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Abstract Humans perceive illusory faces in everyday objects with a face-like configuration, an illusion known as face pareidolia. Face-selective regions in humans and monkeys, believed to underlie face perception, have been shown to respond to face pareidolia images. Here, we investigated whether pareidolia selectivity in macaque inferotemporal cortex is explained by the face-like configuration that drives the human perception of illusory faces. We found that face cells responded selectively to pareidolia images. This selectivity did not correlate with human faceness ratings and did not require the face-like configuration. Instead, it was driven primarily by the “eye” parts of the illusory face, which are simply object parts when viewed in isolation. In contrast, human perceptual pareidolia relied primarily on the global configuration and could not be explained by “eye” parts. Our results indicate that face-cells encode local, generic features of illusory faces, in misalignment with human visual perception, which requires holistic information.

Currently, information on the toxicity profile of the majority of the identified e‐waste chemicals, while extensive and growing, is admittedly fragmentary, particularly at the cellular and molecular levels. Furthermore, the toxicity of the chemical mixtures likely to be encountered by humans during and after informal e‐waste recycling, as well as their underlying mechanisms of action, is largely unknown. This review paper summarizes state‐of‐the‐art knowledge of the potential underlying toxicity mechanisms associated with e‐waste exposures, with a focus on toxic responses connected to specific organs, organ systems, and overall effects on the organism. To overcome the complexities associated with assessing the possible adverse outcomes from exposure to chemicals, a growing number of new approach methodologies have emerged in recent years, with the long‐term objective of providing a human‐based and animal‐free system that is scientifically superior to animal testing, more effective, and acceptable. This encompasses a variety of techniques, typically regarded as alternative approaches for determining chemical‐induced toxicities and holds greater promise for a better understanding of key events in the metabolic pathways that mediate known adverse health outcomes in e‐waste exposure scenarios. This is crucial to establishing accurate scientific knowledge on mixed e‐waste chemical exposures in shorter time frames and with greater efficacy, as well as supporting the need for safe management of hazardous chemicals. The present review paper discusses important gaps in knowledge and shows promising directions for mechanistically anchored effect‐based monitoring strategies that will contribute to the advancement of the methods currently used in characterizing and monitoring e‐waste‐impacted ecosystems.

Specific aesthetic features of the object and observer's expertise seem to be related to the perception of motion aesthetics. How differing kinematic motion characteristics and their manifestation are related to the perception of motion aesthetics and how this relates to the observer's expertise is still investigated. It is hypothesized that different manifestations of the kinematic motion characteristics amplitude, fluency, and complexity are related to perceived motion aesthetics of dance skills and observer's expertise. Dancers' and non-dancers' perception of motion aesthetics was assessed when watching stick-figure video sequences of semi-standardized dance jumps, classified relating to three kinematic motion characteristics and their semantic differentials. Large, fluent, and complex dance jumps were perceived as more aesthetic than small, jerky, and simple jumps. There was no general effect on the observer's expertise. Nevertheless, non-dancers gave higher aesthetic ratings for complex dance jumps than dancers. Findings indicate that expertise does not relate to the perception of motion aesthetics per se. In contrast, specific kinematic motion characteristics of dance jumps do. Amplitude and fluency seem to be remarkable objective aesthetic qualities when perceiving motion aesthetics of dance skills. The observed dance skills' complexity appears to be a critical parameter when addressing observers with different expertise.

Objectives: Elastic taping is postulated to support musculoskeletal aspects of athletic performance. Thereby, specific application techniques should affect specific aspects of muscle functioning, thus facilitating or inhibiting tonicity of the taped muscle. This study examines if different application directions of elastic taping on the quadriceps femoris muscle affect vertical jump performance. Additionally, participants subjective sensation during such facilitative and inhibitory elastic tapings is investigated.Methods: 30 participants were asked to perform counter movement jumps without, with facilitative, and with inhibitory elastic taping. Tape application conditions were presented randomly. Participants were blinded concerning postulated effects and application techniques. Height of flight during counter movement jumps was measured to indicate vertical jump performance. Vertical jumps were captured with a high-speed camera. Subjective sensation was investigated using an eleven-point Likert-scale (-5=strongly impaired, 0=neither nor, +5=strongly supported) and participants were asked to evaluate elastic tape applications with regard to jump performance and overall leg sensation. Results: Both elastic tape applications impair jump performance. However, participants evaluate both applications as supportive. There is no difference between facilitative and inhibitory tape application techniques.Discussion: Hypothesized performance-enhancing effects of elastic taping on jump performance in active, healthy and young participants can be neglected. However, elastic tape applications affect participants subjective sensation, which should be considered depending on given context and intention KEY WORDS: Kinesiotaping, Counter Movement Jump, Athletic Performance, Videoanalysis, Likert-Scale

The provided dataset describes the transcriptomic profile of human liver spheroid co-cultures consisting of a human hepatoma cell line (C3A/HepG2 cells) and an immortalized activated human hepatic stellate cell line (LX-2 cells) upon exposure to total parenteral nutrition. High-throughput RNA sequencing was performed using DNBSEQTM sequencing technology. Following the quality check and filtering of raw sequence reads, the clean reads were aligned to the reference human genome and used to determine differential gene expression. Raw and processed data are deposited in the Gene Expression Omnibus with accession number GSE264357. These data could serve further mechanistic studies on parenteral nutrition-induced liver injury and support translational research on intestinal failure-associated liver disease occurring in individuals receiving total parenteral nutrition.

To study the ways in which compounds can induce adverse effects, toxicologists have been constructing Adverse Outcome Pathways (AOPs). An AOP can be considered as a pragmatic tool to capture and visualize mechanisms underlying different types of toxicity inflicted by any kind of stressor, and describes the interactions between key entities that lead to the adverse outcome on multiple biological levels of organization. The construction or optimization of an AOP is a labor intensive process, which currently depends on the manual search, collection, reviewing and synthesis of available scientific literature. This process could however be largely facilitated using Natural Language Processing (NLP) to extract information contained in scientific literature in a systematic, objective, and rapid manner that would lead to greater accuracy and reproducibility. This would support researchers to invest their expertise in the substantive assessment of the AOPs by replacing the time spent on evidence gathering by a critical review of the data extracted by NLP. As case examples, we selected two frequent adversities observed in the liver: namely, cholestasis and steatosis denoting accumulation of bile and lipid, respectively. We used deep learning language models to recognize entities of interest in text and establish causal relationships between them. We demonstrate how an NLP pipeline combining Named Entity Recognition and a simple rules-based relationship extraction model helps screen compounds related to liver adversities in the literature, but also extract mechanistic information for how such adversities develop, from the molecular to the organismal level. Finally, we provide some perspectives opened by the recent progress in Large Language Models and how these could be used in the future. We propose this work brings two main contributions: 1) a proof-of-concept that NLP can support the extraction of information from text for modern toxicology and 2) a template open-source model for recognition of toxicological entities and extraction of their relationships. All resources are openly accessible via GitHub (https://github.com/ontox-project/en-tox).

Background: Serum transaminases, alkaline phosphatase and bilirubin are common parameters used for DILI diagnosis, classification, and prognosis. However, the relevance of clinical examination, histopathology and drug chemical properties have not been fully investigated. As cholestasis is a frequent and complex DILI manifestation, our goal was to investigate the relevance of clinical features and drug properties to stratify drug-induced cholestasis (DIC) patients, and to develop a prognosis model to identify patients at risk and high-concern drugs. Methods: DIC-related articles were searched by keywords and Boolean operators in seven databases. Relevant articles were uploaded onto Sysrev, a machine-learning based platform for article review and data extraction. Demographic, clinical, biochemical, and liver histopathological data were collected. Drug properties were obtained from databases or QSAR modelling. Statistical analyses and logistic regressions were performed. Results: Data from 432 DIC patients associated with 52 drugs were collected. Fibrosis strongly associated with fatality, whereas canalicular paucity and ALP associated with chronicity. Drugs causing cholestasis clustered in three major groups. The pure cholestatic pattern divided into two subphenotypes with differences in prognosis, canalicular paucity, fibrosis, ALP and bilirubin. A predictive model of DIC outcome based on non-invasive parameters and drug properties was developed. Results demonstrate that physicochemical (pKa-a) and pharmacokinetic (bioavailability, CYP2C9) attributes impinged on the DIC phenotype and allowed the identification of high-concern drugs. Conclusions: We identified novel associations among DIC manifestations and disclosed novel DIC subphenotypes with specific clinical and chemical traits. The developed predictive DIC outcome model could facilitate DIC prognosis in clinical practice and drug categorization.

On 26th February 2024, in its Giudizio Universale decision, the Tribunal of Rome penned the first Italian climate judgement. Shortly after, on 9 April 2024, the ECtHR handed down its seminal trio of KlimaSeniorinnen v. Switzerland, Duarte Agostinho v. Portugal and Others and Carême v. France. In this monumental string of cases, the ECtHR set the new standard for climate litigation in Europe, also regarding separation of powers. This invites a critical assessment of Giudizio Universale’s stance.

Abstract Background The opening of pannexin1 channels is considered as a key event in inflammation. Pannexin1 channel-mediated release of adenosine triphosphate triggers inflammasome signaling and activation of immune cells. By doing so, pannexin1 channels play an important role in several inflammatory diseases. Although pannexin1 channel inhibition could represent a novel clinical strategy for treatment of inflammatory disorders, therapeutic pannexin1 channel targeting is impeded by the lack of specific, potent and/or in vivo-applicable inhibitors. The goal of this study is to generate nanobody-based inhibitors of pannexin1 channels. Results Pannexin1-targeting nanobodies were developed as potential new pannexin1 channel inhibitors. We identified 3 cross-reactive nanobodies that showed affinity for both murine and human pannexin1 proteins. Flow cytometry experiments revealed binding capacities in the nanomolar range. Moreover, the pannexin1-targeting nanobodies were found to block pannexin1 channel-mediated release of adenosine triphosphate. The pannexin1-targeting nanobodies were also demonstrated to display anti-inflammatory effects in vitro through reduction of interleukin 1 beta amounts. This anti-inflammatory outcome was reproduced in vivo using a human-relevant mouse model of acute liver disease relying on acetaminophen overdosing. More specifically, the pannexin1-targeting nanobodies lowered serum levels of inflammatory cytokines and diminished liver damage. These effects were linked with alteration of the expression of several NLRP3 inflammasome components. Conclusions This study introduced for the first time specific, potent and in vivo-applicable nanobody-based inhibitors of pannexin1 channels. As demonstrated for the case of liver disease, the pannexin1-targeting nanobodies hold great promise as anti-inflammatory agents, yet this should be further tested for extrahepatic inflammatory disorders. Moreover, the pannexin1-targeting nanobodies represent novel tools for fundamental research regarding the role of pannexin1 channels in pathological and physiological processes. Graphical Abstract

This article makes three arguments to contribute to this thematic issue’s intention of examining the role of public spheres in global politics. To begin with, it attempts to develop the concept of “strong” public spheres to include plenary organs of international institutions. It believes in the potential of this concept as a heuristic fiction. The study then examines the role of international law in shaping global public spheres and their role in global politics. International law’s characteristics have contributed to the current incomplete manifestations of global publics. Not only has international law constructed the institutional frameworks of the “strong” public sphere within international institutions, but it has also integrated civil society actors into the deliberative processes of will formation of these institutions. Finally, this research turns to international climate change law as a case study. The institutional structures created by international climate change law have not only created one “strong” public sphere in the form of the conference of the parties but rely on a second “strong” global public, the Intergovernmental Panel on Climate Change, which aims to institutionalise the global climate science community without abandoning an intergovernmental structure. What is more, the paradigm shift accompanying the Paris Agreement has made global climate change governance increasingly reliant on an active transnational global public sphere.

Many species are able to recognize objects, but it has been proven difficult to pinpoint and compare how different species solve this task. Recent research suggested to combine computational and animal modelling in order to obtain a more systematic understanding of task complexity and compare strategies between species. In this study, we created a large multidimensional stimulus set and designed a visual discrimination task partially based upon modelling with a convolutional deep neural network (CNN). Experiments included rats (N = 11; 1115 daily sessions in total for all rats together) and humans (N = 45). Each species was able to master the task and generalize to a variety of new images. Nevertheless, rats and humans showed very little convergence in terms of which object pairs were associated with high and low performance, suggesting the use of different strategies. There was an interaction between species and whether stimulus pairs favoured early or late processing in a CNN. A direct comparison with CNN representations and visual feature analyses revealed that rat performance was best captured by late convolutional layers and partially by visual features such as brightness and pixel-level similarity, while human performance related more to the higher-up fully connected layers. These findings highlight the additional value of using a computational approach for the design of object recognition tasks. Overall, this computationally informed investigation of object recognition behaviour reveals a strong discrepancy in strategies between rodent and human vision.

Background and aimsObservational data indicate that diets rich in fruits and vegetables have a positive effect on inflammatory status, improve metabolic resilience and may protect against the development of non-communicable diseases. Nevertheless, experimental evidence demonstrating a causal relationship between nutrient intake (especially whole foods) and changes in metabolic health is scarce. This study investigated the pleiotropic effects of sulforaphane from broccoli sprouts, compared to pea sprouts, on biomarkers of endothelial function, inflammation and metabolic stress in healthy participants subjected to a standardized caloric challenge.MethodsIn this double-blind, crossover, randomized, placebo-controlled trial 12 healthy participants were administered 16 g broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to disturb healthy homeostasis. Levels of inflammatory biomarkers and metabolic parameters were measured in plasma before and 2 h after the caloric overload.ResultsAdministration of broccoli sprouts promoted an increase in levels of CCL-2 induced by caloric load (p = 0.017). Other biomarkers (sICAM-1, sVCAM-1, hs-CRP, and IL-10) individually showed insignificant tendencies toward increase with administration of sulforaphane. Combining all studied biomarkers into the systemic low-grade inflammation score further confirmed upregulation of the inflammatory activity (p = 0.087) after sulforaphane. No significant effects on biomarkers of metabolic stress were detected.ConclusionThis study has demonstrated that sulforaphane facilitated development of a mild pro-inflammatory state during the caloric challenge, which could be suggestive of the onset of the hormetic response induced by this phytonutrient. The use of integrative outcomes measures such as the systemic low-grade inflammation score can be viewed as a more robust approach to study the subtle and pleiotropic effects of phytonutrients.Clinical trial registration:www.clinicaltrials.gov, identifier NCT05146804.

Cell junctions, including anchoring, occluding and communicating junctions, play an indispensable role in tissue architecture and homeostasis. Consequently, malfunctioning of cell junctions is linked with a wide range of disorders, including in liver. The present study was set up to investigate the effects of acute and chronic disease induced by chemical compounds on hepatic cell junctions in mice. Mice were either overdosed with paracetamol or repeatedly administered carbon tetrachloride followed by sampling at 24 hours or 8 weeks, respectively. mRNA and protein expression levels of adherens, gap and tight junction components were measured in liver using reverse transcription quantitative real-time polymerase chain reaction analysis and immunoblot techniques, respectively. It was found that protein levels of the adherens junction building blocks β-catenin and γ-catenin, the gap junction components Cx26 and Cx32, and the tight junction constituent zonula occludens 2 were decreased, while mRNA levels of the adherens junction building block E-cadherin, and the tight junction constituent zonula occludens 2 and claudin 1 were upregulated following paracetamol overdosing. Repeated administration of carbon tetrachloride increased protein levels of E-cadherin, β-catenin, Cx26, Cx32, Cx43 and claudin 1. The latter was reflected at the mRNA level. In conclusion, acute and chronic liver disease have different effects on cell junctions in liver.

Abstract Models of object recognition have mostly focused upon the hierarchical processing of objects from local edges up to more complex shape features. An alternative strategy that might be involved in pattern recognition centres around coarse-level contrast features. In humans and monkeys, the use of such features is most documented in the domain of face perception. Given prior suggestions that, generally, rodents might rely upon contrast features for object recognition, we hypothesized that they would pick up the typical contrast features relevant for face detection. We trained rats in a face-nonface categorization task with stimuli previously used in computer vision and tested for generalization with new, unseen stimuli by including manipulations of the presence and strength of a range of contrast features previously identified to be relevant for face detection. Although overall generalization performance was low, it was significantly modulated by contrast features. A model taking into account the summed strength of contrast features predicted the variation in accuracy across stimuli. Finally, with deep neural networks, we further investigated and quantified the performance and representations of the animals. The findings suggest that rat behaviour in visual pattern recognition tasks is partially explained by contrast feature processing.

The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk assessment and ethics of this system, demanding a change of paradigm. At the same time, the scientific toolbox used for risk assessment is continuously enriched by the development of “New Approach Methodologies” (NAMs). While this term does not define the age or the state of readiness of the innovation, it covers a wide range of methods, including quantitative structure–activity relationship (QSAR) predictions, high-throughput screening (HTS) bioassays, omics applications, cell cultures, organoids, microphysiological systems (MPS), machine learning models and artificial intelligence (AI). In addition to promising faster and more efficient toxicity testing, NAMs have the potential to fundamentally transform today’s regulatory work by allowing more human-relevant decision-making in terms of both hazard and exposure assessment. Yet, several obstacles hamper a broader application of NAMs in current regulatory risk assessment. Constraints in addressing repeated-dose toxicity, with particular reference to the chronic toxicity, and hesitance from relevant stakeholders, are major challenges for the implementation of NAMs in a broader context. Moreover, issues regarding predictivity, reproducibility and quantification need to be addressed and regulatory and legislative frameworks need to be adapted to NAMs. The conceptual perspective presented here has its focus on hazard assessment and is grounded on the main findings and conclusions from a symposium and workshop held in Berlin in November 2021. It intends to provide further insights into how NAMs can be gradually integrated into chemical risk assessment aimed at protection of human health, until eventually the current paradigm is replaced by an animal-free “Next Generation Risk Assessment” (NGRA).

Pannexin1 proteins form communication channels at the cell plasma membrane surface, which allow the transfer of small molecules and ions between the intracellular compartment and extracellular environment. In this way, pannexin1 channels play an important role in various cellular processes and diseases. Indeed, a plethora of human pathologies is associated with the activation of pannexin1 channels. The present paper reviews and summarizes the structure, life cycle, regulation and (patho)physiological roles of pannexin1 channels, with a particular focus on the relevance of pannexin1 channels in liver diseases.

Connexin proteins can form hexameric hemichannels and gap junctions that mediate paracrine and direct intercellular communication, respectively. Gap junction activity is crucial for the maintenance of hepatic homeostasis, while connexin hemichannels become particularly active in liver disease, such as hepatitis, fibrosis, cholestasis or even hepatocellular carcinoma. Channels consisting of connexin-like proteins named pannexins have been directly linked to liver inflammation and cell death. The goal of the present study was to characterize the expression and subcellular localization of connexins and pannexins in liver of patients suffering from various chronic and neoplastic liver diseases. Specifically, real-time quantitative reverse transcription polymerase chain reaction, immunoblotting and immunohistochemistry analyses were performed on human liver biopsies. It was found that pannexin1 and pannexin2 gene expression are correlated to a certain degree, as is pannexin1 protein expression with connexin32 and connexin43 protein expression. Furthermore, this study is the first to detect pannexin3 in human patient liver biopsies via both immunoblot and immunohistochemistry.

The recently concluded Agreement on the Conservation and Sustainable Use of Marine Biological Diversity of Areas Beyond National Jurisdiction has been described as the ‚New York Moment‘ for the oceans, to join the ‚Paris Moment‘ for the climate. The Paris Agreement was considered to be such a moment, in part, because it constituted a significant paradigm shift in international environmental law, institutionally as well as substantively. The current draft of the BBNJ arguably contains a paradigm shift of comparable significance for the law of the sea in at least three respects.

Currently, information on the toxicity profile of the majority of the identified e‐waste chemicals, while extensive and growing, is admittedly fragmentary, particularly at the cellular and molecular levels. Furthermore, the toxicity of the chemical mixtures likely to be encountered by humans during and after informal e‐waste recycling, as well as their underlying mechanisms of action, is largely unknown. This review paper summarizes state‐of‐the‐art knowledge of the potential underlying toxicity mechanisms associated with e‐waste exposures, with a focus on toxic responses connected to specific organs, organ systems, and overall effects on the organism. To overcome the complexities associated with assessing the possible adverse outcomes from exposure to chemicals, a growing number of new approach methodologies have emerged in recent years, with the long‐term objective of providing a human‐based and animal‐free system that is scientifically superior to animal testing, more effective, and acceptable. This encompasses a variety of techniques, typically regarded as alternative approaches for determining chemical‐induced toxicities and holds greater promise for a better understanding of key events in the metabolic pathways that mediate known adverse health outcomes in e‐waste exposure scenarios. This is crucial to establishing accurate scientific knowledge on mixed e‐waste chemical exposures in shorter time frames and with greater efficacy, as well as supporting the need for safe management of hazardous chemicals. The present review paper discusses important gaps in knowledge and shows promising directions for mechanistically anchored effect‐based monitoring strategies that will contribute to the advancement of the methods currently used in characterizing and monitoring e‐waste‐impacted ecosystems. [ABSTRACT FROM AUTHOR]

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a very rare but serious adverse reaction that can occur after Ad26.COV2.S vaccination in humans, leading to thrombosis at unusual anatomic sites. One hypothesis is that accidental intravenous (IV) administration of Ad26.COV2.S or drainage of the vaccine from the muscle into the circulatory system may result in interaction of the vaccine with blood factors associated with platelet activation, leading to VITT. Here, we demonstrate that, similar to intramuscular (IM) administration of Ad26.COV2.S in rabbits, IV dosing was well tolerated, with no significant differences between dosing routes for the assessed hematologic, coagulation time, innate immune, or clinical chemistry parameters and no histopathologic indication of thrombotic events. For both routes, all other non-adverse findings observed were consistent with a normal vaccine response and comparable to those observed for unrelated or other Ad26-based control vaccines. However, Ad26.COV2.S induced significantly higher levels of C-reactive protein on day 1 after IM vaccination compared with an Ad26-based control vaccine encoding a different transgene, suggesting an inflammatory effect of the vaccine-encoded spike protein. Although based on a limited number of animals, these data indicate that an accidental IV injection of Ad26.COV2.S may not represent an increased risk for VITT.

Identifying cognitive capacities underlying the human evolutionary transition is challenging, and many hypotheses exist for what makes humans capable of, for example, producing and understanding language, preparing meals, and having culture on a grand scale. Instead of describing processes whereby information is processed, recent studies have suggested that there are key differences between humans and other animals in how information is recognized and remembered. Such constraints may act as a bottleneck for subsequent information processing and behavior, proving important for understanding differences between humans and other animals. We briefly discuss different sequential aspects of cognition and behavior and the importance of distinguishing between simultaneous and sequential input, and conclude that explicit tests on non-human great apes have been lacking. Here, we test the memory for stimulus sequences-hypothesis by carrying out three tests on bonobos and one test on humans. Our results show that bonobos' general working memory decays rapidly and that they fail to learn the difference between the order of two stimuli even after more than 2,000 trials, corroborating earlier findings in other animals. However, as expected, humans solve the same sequence discrimination almost immediately. The explicit test on whether bonobos represent stimulus sequences as an unstructured collection of memory traces was not informative as no differences were found between responses to the different probe tests. However, overall, this first empirical study of sequence discrimination on non-human great apes supports the idea that non-human animals, including the closest relatives to humans, lack a memory for stimulus sequences. This may be an ability that sets humans apart from other animals and could be one reason behind the origin of human culture.

Understanding stability of representation in the visual system can benefit by use of non-static, naturalistic stimuli. Here the authors examine stability of neural representations along the rat ventral stream while viewing naturalistic and synthetic movies.

The perception of (motion) aesthetics is related to the circumstances of the object, the observer, and the given context. The central question of this study is whether the perception of motion aesthetics is related to a motor skill’s ratio of flight kinematics and the observer’s sensory-motor experiences. Motor skills, perceived as more aesthetic, are hypothesized to show kinematic flight ratios near the golden ratio. Motor skills, perceived as less aesthetic, are hypothesized to show kinematic flight ratios farther away from the golden ratio. Furthermore, this relationship is hypothesized to be related to the observer’s sensory-motor experience. Therefore, 36 participants (12 freerunning experts, 12 freerunning novices, and 12 laypeople) were asked to indicate their perception of motion aesthetics when watching video sequences of different freerunning performances. The results indicate that kinematic flight ratios and the observer’s sensory-motor experience are related to the aesthetic perception of the freerunning skill. As hypothesized, kinematic ratios of Webster performances perceived as more aesthetic are closer to the golden ratio, and Webster performances perceived as less aesthetic are farther away from the golden ratio; this is significant for expert and novice freerunners, but not for laypeople. Thus, we conclude that the aesthetic perception of complex motor skills is related to kinematic flight ratios and the observer’s sensory-motor expertise. Future work should incorporate such knowledge about kinematic ratios and how to address them during motor skill performances to create and perform aesthetically pleasing complex motor skills.

Nonalcoholic fatty liver disease (NAFLD) encompasses nonalcoholic steatohepatitis (NASH) and affects 25% of the global population. Although a plethora of experimental models for studying NASH have been proposed, still scarce findings regarding the hepatic metabolomic/molecular profile. In the present study, we sought to unravel the hepatic metabolomic profile of mice subjected to a hybrid model of NASH, by combining a Western diet and carbon tetrachloride administration, for 8 weeks, in male C57BL/6J and BALB/c mice. In both mouse strains, the main traits of NASH—metabolic (glucose intolerance profile), morphologic (extensive microvesicular steatosis and fibrosis, lobular inflammation, and adipose tissue-related inflammation/hypertrophy), and molecular (impaired Nrf2/NF-κB pathway dynamics and altered metabolomic profile)—were observed. The hepatic metabolomic profile revealed that the hybrid protocol impaired, in both strains, the abundance of branched chain-aromatic amino acids, carboxylic acids, and glycosyl compounds, that might be linked to the Nrf2 pathway activation. Moreover, we observed a strain-dependent hepatic metabolomic signature, in which the tricarboxylic acid metabolites and pyruvate metabolism were dissimilarly modulated in C57BL/6J and BALB/c mice. Thus, we provide evidence that the strain-dependent hepatic metabolomic profile might be linked to the distinct underlying mechanisms of NASH, also prospecting potential mechanistic insights into the corresponding disease.

The provided dataset describes the differential gene expression profile of human hepatoma HepaRG cells cultured in monolayer configuration upon treatment with chemical compounds with cholestatic potential, including food additives sunset yellow and tartrazine and cosmetic ingredient triclosan, while being exposed to a highly concentrated bile acid mixture. Whole genome microarray Affymetrix Human U133 plus 2.0 was used to obtain the raw data followed by normalization, summarization and background adjustments by means of Robust Multichip Average Express software. Raw data of the different conditions were included as .CEL files in the Gene Expression Omnibus with accession number GSE169072. These data may serve as the basis for further refinement studies to establish an adequate transcriptomic signature of chemical-induced cholestasis fit-for-purpose in screening the cholestatic liability of different types of chemical compounds.

Colorectal cancer (CRC), associated with an increased intake of processed red meats, saturated fats, and simple carbohydrates accompanied by low dietary fiber, fruits, and vegetables consumption, presents a high epidemiological burden. Connexin43 (Cx43) protein, which forms gap junctions or hemichannels, has tumor suppressor or oncogenic activities in a cancer type- and stage-dependent manner. Cx43 expression varies during colon carcinogenesis, and its functional role is not fully understood. Thus, we evaluated the implications of Cx43 heterologous deletion (Cx43+/−) during the early stages of a chemically induced model of colon carcinogenesis. Female C57BL/6J mice (wild-type or Cx43+/−) were submitted to a colon carcinogenesis model induced by 1,2 dimethylhydrazine (DMH). Mice were euthanized eight hours (week 7) or 30 weeks (week 37) after the last DMH administration to evaluate subacute colon toxicity outcomes or the burden of (pre)neoplastic lesions, respectively. At week 7, Cx43 deficiency inferred no alterations in the DMH-induced increase in systemic (peripheral blood), in situ (colonocytes) DNA damage, and apoptosis in the colonocytes. At week 30, Cx43+/− mice presented an increase in preneoplastic aberrant crypt foci (ACF) multiplicity, while no alterations were observed in colorectal adenoma (CRA) occurrence, multiplicity, volume, proliferation, growth, and β-catenin immunoexpression. Similarly, an in silico analysis of human CRA showed decreased mRNA expression of Cx43 with no correlation with proliferation, apoptosis, and β-catenin markers. These findings indicate the discrete role of Cx43 in the early stages of chemically induced mouse colon carcinogenesis.

Nitrogen oxide (NOx) emissions from maritime shipping produce ozone (O3) and hydroxyl radicals (OH), which in turn destroy methane (CH 4). The balance between this warming (due to O3) and cooling (due to CH4) determines the net effect of ship NOx on climate. Previous estimates of the chemical impact and radiative forcing (RF) of ship NOx have generally assumed that plumes of ship exhaust are instantly diluted into model grid cells spanning hundreds of kilometers, even though this is known to produce biased results. Here we improve the parametric representation of exhaust-gas chemistry developed in the GEOS-Chem chemical transport model (CTM) to provide the first estimate of RF from shipping that accounts for sub-grid-scale ship plume chemistry. The CTM now calculates O3 production and CH4 loss both within and outside the exhaust plumes and also accounts for the effect of wind speed.With the improved modeling of plumes, ship NOx perturbations are smaller than suggested by the ensemble of past global modeling studies, but if we assume instant dilution of ship NOx on the grid scale, the CTM reproduces previous model results. Our best estimates of the RF components from increasing ship NOx emissions by 1 Tg(N) yr-1 are smaller than that given in the past literature: +3.4±0.85mWm-2 (1σ confidence interval) from the short-lived ozone increase, -5.7±1.3mWm-2 from the CH4 decrease, and -1.7±0.7mWm-2 from the long-lived O 3 decrease that accompanies the CH4 change. The resulting net RF is -4.0±2.0mWm-2 for emissions of 1 Tg(N) yr-1. Due to non-linearity in O3 production as a function of background NO x, RF from large changes in ship NOx emissions, such as the increase since preindustrial times, is about 20% larger than this RF value for small marginal emission changes. Using sensitivity tests in one CTM, we quantify sources of uncertainty in the RF components and causes of the ±30% spread in past model results; the main source of uncertainty is the composition of the background atmosphere in the CTM, which is driven by model formulation (±10 to 20 %) and the plausible range of anthropogenic emissions (±10 %). © 2014 Author(s).

In the last two decades rodents have been on the rise as a dominant model for visual neuroscience. This is particularly true for earlier levels of information processing, but a number of studies have suggested that also higher levels of processing such as invariant object recognition occur in rodents. Here we provide a quantitative and comprehensive assessment of this claim by comparing a wide range of rodent behavioral and neural data with convolutional deep neural networks. These networks have been shown to capture hallmark properties of information processing in primates through a succession of convolutional and fully connected layers. We find that performance on rodent object vision tasks can be captured using low to mid-level convolutional layers only, without any convincing evidence for the need of higher layers known to simulate complex object recognition in primates. Our approach also reveals surprising insights on assumptions made before, for example, that the best performing animals would be the ones using the most abstract representations-which we show to likely be incorrect. Our findings suggest a road ahead for further studies aiming at quantifying and establishing the richness of representations underlying information processing in animal models at large.