis pemphigus foliaceus (PF) is predominantly caused by IgG autoantibodies against the desmosomal cadherin desmoglein (Dsg) 1. The exact mechanisms that lead to the characteristic epidermal blistering are not yet fully understood. In the present study, we used a variety of biophysical methods to examine the fate of membrane-bound Dsg1 after incubation with PF patients’ IgG. Dispase-based dissociation assays confirmed that PF-IgG used for this study reduced intercellular adhesion in a manner dependent on phospholipase C (PLC)/Ca 2+ and extracellular signal-regulated kinase (ERK) 1/2 signaling. Atomic force microscopy (AFM) revealed that Dsg1 binding on single molecule level paralleled effects on keratinocyte adhesion under the different conditions. Stimulated emission depletion (STED) super-resolution microscopy was used to investigate the localization of Dsg1 after PF-IgG incubation for 24 h. Under control conditions, Dsg1 was found to be in part co-localized with desmoplakin and thus inside of desmosomes as well as extra-desmosomal along the cell border. Incubation with PF-IgG reduced the extra-desmosomal Dsg1 fraction. In line with this, fluorescence recovery after photobleaching (FRAP) experiments demonstrated a strongly reduced mobility of Dsg1 in the cell membrane after PF-IgG treatment indicating remaining Dsg1 molecules were primarily located inside desmosomes. Mechanistically, experiments confirmed the involvement of PLC/Ca 2+ since inhibition of PLC or 1,4,5-trisphosphate (IP3) receptor to reduce cytosolic Ca 2+ reverted the effects of PF-IgG on Dsg1 intra-membrane mobility and localization. Taken together, our findings suggest that during the first 24 h PF-IgG induce redistribution predominantly of membrane-bound extradesmosomal Dsg1 in a PLC/Ca 2+ dependent manner whereas Dsg1-containing desmosomes remain.
Applying Tissue Separation and Untargeted Metabolomics to Understanding Lipid Saturation Kinetics of Host Mitochondria and Symbiotic Algae in Corals Under High Temperature Stress
2022-05-12

Untargeted metabolomics is a powerful tool for profiling the biochemical phenotypes of organisms and discovering new metabolites that drive biological function and might be exploited as pharmaceutical leads. Yet, connecting physiological processes to metabolites detected remains a challenge due to the lack of structural and activity annotations and the underlying complexity of mixed samples (e.g., multiple microorganisms, organelles, etc.). To simplify this biological complexity, we separated coral holobionts into host mitochondria and their algal symbionts prior to LC-MS/MS-based untargeted metabolomic analysis followed by molecular networking. We found distinct metabolomic profiles between tissue fractions. Notably, 14% of metabolites detected were only observed in the mitochondria and algal symbionts, not in the holobiont, and thus were masked when the bulk (holobiont) sample was analyzed. The utility of tissue separation for hypothesis testing was assessed using a simple temperature experiment. We tested the hypothesis that membrane lipids of the coral mitochondria and algal symbionts become more saturated at higher temperatures to maintain membrane rigidity. While the holobiont metabolite profiles showed little change in response to elevated temperature, there was a change in lipid saturation of both fractions through time. The fatty acid saturation of both the coral mitochondria and the algal symbionts shifted upon exposure to higher temperatures (1 h) then returned to ambient saturation levels by 4 h, indicating rapid acclimatization to warmer water. Surprisingly, the fractions deviated in opposite directions: during the first hour of the experiment, the mitochondria showed an increase in saturated lipid concentrations, while the algal symbionts showed an increase in unsaturated lipids. Partitioning the holobiont prior to untargeted metabolomic analysis revealed disparate responses to environmental stress that would have gone undetected if only the holobiont/bulk tissue was analyzed. This work illustrates rapid physiological acclimatization to environmental changes in specific host organelles and symbionts, though via different paths.
Gateway Identity and Spatial Remapping in a Combined Grid and Place Cell Attractor
2022-05-12

Abstract The spatial specificities of hippocampal place cells, i.e., their firing fields, are subject to change if the rat enters a new compartment in the experimental maze. This effect is known as remapping. It cannot be explained from path integration (grid cell activity) and local sensory cues alone but requires additional knowledge of the different compartments in the form of context recognition at the gateways between them. Here we present a model for the hippocampalentorhinal interplay in which the activity of place and grid cells follows a joint attractor dynamic. Place cells depend on the current grid cell activity but can also reset the grid cell activity in the remapping process. Remapping is triggered by the passage through a gateway. When this happens, a previously stored pattern of place cell activity associated with the gateway is reactivated from a “gateway database”. The joint attractor will then reinstate the grid cell pattern that was active when the gateway had first been learned and path integration can proceed from there. The model is tested with various mazes used in the experimental literature and reproduces the published results, and we make predictions for remapping in a new maze type. We propose the involvement of memory in the form of “gate cells” that drive the place cells and with them the joint hippocampal-entorhinal loop into the corresponding attractor whenever a compartment is entered.
Reply on RC3
2022-05-12

<strong class="journal-contentHeaderColor">Abstract.</strong> Soil erosion continues to be one of the most serious environmental problems of our time and is exacerbated by progressive climate change. Until now, forests have been considered an ideal erosion control. However, even minor disturbances of the forest floor, for example, from heavy vehicles used for timber harvesting, can cause substantial sediment transport. An important countermeasure is the quick restoration of the uncovered soil surface by vegetation. To date, very little attention has been paid to the development of nonvascular plants, such as bryophytes, in disturbed areas of temperate forests and their impact on soil erosion. This study examined the natural succession of pioneer vegetation in skid trails on four soil substrates in a central European temperate forest and investigated their influence on soil erosion. For this purpose, rainfall simulations were conducted on small-scale runoff plots, and vegetation was continuously surveyed during the same period, primarily to map the development of bryophytes and the occurrence of biological soil crusts (biocrusts). Biocrusts appeared immediately after disturbance, consisting primarily of bryophyte protonemata and cyanobacteria as well as coccoid and filamentous algae that lost their biocrust characteristics as succession progressed. They were present from April to July 2019, with a particular expression in the skid trail that was on shale clay (Psilonotenton Formation) and silty clay loam substrate. In general, skid trails on clayey substrates showed considerably higher bryophyte cover and species richness. Although bryophytes were subsequently overtopped by vascular plants, they managed to coexist until their growth was restricted due to leaf litter fall. <i>Brachythecium rutabulum</i> and <i>Oxyrrhynchium hians</i> were the most important and persistent pioneer bryophyte species, while <i>Dicranella schreberiana</i> and <i>Pohlia lutescens</i> were volatile and quickly disappeared after spreading in the summer. Sediment discharge was 22 times higher on disturbed bare soil compared with undisturbed forest soil and showed the largest sediment removal in the wheel tracks. Counteracting this, soil erosion decreased with the recovery of surface vegetation and was particularly reduced with growing pioneer biocrusts in summer, but it again increased in winter, when vascular vegetation became dominant. This leads to the conclusion that the role of bryophyte-dominated biocrusts in forests has been underestimated so far, and they can contribute more to soil conservation at specific times of succession than vascular plants.
Mast cell infiltration of the choroid and protease release are early events in age-related macular degeneration associated with genetic risk at both chromosomes 1q32 and 10q26
2022-05-13

Significance Genome-wide association studies have identified two major risk loci for age-related macular degeneration (AMD) on chromosome (Chr) 1 and Chr10. Here, we use proteomics to analyze submacular stromal tissue punches from older eye donors without AMD, comparing tissue from donors who were homozygous for high-risk alleles at Chr1 or Chr10 with tissue from donors with low risk at these two loci. A common change found in Chr1/Chr10–risk eyes was increased mast cell proteases, and immunohistochemistry confirmed the presence of increased mast cell numbers. This study, therefore, provides a unifying mechanistic link between Chr1 and Chr10 risk and suggests that mast cell infiltration of the choroid and degranulation are early events in AMD pathogenesis.
The efficacy of a transdiagnostic emotion regulation skills training in the treatment of binge‐eating disorder—Results from a randomized controlled trial
2022-05-13

Abstract Objectives Deficits in emotion regulation (ER) have been shown to be associated with binge‐eating disorder (BED). To further clarify the causal nature of this association, we tested whether systematically enhancing ER skills would reduce symptoms of BED. Methods We randomly allocated N = 101 individuals meeting the criteria for BED to a transdiagnostic ER skills training or to a waitlist control condition (WLC). Primary outcome was the reduction in binges during the treatment‐vs.‐waiting period as assessed with the Eating Disorder Examination (EDE) interview. Results Mixed‐model ANOVAs indicated that the average pre‐to‐post decrease in binges assessed with the EDE was significantly greater in the ER skills training condition than in the WLC ( d = 0.66). These effects were stable over the 6‐month follow‐up period ( d = 0.72). Remission rates at post/follow‐up were 34.4/45.0% in the skills training and 7.5/20.0% in the WLC. Additionally, we found a greater reduction in general eating disorder psychopathology, of food consumption in a bogus taste test and of depression in the ER skills training condition. Moreover, the greater reduction in binge‐eating episodes in the training condition was (partially) mediated by a greater increase in ER skills. Conclusions The findings provide further support for the assumed importance of deficits in ER as a maintaining factor and, hence, as a target in the treatment of BED. As ER skills trainings have been shown to also reduce other kinds of psychopathology, they might be considered a promising transdiagnostic add‐on component to disorder‐specific interventions.
Moderate DNA methylation changes associated with nitrogen remobilization and leaf senescence in Arabidopsis
2022-05-13

Abstract The lifespan of plants is restricted by environmental and genetic components. Following the transition to reproductive growth, leaf senescence ends cellular life in monocarpic plants to remobilize nutrients to storage organs. In Arabidopsis, we initially observed altered leaf to seed ratios, faster senescence progression, altered leaf nitrogen recovery after transient nitrogen removal, and ultimately enhanced nitrogen remobilization from the leaves in two methylation mutants (ros1 and the triple dmr1/2 cmt3 knockout). Analysis of the DNA methylome in wild type Col-0 leaves identified an initial moderate decline of cytosine methylation with progressing leaf senescence, predominantly in the CG context. Late senescence was associated with moderate de novo methylation of cytosines, primarily in the CHH context. Relatively few differentially methylated regions, including one in the ROS1 promoter linked to down-regulation of ROS1, were present, but these were unrelated to known senescence-associated genes. Differential methylation patterns were identified in transcription factor binding sites, such as the W-boxes that are targeted by WRKYs. Methylation in artificial binding sites impaired transcription factor binding in vitro. However, it remains unclear how moderate methylome changes during leaf senescence are linked with up-regulated genes during senescence.
Where and What
2022-05-13

Human drivers use their attentional mechanisms to focus on critical objects and make decisions while driving. As human attention can be revealed from gaze data, capturing and analyzing gaze information has emerged in recent years to benefit autonomous driving technology. Previous works in this context have primarily aimed at predicting "where" human drivers look at and lack knowledge of "what" objects drivers focus on. Our work bridges the gap between pixel-level and object-level attention prediction. Specifically, we propose to integrate an attention prediction module into a pretrained object detection framework and predict the attention in a grid-based style. Furthermore, critical objects are recognized based on predicted attended-to areas. We evaluate our proposed method on two driver attention datasets, BDD-A and DR(eye)VE. Our framework achieves competitive state-of-the-art performance in the attention prediction on both pixel-level and object-level but is far more efficient (75.3 GFLOPs less) in computation.
U-HAR
2022-05-13

After the success of smartphones and smartwatches, smart glasses are expected to be the next smart wearable. While novel display technology allows the seamlessly embedding of content into the FOV, interaction methods with glasses, requiring the user for active interaction, limiting the user experience. One way to improve this and drive immersive augmentation is to reduce user interactions to a necessary minimum by adding context awareness to smart glasses. For this, we propose an approach based on human activity recognition, which incorporates features, derived from the user's head- and eye-movement. Towards this goal, we combine an commercial eye-tracker and an IMU to capture eye- and head-movement features of 7 activities performed by 20 participants. From a methodological perspective, we introduce U-HAR, a convolutional network optimized for activity recognition. By applying a few-shot learning, our model reaches an macro-F1-score of 86.59%, allowing us to derive contextual information.
Protocol for the process evaluation of a counselling intervention designed to educate cancer patients on complementary and integrative health care and promote interprofessional collaboration in this area (the CCC-Integrativ study)
2022-05-13

Background Conducting a process evaluation is essential to understand how health interventions work in different healthcare settings. Particularly in the case of complex interventions, it is important to find out whether the intervention could be carried out as planned and which factors had a beneficial or hindering effect on its implementation. The aim of this study is to present the detailed protocol of the process evaluation embedded in the controlled implementation study CCC-Integrativ aiming to implement an interprofessional counselling program for cancer patients on complementary and integrative health care (CIH). Methods This mixed methods study will draw upon the “Consolidated Framework for Implementation Research” (CFIR) combined with the concept of “intervention fidelity” to evaluate the quality of the interprofessional counselling sessions, to explore the perspective of the directly and indirectly involved healthcare staff, as well as to analyze the perceptions and experiences of the patients. The qualitative evaluation phase consists of analyzing audio-recorded counselling sessions, as well as individual and group interviews with the involved persons. The quantitative evaluation phase applies questionnaires which are distributed before (T0), at the beginning (T1), in the middle (T2) and at the end (T3) of the intervention delivery. Discussion This protocol provides an example of how a process evaluation can be conducted parallel to a main study investigating and implementing a complex intervention. The results of this mixed methods research will make it possible to identify strengths and weaknesses of the team-based intervention, and to target more specifically the key factors and structures required to implement healthcare structures to meet patients’ unmet needs in the context of CIH. To our knowledge, this study is the first applying the CFIR framework in the context of interprofessional CIH counselling, and its results are expected to provide comprehensive and multidisciplinary management of cancer patients with complex supportive healthcare needs.
Dysregulated Exosomes Result in Suppression of the Immune Response of Pregnant COVID-19 Convalescent Women
2022-05-13

A successful pregnancy outcome is dependent on a delicate balance between inflammatory and anti-inflammatory processes throughout the different trimesters. Interruption in this balance can lead to an adverse outcome resulting in pregnancy loss. Since late 2019, the emergence of the new SARS-CoV-2 virus has affected lives worldwide, including pregnant women; therefore, there is an urgent need to address different approaches in relation to prevention, diagnostics, and therapeutics. Early pregnancy is affected by SARS-CoV-2 infection leading to fetal demise. Available evidence also suggests that 90% of pregnant women infected with the SARS-CoV-2 virus seem to be asymptomatic. Nonetheless, it is still unclear how COVID-19 affects exosome production in pregnant women recovered from COVID-19 and how these exosomes regulate the adaptive immune response. In this study, we found several exosomes including CD9, CD31, CD40, CD45, CD41b, CD42a, CD62P, CD69, CD81, CD105, and HLA-DRDPDQ in the plasma of COVID-19-recovered pregnant women were significantly less abundant than the control group. Furthermore, to understand how these exosomes affect the adaptive immune response, we co-cultured the peripheral blood mononuclear cells (PBMCs) from healthy control (HC) pregnant women with exosomes of either Preg-HC or Preg-recovered COVID-19 women. We identified that Preg-recovered COVID-19 women have reduced capacity for the inflammatory cytokine TNF-α from cytotoxic CD8 + T cells. In summary, our study highlights that pregnant recovered COVID-19 women have reduced production of several exosomes and possess fewer immunogenic properties. Our study implicates that exosomes can control inflammation and antigen presentation capacity of immune cells, thus limiting the infection in pregnant women.
CD24: A Marker for an Extended Expansion Potential of Urothelial Cancer Cell Organoids In Vitro?
2022-05-13

Background: Bladder cancer is the most cost-intensive cancer due to high recurrence rates and long follow-up times. Bladder cancer organoids were considered interesting tools for investigating better methods for the detection and treatment of this cancer. Methods: Organoids were generated from urothelial carcinoma tissue samples, then expanded and characterized; the expression of immune modulatory antigens and tumor stem cells markers CD24 and CD44 was explored in early (P ≤ 3) and later (P ≥ 5) passages (P) by immunofluorescence and by quantitative PCR of cDNA. The expression of these factors was investigated in the corresponding cancer tissue samples by immunohistochemistry. Results: The expression of the PD-L1 was detected on some but not all organoids. CD276 and CD47 were observed on organoids in all passages investigated. Organoids growing beyond passage 8 expressed both CD24 and CD44 at elevated levels in early and late cultures. Organoids proliferating to the eighth passage initially expressed both CD24 and CD44, but lost CD24 expression over time, while CD44 remained. Organoids growing only up to the 6th passage failed to express CD24 but expressed CD44. Conclusions: The data indicate that the expression of CD24 in urothelial cancer cell organoids may serve as an indicator for the prolonged proliferation potential of the cells.
A Comprehensive Evaluation of Consensus Spectrum Generation Methods in Proteomics
2022-05-13

Spectrum clustering is a powerful strategy to minimize redundant mass spectra by grouping them based on similarity, with the aim of forming groups of mass spectra from the same repeatedly measured analytes. Each such group of near-identical spectra can be represented by its so-called consensus spectrum for downstream processing. Although several algorithms for spectrum clustering have been adequately benchmarked and tested, the influence of the consensus spectrum generation step is rarely evaluated. Here, we present an implementation and benchmark of common consensus spectrum algorithms, including spectrum averaging, spectrum binning, the most similar spectrum, and the best-identified spectrum. We have analyzed diverse public data sets using two different clustering algorithms (spectra-cluster and MaRaCluster) to evaluate how the consensus spectrum generation procedure influences downstream peptide identification. The BEST and BIN methods were found the most reliable methods for consensus spectrum generation, including for data sets with post-translational modifications (PTM) such as phosphorylation. All source code and data of the present study are freely available on GitHub at https://github.com/statisticalbiotechnology/representative-spectra-benchmark.