bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Continuum Solvent Models in Computational Homogeneous Catalysis
Authors: Norjmaa Gantulga , Ujaque Gregori , Lledós Agustí
Published: November 2021

In homogeneous catalysis solvent is an inherent part of the catalytic system. As such, it must be considered in the computational modeling. The most common approach to include solvent effects in quantum mechanical calculations is by means of continuum solvent models. When they are properly used, average solvent effects are efficiently captured, mainly those related with solvent polarity. However, neglecting atomistic description of solvent molecules has its limitations, and continuum solvent models all alone cannot be applied to whatever situation. In many cases, inclusion of explicit solvent molecules in the quantum mechanical description of the system is mandatory. The purpose of this article is to highlight through selected examples what are the reasons that urge to go beyond the continuum models to the employment of micro-solvated (cluster-continuum) of fully explicit solvent models, in this way setting the limits of continuum solvent models in computational homogeneous catalysis. These examples showcase that inclusion of solvent molecules in the calculation not only can improve the description of already known mechanisms but can yield new mechanistic views of a reaction. With the aim of systematizing the use of explicit solvent models, after discussing the success and limitations of continuum solvent models, issues related with solvent coordination and solvent dynamics, solvent effects in reactions involving small, charged species, as well as reactions in protic solvents and the role of solvent as reagent itself are successively considered.
Visualizing CAR-T cell Immunotherapy Using 3 Tesla Fluorine-19 MRI
Authors: Dubois Veronica P. , Sehl Olivia C. , Foster Paula J. , Ronald John A.
Published: November 2021

Purpose

Chimeric antigen receptor (CAR) T cell cancer immunotherapies have shown remarkable results in patients with hematological malignancies and represent the first approved genetically modified cellular therapies. However, not all blood cancer patients respond favorably, serious side effects have been reported, and the treatment of solid tumors has been a challenge. An imaging tool for visualizing the variety of CAR-T cell products in use and being explored could provide important patient-specific data on CAR-T cell location to inform on potential success or failure of treatment as well as off-target toxicities. Fluorine-19 (19F) magnetic resonance imaging (MRI) allows for the noninvasive detection of 19F perfluorocarbon (PFC) labeled cells. Our objective was to visualize PFC-labeled (PFC +) CAR-T cells in a mouse model of leukemia using clinical field strength (3 Tesla) 19F MRI and compare the cytotoxicity of PFC + versus unlabeled CAR-T cells.

Procedures

NSG mice (n = 17) received subcutaneous injections of CD19 + human B cell leukemia cells (NALM6) expressing firefly luciferase in their left hind flank (1 × 106). Twenty-one days later, each mouse received an intratumoral injection of 10 × 106 PFC + CD19-targeted CAR-T cells (n = 6), unlabeled CD19-targeted CAR-T cells (n = 3), PFC + untransduced T cells (n = 5), or an equivalent volume of saline (n = 3). 19F MRI was performed on mice treated with PFC + CAR-T cells days 1, 3, and 7 post-treatment. Bioluminescence imaging (BLI) was performed on all mice days − 1, 5, 10, and 14 post-treatment to monitor tumor response.

Results

PFC + CAR-T cells were successfully detected in tumors using 19F MRI on days 1, 3, and 7 post-injection. In vivo BLI data revealed that mice treated with PFC + or PFC − CAR-T cells had significantly lower tumor burden by day 14 compared to untreated mice and mice treated with PFC + untransduced T cells (p < 0.05). Importantly, mice treated with PFC + CAR-T cells showed equivalent cytotoxicity compared to mice receiving PFC − CAR-T cells.

Conclusions

Our studies demonstrate that clinical field strength 19F MRI can be used to visualize PFC + CAR-T cells for up to 7 days post–intratumoral injection. Importantly, PFC labeling did not significantly affect in vivo CAR-T cell cytotoxicity. These imaging tools may have broad applications for tracking emerging CAR-T cell therapies in preclinical models and may eventually be useful for the detection of CAR-T cells in patients where localized injection of CAR-T cells is being pursued.
Acute Stroke Treatment in an Anticoagulated Patient: When Is Thrombolysis an Option?
Authors: Siller Teresa , Chandratheva Arvind , Bücke Philipp , Werring David J. , Seiffge David
Published: November 2021

Purpose of Review

Direct oral anticoagulants (DOACs: the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban and the direct thrombin inhibitor dabigatran) are the mainstay of stroke prevention in patients with non-valvular atrial fibrillation (AF). Nevertheless, there is a residual stroke risk of 1–2% per year despite DOAC therapy. Intravenous thrombolysis (IVT) reduces morbidity in patients with ischemic stroke and improves functional outcome. Prior DOAC therapy is a (relative) contraindication for IVT but emerging evidence supports its use in selected patients.

Recent Findings

Recent observational studies highlighted that IVT in patients on prior DOAC therapy seems feasible and did not yield major safety issues. Different selection criteria and approaches have been studied including selection by DOAC plasma levels, non-specific coagulation assays, time since last intake, and prior reversal agent use. The optimal selection process is however not clear and most studies comprised few patients.

IVT in patients taking DOAC is a clinically challenging scenario. Several approaches have been proposed without major safety issues but current evidence is weak. A patient-oriented approach balancing potential benefits of IVT (i.e., amount of salvageable penumbra) against expected bleeding risk including appropriate monitoring of anticoagulant activity seem justified.
“I Have Been Born, Raised and Lived My Whole Life Here” – Perpetually on the Move While Remaining Still
Authors: Pedersen Oliver Clifford , Zittoun Tania
Published: November 2021

This article explores the story of Einar, a Faroese man who always lived within a 500-meters radius on the island of Suðuroy, who never felt “stuck” or “immobile” in the literal sense of the word. Studies have shown that staying is a process, as much as mobility; yet while mobility studies mainly show that imagination is an incentive to move, we argue that imagination may also actively support staying. Combining sociocultural psychology with mobility studies, we propose to explore the entanglement of symbolic mobility (a form of imagination) and various forms of geographical (im)mobility. Based on ethnographic fieldwork and hours of conversation, we present the case study of Einar’s life on his island. We follow the sociogenetic development of the island, and the expansion and contraction of the imaginative horizon over time. On this background, we then retrace the life of Einar and show how, within this transforming context, his imagination developed thanks to resources he could use from the mobility of technologies, ideas, and other people. Interestingly, at different bifurcation points, his symbolic mobility almost led him to move away but, at another point, helped him to refuse geographical mobility. Hence, he was always symbolically mobile while staying. We finally propose directions for generalising from this case study, and implications for cultural psychology and for mobility and migration studies.
Detecting Lies is a Child (Robot)’s Play: Gaze-Based Lie Detection in HRI
Authors: Pasquali Dario , Gonzalez-Billandon Jonas , Aroyo Alexander Mois , Sandini Giulio , Sciutti Alessandra , Rea Francesco
Published: November 2021

Robots destined to tasks like teaching or caregiving have to build a long-lasting social rapport with their human partners. This requires, from the robot side, to be capable of assessing whether the partner is trustworthy. To this aim a robot should be able to assess whether someone is lying or not, while preserving the pleasantness of the social interaction. We present an approach to promptly detect lies based on the pupil dilation, as intrinsic marker of the lie-associated cognitive load that can be applied in an ecological human–robot interaction, autonomously led by a robot. We demonstrated the validity of the approach with an experiment, in which the iCub humanoid robot engages the human partner by playing the role of a magician in a card game and detects in real-time the partner deceptive behavior. On top of that, we show how the robot can leverage on the gained knowledge about the deceptive behavior of each human partner, to better detect subsequent lies of that individual. Also, we explore whether machine learning models could improve lie detection performances for both known individuals (within-participants) over multiple interaction with the same partner, and with novel partners (between-participant). The proposed setup, interaction and models enable iCub to understand when its partners are lying, which is a fundamental skill for evaluating their trustworthiness and hence improving social human–robot interaction.
The Therapeutic Effects of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells on Scleroderma
Authors: Yu Yue , Shen Liangliang , Xie Xiaoyun , Zhao Jingjun , Jiang Miao
Published: November 2021

Background:

Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. The mortality of scleroderma has remained high due to a lack of effective treatments. However, exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may also act as candidates for treating scleroderma.

Methods:

Mice with scleroderma received a single 50 μg HUMSCs-Ex. HUMSCs-Ex was characterized using transmission electron microscopy, nanoparticle tracking analysis and nanoflow cytometry. The therapeutic efficacy was assessed using histopathology, immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blot.

Results:

HUMSCs-Ex ameliorated the deposition of extracellular matrix and suppressed the epithelial-mesenchymal transition process, and the effects lasted at least three weeks. In addition, HUMSCs-Ex promoted M1 macrophage polarization and inhibited M2 macrophage polarization, leading to the restoration of the balance of M1/M2 macrophages.

Conclusion:

We investigated the potential antifibrotic and anti-inflammatory effects of HUMSCs-Ex in a bleomycin-induced mouse model of scleroderma. So HUMSCs-Ex could be considered as a candidate therapy for scleroderma.
Obesity in the News
Authors: Brookes Gavin , Baker Paul
Published: November 2021

Obesity is a pressing social issue and a persistently newsworthy topic for the media. This book examines the linguistic representation of obesity in the British press. It combines techniques from corpus linguistics with critical discourse studies to analyse a large corpus of newspaper articles (36 million words) representing ten years of obesity coverage. These articles are studied from a range of methodological perspectives, and analytical themes include variation between newspapers, change over time, diet and exercise, gender and social class. The volume also investigates the language that readers use when responding to obesity representations in the context of online comments. The authors reveal the power of linguistic choices to shame and stigmatise people with obesity, presenting them as irresponsible and morally deviant. Yet the analysis also demonstrates the potential for alternative representations which place greater focus on the role that social and political forces play in this topical health issue.
“What Are We?”: Latino Politics, Identity, and Memory in the 1983 Chicago Mayoral Election
Authors: Sánchez Jaime
Published: November 2021

The 1983 Chicago mayoral election, which polarized Black and white voters, left the nascent Latino electorate in an uncertain position. A reevaluation of this election clarifies the impact of Black mayoral candidate Harold Washington, whose candidacy laid bare significant political divisions and anti-Black sentiment among Latinos as they grappled with their relationship to whiteness. Divisions aside, Washington's effort to court the Latino vote helped legitimate a monolithic, panethnic label in Chicago politics, as evidenced by organizational records, campaign advertising, electoral data, and bilingual media coverage. Reframing the 1983 election as a dual process of race making and panethnic labeling bridges scholarship on Black mayors, Latino politics, and urban history, and questions an enduring political memory of 1983 that has obscured both Latino anti-Blackness and the fragility of Latino unity.
Purpose of the Joint Discussion D
Authors: Böhm K. H.
Published: November 2021

The discovery of oscillatory motion in the solar photosphere and of the ‘super-granulation’ in the chromosphere has changed our ideas about the hydrodynamics of the solar atmosphere considerably. In this Joint Discussion we shall mainly consider the theoretical implications of this change. As the ultimate aim is an understanding of the hydrodynamics in all stellar atmospheres—not only in the Sun, some discussion of other stellar atmospheres will be included.
Proceedings of the Joint Discussion: Radar Determinations of Planetary Motions
Authors: Shapiro I. I.
Published: November 2021

Radar echoes have already been detected from Venus, Mercury, Mars, and Jupiter. Time delay measurements of high precision between Earth and Venus, as well as between Earth and Mercury, have disclosed significant deviations from the published ephemerides of these planets. Although new simultaneous solutions for the A.U., the relevant planetary masses, radii, and orbital elements have not yet been carried out, preliminary analysis indicates that the light-second equivalent of the A.U. is 499.0050 ± 0.0004 and that the corresponding kilometer equivalent is about 149 598 000 ± 100 (using c = 299 792.5 km/sec). The same analysis shows that, with respect to Earth, both Venus and Mercury seem to be ahead in their orbits relative to predictions. The radius of Venus appears to be about 6100 ± 50 km, in agreement with the most accurate optical determination. Doppler spread measurements show Venus to have a retrograde rotation with a period of about 247 ± 5 days. The celestial latitude of its axis is about – 85 ± 2 degrees.
Vision-based pose estimation of craniocervical region: experimental setup and saw bone-based study
Authors: Zubair Mohammad , Kansal Sachin , Mukherjee Sudipto
Published: November 2021

This article discusses the intervertebral motion present in the craniovertebral junction (CVJ) region. The CVJ region is bounded by the first three vertebras from the spinal column. It helps in bringing most of the neck motion. Intervention in this region requires surgery in which an implant is placed to stabilize the whole system. The various available implants need to undergo performance evaluation as their performance varies from region and anatomical diversity. For the Indian population, we are targeting to evaluate the performance of such an implant, testing it into a cadaver. The region of interest will be loaded as per the loading condition of an average human. Motion in these regions is evaluated using the camera. A preliminary test was done on a saw bone model of CVJ to assess the performance of segmentation methods. Multiple such ArUco markers are used to increase pose accuracy further, and the pose of the entire board of multiple tags provides us with reliable pose estimation. The absolute error ranged from a minimum of 0.1 mm to a maximum of 16 mm. At the same time, the mean and median absolute errors were 3.8961 mm and 3.35 mm. By considering the absolute lengths, the percentage error showed the following trends. The percentage error was between 3.9168% and 0.0230%.
Truth and Reparation for the U.S. Imprisonment and Policing Regime
Authors: Page Jennifer M. , King Desmond
Published: November 2021

In the literature on transitional justice, there is disagreement about whether countries like the United States can be characterized as transitional societies. Though it is widely recognized that transitional justice mechanisms such as truth commissions and reparations can be used by Global North nations to address racial injustice, some consider societies to be transitional only when they are undergoing a formal democratic regime change. We conceptualize the political situation of low-income Black communities under the U.S. imprisonment and policing regime in terms of three criteria for identifying transitional contexts:normalized collective and political wrongdoing,pervasive structural inequality, and thefailure of the rule of law.That these criteria are met, however, does not necessarily mean that a transition is taking place. Drawing on the American political development and abolition democracy literatures, we discuss what it would mean for the United States to transition out of its present imprisonment and policing regime. A transitional justice perspective shows the importance of not only pushing for truth and reparation, but for an actual transition.
The value of agrobiodiversity: an analysis of consumers preference for tomatoes
Authors: Posadinu Chiara M. , Rodriguez Monica , Madau Fabio , Attene Giovanna
Published: November 2021

The valorization of plant genetic resources and their direct use in local markets can make a significant contribution to the preservation of agrobiodiversity, while also contributing to the sustainability of rural communities. Indeed, plant genetic resources are a precious source of genes, and they represent an important crop heritage for the quality and sensory characteristics that are required by both farmers and consumers. However, an efficient strategy of agrobiodiversity conservation is strictly connected to product marketability and to consumer preferences. In the present study, choice experiments that involved 920 consumers were carried out to determine their willingness to pay for ancient local tomato varieties (landraces) rather than commercial varieties based on their preferences, and to determine how much they valued these products. The results obtained indicate that consumers are willing to pay premium prices for ancient local tomato varieties (an additional €0.90 kg−1), thus demonstrating their increasing attention to sustainable food and the willingness to contribute to agrobiodiversity conservation and enhancement. These results provide the basis for planning strategies and programs to support the cultivation of these landraces and the development of regional and national markets to acknowledge their characteristics, which will considerably increase the effectiveness and efficiency of conservation strategies.
Unexpected Magnetic Behavior of Natural Hematite‐Bearing Rocks at Low Temperatures
Authors: Abrajevitch Alexandra , Roberts Andrew P. , Pillans Brad J. , Hori Rie S.
Published: November 2021

Hematite is a commonly occurring magnetic mineral in nature that has numerous scientific and technological applications. A characteristic property of hematite is a low‐temperature spin‐flop transition called the Morin transition. Above the transition temperature, hematite is a canted antiferromagnet that can carry a remanent magnetization. Below this transition, spin canting disappears and hematite becomes a true antiferromagnet although a small defect moment is usually preserved. We observe Morin transition behavior in natural samples that has not been reported before for hematite. During repeated thermal cycling of a remanent magnetization acquired at room temperature, the remanence intensity at the end of the cycle oscillates between a high remanence state at the end of odd‐numbered cycles and a low remanence state (LRS) at the end of even‐numbered cycles. Alternation of the high and LRSs during repeated thermal cycling points to hysteretic behavior of the spin‐flop process, likely due to sublattice magnetization alignment switches along different easy magnetization axes in samples with preferred crystallographic orientations of hematite particles. We report these observations to seek to expand explanations of the magnetism of hematite.
Machine‐Learning Based Reconstructions of Past Regional Sea Level Variability From Proxy Data
Authors: Radin Cristina , Nieves Veronica
Published: November 2021

The analysis of past regional climate‐related sea level variations has important implications for diagnosing changes in future sea level driven by climate fluctuations. As the climate changes, there is a need for new explanatory variables of within‐region climate factors and for more complex methods able to identify nonlinear relationships, such as machine learning algorithms. This study demonstrates the application of a new machine learning‐based methodology to reconstruct historical sea level tide gauge records from proxy data (i.e., upper‐ocean temperature estimates in open ocean regions), which provide a reasonably good dynamical representation of coastal sea level variations linked to slow and persistent natural processes like internal climate variability. The learning performance of our method was evaluated against observations of multiple stations and across a variety of model reconstructions, as shown and evidenced by the results.
The Energy and Mass Balance of Peruvian Glaciers
Authors: Fyffe Catriona L. , Potter Emily , Fugger Stefan , Orr Andrew , Fatichi Simone , Loarte Edwin , Medina Katy , Hellström Robert Å. , Bernat Maud , Aubry‐Wake Caroline , Gurgiser Wolfgang , Perry L. Baker , Suarez Wilson , Quincey Duncan J. , Pellicciotti Francesca
Published: November 2021

Peruvian glaciers are important contributors to dry season runoff for agriculture and hydropower, but they are at risk of disappearing due to climate change. We applied a physically based, energy balance melt model at five on‐glacier sites within the Peruvian Cordilleras Blanca and Vilcanota. Net shortwave radiation dominates the energy balance, and despite this flux being higher in the dry season, melt rates are lower due to losses from net longwave radiation and the latent heat flux. The sensible heat flux is a relatively small contributor to melt energy. At three of the sites the wet season snowpack was discontinuous, forming and melting within a daily to weekly timescale, and resulting in highly variable melt rates closely related to precipitation dynamics. Cold air temperatures due to a strong La Niña year at Shallap Glacier (Cordillera Blanca) resulted in a continuous wet season snowpack, significantly reducing wet season ablation. Sublimation was most important at the highest site in the accumulation zone of the Quelccaya Ice Cap (Cordillera Vilcanota), accounting for 81% of ablation, compared to 2%–4% for the other sites. Air temperature and precipitation inputs were perturbed to investigate the climate sensitivity of the five glaciers. At the lower sites warmer air temperatures resulted in a switch from snowfall to rain, so that ablation was increased via the decrease in albedo and increase in net shortwave radiation. At the top of Quelccaya Ice Cap warming caused melting to replace sublimation so that ablation increased nonlinearly with air temperature.
Ice Nucleating Particle Connections to Regional Argentinian Land Surface Emissions and Weather During the Cloud, Aerosol, and Complex Terrain Interactions Experiment
Authors: Testa Baptiste , Hill Thomas C. J. , Marsden Nicholas A. , Barry Kevin R. , Hume Carson C. , Bian Qijing , Uetake Jun , Hare Hannah , Perkins Russell J. , Möhler Ottmar , Kreidenweis Sonia M. , DeMott Paul J.
Published: November 2021

Here, we present a multi‐season study of ice‐nucleating particles (INPs) active via the immersion freezing mechanism, which took place in north‐central Argentina, a worldwide hotspot for mesoscale convective storms. INPs were measured untreated, after heating to 95°C, and after hydrogen peroxide digestion. No seasonal cycle of INP concentrations was observed. Heat labile INPs, which we define as “biological” herein, dominated the population active at −5 to −20°C, while non‐heat‐labile organic INPs (decomposed by peroxide) dominated at lower temperatures, from −20 to −28°C. Inorganic INPs (remaining after peroxide digestion), were minor contributors to the overall INP activity. Biological INP concentration active around −12°C peaked during rain events and under high relative humidity, reflecting emission mechanisms independent of the background aerosol concentration. The ratio of non‐heat‐labile organic and inorganic INPs was generally constant, suggesting they originated from the same source, presumably from regional arable topsoil based on air mass histories. Single particle mass spectrometry showed that soil particles aerosolized from a regionally common agricultural topsoil contained known mineral INP sources (K‐feldspar and illite) as well as a significant organic component. The INP activity observed in this study correlates well with agricultural soil INP activities from this and other regions of the world, suggesting that the observed INP spectra might be typical of many arable landscapes. These results demonstrate the strong influence of regional continental landscapes, emitting INPs of types that are not yet well represented in global models.
Contributions of Anthropogenic Forcings to Evapotranspiration Changes Over 1980–2020 Using GLEAM and CMIP6 Simulations
Authors: Liu Jianyu , Zhang Jiawen , Kong Dongdong , Feng Xingyu , Feng Shuyun , Xiao Mingzhong
Published: November 2021

Anthropogenic impacts on terrestrial evapotranspiration (ET) changes during 1980–2020 were evaluated based on newly released observed‐based GLEAM ET and Coupled Model Intercomparison Project Phase 6 (CMIP6) through optional fingerprint method. Global assessments show that anthropogenic forcings dominate the increasing ET trend, other than natural forcing (NAT). On the global scale, anthropogenic forcings explain ∼84.2% of the observed ET trend, while the signal of natural forcing cannot be detected. Among anthropogenic forcings, greenhouse gases (GHG) are the primary driving factor for ET changes, and GHG‐only has already explained ∼78.8% of the observed ET trend. This study for the first time demonstrates that the GHG signal can be detected in the observed‐based ET and can be separable from NAT and aerosol (AER) signals. At the regional scale, CMIP6 simulations work well in North Hemisphere, but are deficient in South Hemisphere. GHG still dominates ET changes in the North Hemisphere, except for Europe, where the influence of AER forcing stands out, and attributable changes to AER is 2.4 times of GHG. Our first quantitative detection and attribution of ET contribute to advance the understanding of anthropogenic activities on hydrological cycle changes.
Smoking-associated upregulation of CBX3 suppresses ARHGAP24 expression to activate Rac1 signaling and promote tumor progression in lung adenocarcinoma
Authors: Jin Xin , Zhang Bin , Zhang Hao , Yu Haixin
Published: November 2021

Although tobacco smoking is a risk factor for lung adenocarcinoma (LUAD), the mechanisms by which tobacco smoking induces LUAD development remain elusive. Histone methylation levels in human bronchial epithelial cells have been reported to increase after exposure to cigarettes. In this study, we explored the mechanisms regulating histone methylation in LUAD in response to smoking. We found that the histone H3K9 methylation reader CBX3 was upregulated in current smokers with LUAD, and that CBX3 overexpression promoted LUAD progression. Functional enrichment analyses revealed that CBX3 regulated the activation of Rho GTPases in LUAD. We also found that by forming a complex with TRIM28, TRIM24, and RBBP4, CBX3 repressed the expression ofARHGAP24and increased the amount of active Rac1 in LUAD cells. Collectively, these results suggest that smoking associated upregulation of CBX3 promotes LUAD progression by activating the ARHGAP24/Rac1 pathway. Hence, the CBX3/ARHGAP24/Rac1 axis may represent a promising therapeutic target in smoking-induced LUAD.
Co-activation of Sonic hedgehog and Wnt signaling in murine retinal precursor cells drives ocular lesions with features of intraocular medulloepithelioma
Authors: Dottermusch Matthias , Sumisławski Piotr , Krevet Julia , Middelkamp Maximilian , Voß Hannah , Siebels Bente , Bartsch Harald , Sotlar Karl , Meyer Peter , Frank Stephan , Korshunov Andrey , Glatzel Markus , Schüller Ulrich , Neumann Julia E.
Published: November 2021

Intraocular medulloepithelioma (IO-MEPL) is a rare embryonal ocular neoplasm, prevalently occurring in children. IO-MEPLs share histomorphological features with CNS embryonal tumors with multilayered rosettes (ETMRs), referred to as intracranial medulloepitheliomas. While Sonic hedgehog (SHH) and WNT signaling pathways are crucial for ETMR pathogenesis, the impact of these pathways on human IO-MEPL development is unclear. Gene expression analyses of human embryonal tumor samples revealed similar gene expression patterns and significant overrepresentation of SHH and WNT target genes in both IO-MEPL and ETMR. In order to unravel the function of Shh and Wnt signaling for IO-MEPL pathogenesis in vivo, both pathways were activated in retinal precursor cells in a time point specific manner. Shh and Wnt co-activation in earlySox2-orRax-expressing precursor cells resulted in infiltrative ocular lesions that displayed extraretinal expansion. Histomorphological, immunohistochemical, and molecular features showed a strong concordance with human IO-MEPL. We demonstrate a relevant role of WNT and SHH signaling in IO-MEPL and report the first mouse model to generate tumor-like lesions with features of IO-MEPL. The presented data may be fundamental for comprehending IO-MEPL initiation and developing targeted therapeutic approaches.
A master of all trades – linking retinoids to different signalling pathways through the multi-purpose receptor STRA6
Authors: Dhokia Vinesh , Macip Salvador
Published: November 2021

Retinoids are a group of vitamin A-related chemicals that are essential to chordate mammals. They regulate a number of basic processes, including embryogenesis and vision. From ingestion to metabolism and the subsequent cellular effects, retinoid levels are tightly regulated in the organism to prevent toxicity. One component of this network, the membrane receptor STRA6, has been shown to be essential in facilitating the cellular entry and exit of retinol. However, recent data suggests that STRA6 may not function merely as a retinoid transporter but also act as a complex signalling hub in its own right, being able to affect cell fate through the integration of retinoid signalling with other key pathways, such as those involving p53, JAK/STAT, Wnt/β catenin and calcium. This may open new therapeutic strategies in diseases like cancer, where these pathways are often compromised. Here, we look at the growing evidence regarding the novel roles of STRA6 beyond its well characterized classic functions.
Programmable viscoelasticity in protein-RNA condensates with disordered sticker-spacer polypeptides
Authors: Alshareedah Ibraheem , Moosa Mahdi Muhammad , Pham Matthew , Potoyan Davit A. , Banerjee Priya R.
Published: November 2021

Liquid-liquid phase separation of multivalent proteins and RNAs drives the formation of biomolecular condensates that facilitate membrane-free compartmentalization of subcellular processes. With recent advances, it is becoming increasingly clear that biomolecular condensates are network fluids with time-dependent material properties. Here, employing microrheology with optical tweezers, we reveal molecular determinants that govern the viscoelastic behavior of condensates formed by multivalent Arg/Gly-rich sticker-spacer polypeptides and RNA. These condensates behave as Maxwell fluids with an elastically-dominant rheological response at shorter timescales and a liquid-like behavior at longer timescales. The viscous and elastic regimes of these condensates can be tuned by the polypeptide and RNA sequences as well as their mixture compositions. Our results establish a quantitative link between the sequence- and structure-encoded biomolecular interactions at the microscopic scale and the rheological properties of the resulting condensates at the mesoscale, enabling a route to systematically probe and rationally engineer biomolecular condensates with programmable mechanics.
SARS-CoV-2 infection and replication in human gastric organoids
Authors: Giobbe Giovanni Giuseppe , Bonfante Francesco , Jones Brendan C. , Gagliano Onelia , Luni Camilla , Zambaiti Elisa , Perin Silvia , Laterza Cecilia , Busslinger Georg , Stuart Hannah , Pagliari Matteo , Bortolami Alessio , Mazzetto Eva , Manfredi Anna , Colantuono Chiara , Di Filippo Lucio , Pellegata Alessandro Filippo , Panzarin Valentina , Thapar Nikhil , Li Vivian Sze Wing , Eaton Simon , Cacchiarelli Davide , Clevers Hans , Elvassore Nicola , De Coppi Paolo
Published: November 2021

COVID-19 typically manifests as a respiratory illness, but several clinical reports have described gastrointestinal symptoms. This is particularly true in children in whom gastrointestinal symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. These observations raise the question of whether the virus can replicate within the stomach. Here we generate gastric organoids from fetal, pediatric, and adult biopsies as in vitro models of SARS-CoV-2 infection. To facilitate infection, we induce reverse polarity in the gastric organoids. We find that the pediatric and late fetal gastric organoids are susceptible to infection with SARS-CoV-2, while viral replication is significantly lower in undifferentiated organoids of early fetal and adult origin. We demonstrate that adult gastric organoids are more susceptible to infection following differentiation. We perform transcriptomic analysis to reveal a moderate innate antiviral response and a lack of differentially expressed genes belonging to the interferon family. Collectively, we show that the virus can efficiently infect the gastric epithelium, suggesting that the stomach might have an active role in fecal-oral SARS-CoV-2 transmission.
Simultaneous functional MRI of two awake marmosets
Authors: Gilbert Kyle M. , Cléry Justine C. , Gati Joseph S. , Hori Yuki , Johnston Kevin D. , Mashkovtsev Alexander , Selvanayagam Janahan , Zeman Peter , Menon Ravi S. , Schaeffer David J. , Everling Stefan
Published: November 2021

Social cognition is a dynamic process that requires the perception and integration of a complex set of idiosyncratic features between interacting conspecifics. Here we present a method for simultaneously measuring the whole-brain activation of two socially interacting marmoset monkeys using functional magnetic resonance imaging. MRI hardware (a radiofrequency coil and peripheral devices) and image-processing pipelines were developed to assess brain responses to socialization, both on an intra-brain and inter-brain level. Notably, the brain activation of a marmoset when viewing a second marmoset in-person versus when viewing a pre-recorded video of the same marmoset—i.e., when either capable or incapable of socially interacting with a visible conspecific—demonstrates increased activation in the face-patch network. This method enables a wide range of possibilities for potentially studying social function and dysfunction in a non-human primate model.
Hydrogen peroxide signaling via its transformation to a stereospecific alkyl hydroperoxide that escapes reductive inactivation
Authors: Queiroz Raphael F. , Stanley Christopher P. , Wolhuter Kathryn , Kong Stephanie M. Y. , Rajivan Ragul , McKinnon Naomi , Nguyen Giang T. H. , Roveri Antonella , Guttzeit Sebastian , Eaton Philip , Donald William A. , Ursini Fulvio , Winterbourn Christine C. , Ayer Anita , Stocker Roland
Published: November 2021

During systemic inflammation, indoleamine 2,3-dioxygenase 1 (IDO1) becomes expressed in endothelial cells where it uses hydrogen peroxide (H2O2) to oxidize L-tryptophan to the tricyclic hydroperoxide, cis-WOOH, that then relaxes arteries via oxidation of protein kinase G 1α. Here we show that arterial glutathione peroxidases and peroxiredoxins that rapidly eliminate H2O2, have little impact on relaxation of IDO1-expressing arteries, and that purified IDO1 forms cis-WOOH in the presence of peroxiredoxin 2. cis-WOOH oxidizes protein thiols in a selective and stereospecific manner. Compared with its epimer trans-WOOH and H2O2, cis-WOOH reacts slower with the major arterial forms of glutathione peroxidases and peroxiredoxins while it reacts more readily with its target, protein kinase G 1α. Our results indicate a paradigm of redox signaling by H2O2 via its enzymatic conversion to an amino acid-derived hydroperoxide that ‘escapes’ effective reductive inactivation to engage in selective oxidative activation of key target proteins.
The impact of muscle mass loss and deteriorating physical function on prognosis in patients receiving hemodialysis
Authors: Kitamura Mineaki , Takazono Takahiro , Yamaguchi Kosei , Notomi Satoko , Sawase Kenji , Harada Takashi , Funakoshi Satoshi , Mukae Hiroshi , Nishino Tomoya
Published: November 2021

Muscle mass loss and worsening physical function are crucial issues in patients receiving hemodialysis (HD). However, few studies have investigated the association between temporal changes in muscle mass and physical function in a large number of HD patients. We examined 286 patients receiving HD (males, 58%; age, 66.8 ± 13.0 years) at a single center, and calculated the percent changes in psoas muscle mass index (%PMI) using computed tomography over two screenings, once per year (July 2011–June 2013). Physical function was evaluated using the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (range 0–4). The observation period was from July 2012 to June 2021. The median %PMI was -9.5%, and those with the lowest quartile of %PMI (< −20.5%) showed a significantly poor prognosis compared with other patients (p < 0.001). Multivariable logistic regression analysis revealed that these patients tended to have decreased physical function (ECOG-PS 2–4) [odds ratio (OR): 2.46, p < 0.001] and albumin levels (OR: 0.22, p = 0.007). Multiple-factor-adjusted Cox regression analyses showed that %PMI (hazard ratio: 0.99, p = 0.004) and each ECOG-PS stage (1–4 vs. 0) (p < 0.01) were associated with mortality. Augmenting physical activities in daily life and serum albumin levels should be considered to maintain muscle mass and improve the prognosis of patients receiving HD.
Enhancing diversity analysis by repeatedly rarefying next generation sequencing data describing microbial communities
Authors: Cameron Ellen S. , Schmidt Philip J. , Tremblay Benjamin J.-M. , Emelko Monica B. , Müller Kirsten M.
Published: November 2021

Amplicon sequencing has revolutionized our ability to study DNA collected from environmental samples by providing a rapid and sensitive technique for microbial community analysis that eliminates the challenges associated with lab cultivation and taxonomic identification through microscopy. In water resources management, it can be especially useful to evaluate ecosystem shifts in response to natural and anthropogenic landscape disturbances to signal potential water quality concerns, such as the detection of toxic cyanobacteria or pathogenic bacteria. Amplicon sequencing data consist of discrete counts of sequence reads, the sum of which is the library size. Groups of samples typically have different library sizes that are not representative of biological variation; library size normalization is required to meaningfully compare diversity between them. Rarefaction is a widely used normalization technique that involves the random subsampling of sequences from the initial sample library to a selected normalized library size. This process is often dismissed as statistically invalid because subsampling effectively discards a portion of the observed sequences, yet it remains prevalent in practice and the suitability of rarefying, relative to many other normalization approaches, for diversity analysis has been argued. Here, repeated rarefying is proposed as a tool to normalize library sizes for diversity analyses. This enables (i) proportionate representation of all observed sequences and (ii) characterization of the random variation introduced to diversity analyses by rarefying to a smaller library size shared by all samples. While many deterministic data transformations are not tailored to produce equal library sizes, repeatedly rarefying reflects the probabilistic process by which amplicon sequencing data are obtained as a representation of the amplified source microbial community. Specifically, it evaluates which data might have been obtained if a particular sample’s library size had been smaller and allows graphical representation of the effects of this library size normalization process upon diversity analysis results.
Mid-gestation cytokine profiles in mothers of children affected by autism spectrum disorder: a case–control study
Authors: Carter Michael , Casey Sophie , O’Keeffe Gerard W. , Gibson Louise , Murray Deirdre M.
Published: November 2021

Autism Spectrum disorder is one of the commonest and most important neurodevelopmental conditions affecting children today. With an increasing prevalence and an unclear aetiology, it is imperative we find early markers of autism, which may facilitate early identification and intervention. Alterations of gestational cytokine profiles have been reported in mothers of autistic children. Increasing evidence suggests that the intrauterine environment is an important determinant of autism risk. This study aims to examine the mid-gestational serum cytokine profiles of the mothers of autistic children from a well-characterised birth cohort. A nested sub-cohort within a large mother–child birth cohort were identified based on a confirmed multi-disciplinary diagnosis of autism before the age 10 years and neuro-typical matched controls in a 2:1 ratio. IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-17A, GMCSF and TNFα were measured in archived maternal 20-week serum using MesoScale Diagnostics multiplex technology and validation of our IL-17A measurements was performed using an ultrasensitive assay. From a cohort of 2137 children, 25 had confirmed autism before 10 years and stored maternal serum from mid-gestation. We examined the sera of these 25 cases and 50 matched controls. The sex ratio was 4:1 males to females in each group, and the mean age at diagnosis was 5.09 years (SD 2.13). We found that concentrations of IL-4 were significantly altered between groups. The other analytes did not differ significantly using either multiplex or ultra-sensitive assays. In our well-characterised prospective cohort of autistic children, we confirmed mid-gestational alterations in maternal IL-4 concentrations in autism affected pregnancies versus matched controls. These findings add to promising evidence from animal models and retrospective screening programmes and adds to the knowledge in this field.
EEG and behavioral correlates of attentional processing while walking and navigating naturalistic environments
Authors: Liebherr Magnus , Corcoran Andrew W. , Alday Phillip M. , Coussens Scott , Bellan Valeria , Howlett Caitlin A. , Immink Maarten A. , Kohler Mark , Schlesewsky Matthias , Bornkessel-Schlesewsky Ina
Published: November 2021

The capacity to regulate one’s attention in accordance with fluctuating task demands and environmental contexts is an essential feature of adaptive behavior. Although the electrophysiological correlates of attentional processing have been extensively studied in the laboratory, relatively little is known about the way they unfold under more variable, ecologically-valid conditions. Accordingly, this study employed a ‘real-world’ EEG design to investigate how attentional processing varies under increasing cognitive, motor, and environmental demands. Forty-four participants were exposed to an auditory oddball task while (1) sitting in a quiet room inside the lab, (2) walking around a sports field, and (3) wayfinding across a university campus. In each condition, participants were instructed to either count or ignore oddball stimuli. While behavioral performance was similar across the lab and field conditions, oddball count accuracy was significantly reduced in the campus condition. Moreover, event-related potential components (mismatch negativity and P3) elicited in both ‘real-world’ settings differed significantly from those obtained under laboratory conditions. These findings demonstrate the impact of environmental factors on attentional processing during simultaneously-performed motor and cognitive tasks, highlighting the value of incorporating dynamic and unpredictable contexts within naturalistic designs.
An innovative approach for provenancing ancient white marbles: the contribution of x-ray diffraction to disentangling the origins of Göktepe and Carrara marbles
Authors: Antonelli F. , Nestola F.
Published: November 2021

The paper presents a very efficient, quick, low-cost and minimally micro-destructive approach to discriminating between Roman artefacts sculpted with Göktepe (Aphrodisia, Turkey) or Carrara (Apuan Alps, Italy) white marbles by using a standard X-Ray Powder Diffractometer (XRPD) and a refinement of the unit cell parameters and volume of calcite. At present, the routine way of differentiating between these two almost indistinguishable by-eye marbles is based on the typically higher strontium content of calcite in the Microasiatic lithotype, a unique geochemical-crystallographic feature with respect to all other non-Göktepe fine-grained white marbles used in classical times. The XRPD approach has been verified by testing eighteen samples of known composition, nine from Carrara and nine from Göktepe quarries, which had already been analysed with other laboratory techniques. The applicability of the method to archaeological artefacts was confirmed by an archaeometric study performed on some famous Roman sculptures of the National Archaeological Museum of Venice and from Hadrian’s Villa at Tivoli. The results show that Göktepe/Carrara discrimination is always possible and that this XRPD approach can potentially become a useful and low-cost routine procedure to solve provenance issues.
Effect of biostimulants on the growth, yield and nutritional value of Capsicum annuum grown in an unheated plastic tunnel
Authors: Majkowska-Gadomska Joanna , Dobrowolski Artur , Jadwisieńczak Krzysztof K. , Kaliniewicz Zdzisław , Francke Anna
Published: November 2021

Recent years have witnessed an increased interest in the cultivation and consumption of peppers. Therefore, new solutions are being sought to provide pepper plants with the most favorable conditions for growth and development. In view of the above, the aim of this study was to evaluate the effect of selected biostimulants on the biometric parameters, yield and nutritional value of Capsicum annuum fruit. The research hypothesis postulates that biostimulants can increase the yield and improve the nutritional quality of pepper fruit. The experiment was conducted in an unheated plastic tunnel. The experimental materials comprised three sweet (‘Solario F1’, ‘Turbine F1’ and ‘Whitney F1’) and two hot (‘Cyklon’ and ‘Palivec’) cultivars of C. annuum. It was found that the combined application of environmentally-friendly microbial-based biostimulants (BB Soil, BB Foliar, Multical, MK5 and Biocin F) did not clearly improve the morphological traits of pepper fruit, yield or the concentrations of sugars and organic acids in fruit, therefore their use is not economically justified. Hot peppers had a higher content of dry matter, total sugars and L-ascorbic acid than sweet peppers. The analyzed biostimulants increased nitrate (V) concentrations in the fruit of both hot and sweet peppers. ‘Turbine F1’ and ‘Solario F1’ were particularly prone to nitrate (V) accumulation in fruit, therefore the use of biostimulants should be limited in their cultivation. Pepper fruits with the largest horizontal diameter and the thickest skin should be preferred because these traits are associated with high sugar content.