bluuebunny/crossref_metadata_2025 huggingface dataset:
The prospects of emotional dogmatism
Authors: Harrison Eilidh
Published: October 2020

The idea that emotional experience is capable of lending immediate and defeasible justification to evaluative belief has been amassing significant support in recent years. The proposal that it is myanger, say, that justifies my belief that I’ve been wronged putatively provides us with an intuitive and naturalised explanation as to how we receive epistemic justification for a rich catalogue of our evaluative beliefs. However, despite the fact that this justificatory thesis of emotion is fundamentally an epistemological proposal, comparatively little has been done to explicitly isolatewhat it isabout emotions that bestows them with justificatory ability. The purpose of this paper is to provide a novel and thorough analysis into the prospects of phenomenology-based—ordogmatist—views of emotional justification. By surveying and rejecting various instantiations of the emotional dogmatist view, I endeavour to provide an inductive case for the conclusion that emotional phenomenology cannot be the seat of the emotions’ power to immediately justify evaluative belief.
AIP variant causing familial prolactinoma
Authors: Carty David M. , Harte Rachael , Drummond Russell S. , Ward Rebecca , Magid Kesson , Collier David , Owens Martina , Korbonits Márta
Published: October 2020

Pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene are increasingly recognised as a cause of familial isolated pituitary adenoma. AIP-associated tumours are most commonly growth hormone (GH) producing. In our cohort of 175 AIP mutation positive patients representing 93 kindreds, 139 (79%) have GH excess, 19 have prolactinoma (17 familial and 2 sporadic cases) and out of the 17 clinically non-functioning tumours 4 were subsequently operated and found to be GH or GH & prolactin immunopositive adenoma. Here we report a family with an AIP variant, in which multiple family members are affected by prolactinoma, but none with GH excess. To our knowledge this is the first reported family with an AIP pathogenic variant to be affected solely by prolactinoma. These data suggest that prolactinoma families represent a small subset of AIP mutation positive kindreds, and similar to young-onset sporadic prolactinomas, AIP screening would be indicated.
Writing Philosophy from the Periphery: Lixing as Foundational Empty Signifier in Tang Junyi’s Cultural Consciousness and Moral Reason
Authors: Major Philippe
Published: October 2020

This article adopts Ernesto Laclau’s notion of empty signifier to discuss Tang Junyi’s uses of the concept oflixing(‘reason’ or ‘rationality’) in his seminal workCultural Consciousness and Moral Reason(文化意識與道德理性; 1958). My dual goal, in doing so, is to bring to light the relations of power constitutive of the text’s discourse onlixingand relate them to the problematic of writing philosophy from the periphery. I argue that in this work,lixing’s dual referents—as a translation of ‘reason’ and as denoting a Neo-Confucian faculty to intuit moral truths—allow Tang to inscribe himself in a philosophical field designed to exclude non-Western philosophies, while at the same time enabling him to symbolically relegate Euro-American philosophy to a peripheral position by filling in the notion oflixingwith a content that legitimizes his own agenda. Tang could thus authorize his Confucian metaphysics by presenting it as the true content oflixing, understood not only as a universal faculty enabling humanity’s access to all that is universal, but also as a condition sine qua non of for one’s inclusion in the philosophical game. By attempting to co-opt the empty signifier (lixing/reason) for his own purposes, I argue Tang employs one of two possible strategies that can be adopted by those situated at the periphery in order to oppose the hegemon; one that leaves the structure of power relations intact but working in favor of the periphery.
Graphene quantum dots: From efficient preparation to safe renal excretion
Authors: Hadad Caroline , González-Domínguez José Miguel , Armelloni Silvia , Mattinzoli Deborah , Ikehata Masami , Istif Akcan , Ostric Adrian , Cellesi Francesco , Alfieri Carlo Maria , Messa Piergiorgio , Ballesteros Belén , Da Ros Tatiana
Published: October 2020

Carbon nanomaterials offer excellent prospects as therapeutic agents, and among them, graphene quantum dots (GQDs) have gained considerable interest thanks to their aqueous solubility and intrinsic fluorescence, which enable their possible use in theranostic approaches, if their biocompatibility and favorable pharmacokinetic are confirmed. We prepared ultra-small GQDs using an alternative, reproducible, top-down synthesis starting from graphene oxide with a nearly 100% conversion. The materials were tested to assess their safety, demonstrating good biocompatibility and ability in passing the ultrafiltration barrier using an in vitro model. This leads to renal excretion without affecting the kidneys. Moreover, we studied the GQDs in vivo biodistribution confirming their efficient renal clearance, and we demonstrated that the internalization mechanism into podocytes is caveolae-mediated. Therefore, considering the reported characteristics, it appears possible to vehiculate compounds to kidneys by means of GQDs, overcoming problems related to lysosomal degradation.
“Don’t Get Distracted!”: The Role of Social Robots’ Interaction Style on Users’ Cognitive Performance, Acceptance, and Non-Compliant Behavior
Authors: Maggi Gianpaolo , Dell’Aquila Elena , Cucciniello Ilenia , Rossi Silvia
Published: October 2020

Social robots are developed to provide companionship and assistance in the daily life of the children, older, and disable people but also have great potential as educational technology by facilitating learning. In these application areas, a social robot can take the role of a coach by training and assisting individuals also in cognitive tasks. Since a robot’s interaction style affects users’ trust and acceptance, customizing its behavior to the proposed tasks could, potentially, have an impact on the users’ performance. To investigate these phenomena, we enrolled sixty volunteers and endowed a social robot with a friendly and an authoritarian interaction style. The aim was to explore whether and how the robot’s interaction style could enhance users’ cognitive performance during a psychometric evaluation. The results showed that the authoritarian interaction style seems to be more appropriate to improve the performance when the tasks require high cognitive demands. These differences in cognitive performance between the groups did not depend on users’ intrinsic characteristics, such as gender and personality traits. Nevertheless, in the authoritarian condition, participants’ cognitive performance was related to their trust and the acceptance of the technology. Finally, we found that users’ non-compliant behavior was not related to their personality traits. This finding indirectly supports the role of the robot’s interaction style in influencing the compliance behavior of the users.
Unusual Presentations of Trisomy 21
Authors: Desai Purvi , Desai Kairavi , Kathrotiya Kalpana , Chauhan Keshvi , Chauhan Binodini
Published: October 2020

Trisomy 21 is the most common aneuploidy in liveborn infants. Most of the soft markers for trisomy 21 are non-specific and transient. We present 2 cases which had abnormalities which are very rarely associated with Down’s syndrome. In the first case, the patient had bilateral congenital cataract along with an absent nasal bone. In the second case, the patient had severe asymmetric fetal growth restriction at 20 weeks with other multi-system abnormalities. With detailed ultrasound scanning and thorough investigation, we could diagnose trisomy 21 even with such unusual presentations.
Principles of Tort Law
Authors: Mulheron Rachael
Published: October 2020

Presenting the law of tort as a body of principles, this authoritative textbook gives an incisive understanding of the subject. Each tort is carefully structured and examined within a consistent analytical framework that guides students through its preconditions, elements, defences and remedies. Clear summaries and comparisons accompany the detailed exposition, and further support is provided by diagrams and tables which clarify complex aspects of the law. Critical discussion of legal judgments encourages students to develop strong analytical and case-reading skills, whilst key reform proposals and leading cases from other jurisdictions illustrate different potential solutions to conundrums in tort law. A rich companion website, featuring semesterly updates alongside ten additional chapters on more advanced topics, completes the learning package. This new edition has been updated to take account of important cases, legislative developments and law reform studies since July 2015.
Making Sense of “Good” and “Bad”: A Deonance and Fairness Approach to Abusive Supervision and Prosocial Impact
Authors: Johnson Michael A. , Priesemuth Manuela , Bigelow Bailey
Published: October 2020

This article challenges the unidimensional view of abusive supervisors and examines how employees respond to abuse when the transgressing boss also has a positive impact on others. Drawing on deonance and fairness theory, we propose competing hypotheses about the influence of prosocial impact. Specifically, we use deonance theory to suggest that prosocial impact might buffer the effects of abusive supervision. Alternatively, we incorporate fairness theory to predict that prosocial impact strengthens injustice perceptions and thereby worsens consequences of abuse. Two field studies show support for fairness theory, demonstrating that employees perceive greater injustice, and show stronger retaliatory behaviors, when the abusive supervisor makes a positive difference in the workplace. A final field study replicates these results, while also testing the underlying cognitive process employees use to assess the interplay between “good” and “bad” supervisory characteristics. This article contributes insights to abusive supervision, prosocial impact, organizational justice, and behavioral ethics literatures.
Activity patterns in a feline assemblage in south-west Mexico, and their relationship with prey species
Authors: Hernández-Sánchez Alejandro , Santos-Moreno Antonio
Published: October 2020

Several species of neotropical felines are morphologically and ecologically similar, and are sympatric along large areas of their distribution. This requires mechanisms to allow their coexistence, such as temporal segregation of their activities. The aim of this study was to evaluate the relation between activity patterns of felines and their prey using camera trapping data and their seasonal variation in two tropical environments in south-western Mexico. ExceptingPuma concolor, activity patterns for each feline species did not differ significantly between seasons nor between vegetation types. Activity patterns did not differ significantly between species of similar size: mid-sized species had high activity pattern overlaps in the medium forest while large-sized species overlapped to a lesser extent in the cloud forest.Leopardus wiediidiffered from large-sized predators in its activity patterns. We recorded a relatively high temporal overlap between felines and their main prey species, particularly in the periods of maximum activity. We found no evidence of temporal segregation between the felines of the Sierra Norte region of Oaxaca and we suggest their coexistence is mediated by the selection of prey with different activity patterns.
Information brokerage in Caribbean coral reef governance networks
Authors: Turner Rachel A , Forster Johanna , Peterson Angelie M , Mahon Robin , Fitzsimmons Clare
Published: October 2020

Poor connectivity between diverse resource users and complex wider governance networks is a challenge in environmental governance. Organizations that ‘broker’ interactions among these relationships are expected to improve governance outcomes. Here, we used semi-structured interviews and social network analysis to identify actors in positions to broker coral reef-related information to and from resource users and to assess the performance of these brokers. Representatives (n = 262) of actor groups were interviewed, including local and national government, non-governmental organizations (NGOs), community organizations and resource user groups from 12 communities across four Caribbean countries, to map information-sharing networks and to identify brokers. Broker performance was assessed through separate interviews with coral reef resource users (n = 545). The findings show that marine NGOs were the highest-functioning brokers. Where such local-level organizations were absent, government agencies in reef management roles acted as brokers, but their performance was lower. Actors in brokerage positions did not always effectively share information, with broker performance being positively correlated with network brokerage scores. The results further our understanding of the roles of brokers in different governance contexts. Identifying those in brokerage positions and supporting their roles in connecting local resource users to wider governance networks could encourage functional brokerage and enhance reef management outcomes.
The efficacy of ‘high in’ warning labels, health star and traffic light front-of-package labelling: an online randomised control trial
Authors: Vanderlee Lana , Franco-Arellano Beatriz , Ahmed Mavra , Oh Angela , Lou Wendy , L’Abbé Mary R
Published: October 2020

Objective:

To examine the impact of front-of-package (FOP) labels on perceived healthfulness, purchasing intentions and understanding of common FOP systems.

Design

A parallel, open-label design randomised participants to different FOP labelling conditions: ‘high in’ warning labels (WL), multiple traffic light labelling (TLL), health star ratings (HSR) (all displayed per serving) or control with no interpretive FOP labelling. Participants completed a brief educational session via a smartphone application and two experimental tasks. In Task 1, participants viewed healthy or unhealthy versions of four products and rated healthiness and purchasing intention on a seven-point Likert-type scale. In Task 2, participants ranked three sets of five products from healthiest to least healthy.

Setting

Online commercial panel.

Participants

Canadian residents ≥ 18 years who were involved in household grocery shopping, owned a smartphone and met minimum screen requirements.

Results

Data from 1997 participants (n 500/condition) were analysed. Task 1: across most product categories, the TLL and HSR increased perceived healthiness of healthier products. All FOP systems decreased perceived healthiness of less healthy products. Similar, albeit dampened, effects were seen regarding purchasing intentions. Task 2: participants performed best in the HSR, followed by the TLL, WL and control conditions. Lower health literacy was associated with higher perceived healthiness and purchasing intentions and poorer ranking task performance across all conditions.

Conclusions

All FOP labelling systems, after a brief educational session, improved task performance across a wide spectrum of foods. This effect differed depending on the nutritional quality of the products and the information communicated on labels.

Trial Registration: NCT03290118.
NATURALISM
Authors: Oppy Graham
Published: October 2020

I offer a minimal characterization of naturalism, with ontological, epistemological, psychological and evaluative dimensions. I explain why naturalism is attractive. I note that naturalists disagree among themselves about, among other things, the nature of values, beliefs, and abstractions. I close by responding to some standard objections to naturalism.
THEISM, NATURALISM, AND INVISIBLE GARDENERS
Authors: Rauser Randal D.
Published: October 2020

In this article, I consider the famous Invisible Gardener Parable which aims to show that theism is not a viable theory because it can be endlessly amended to accommodate for prima facie disconfirming data. I point out that the parable fails to consider how tolerance for theory adjustment is relative to the perceived explanatory power of the theory. I also point out that naturalism is no less subject to adaptation than is theism. Thus, if endless adaptability constitutes an objection for theism then it does so for naturalism as well.
SCIENTISM VERSUS THE THEORY OF MIND
Authors: Rosenberg Alex
Published: October 2020

Many philosophers call themselves ‘naturalists’ because they believe theism is incompatible with science. However, many also hold that science is compatible with many other theistic beliefs about morality, free will, the mind, and the meaning of life. Those naturalists who reject these other beliefs need a different label for their view. This article recommends the term ‘scientism’.
Pubertal timing and self-harm: a prospective cohort analysis of males and females
Authors: Roberts Elystan , Joinson Carol , Gunnell David , Fraser Abigail , Mars Becky
Published: October 2020

Aims

Early puberty is associated with an increased risk of self-harm in adolescent females but results for males are inconsistent. This may be due to the use of subjective measures of pubertal timing, which may be biased. There is also limited evidence for the persistence of pubertal timing effects beyond adolescence, particularly in males. The primary aim of the current study was therefore to examine the association between pubertal timing and self-harm in both sexes during adolescence and young adulthood, using an objective measure of pubertal timing (age at peak height velocity; aPHV). A secondary aim was to examine whether this association differs for self-harm with v. without suicidal intent.

Methods

The sample (n = 5369, 47% male) was drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort study. Mixed-effects growth curve models were used to calculate aPHV. Lifetime history of self-harm was self-reported at age 16 and 21 years, and associated suicidal intent was examined at age 16 years. Associations were estimated using multivariable logistic regression adjusted for a range of confounders. Missing data were imputed using Multiple Imputation by Chained Equations.

Results

Later aPHV was associated with a reduced risk of self-harm at 16 years in both sexes (females: adjusted per-year increase in aPHV OR 0.85; 95% CI 0.75–0.96; males: OR 0.72; 95% CI 0.59–0.88). Associations were similar for self-harm with and without suicidal intent. There was some evidence of an association by age 21 years in females (adjusted per-year increase in aPHV OR 0.91; 95% CI 0.80–1.04), although the findings did not reach conventional levels of significance. There was no evidence of an association by age 21 years in males (adjusted per-year increase in aPHV OR 0.99; 95% CI 0.74–1.31).

Conclusions

Earlier developing adolescents represent a group at increased risk of self-harm. This increased risk attenuates as adolescents transition into adulthood, particularly in males. Future research is needed to identify the modifiable mechanisms underlying the association between pubertal timing and self-harm risk in order to develop interventions to reduce self-harm in adolescence.
Faulting Processes Unveiled by Magnetic Properties of Fault Rocks
Authors: Yang Tao , Chou Yu‐Min , Ferré Eric C. , Dekkers Mark J. , Chen Jianye , Yeh En‐Chao , Tanikawa Wataru
Published: October 2020

As iron‐bearing minerals—ferrimagnetic minerals in particular—are sensitive to stress, temperature, and presence of fluids in fault zones, their magnetic properties provide valuable insights into physical and chemical processes affecting fault rocks. Here, we review the advances made in magnetic studies of fault rocks in the past three decades. We provide a synthesis of the mechanisms that account for the magnetic changes in fault rocks and insights gained from magnetic research. We also integrate nonmagnetic approaches in the evaluation of the magnetic properties of fault rocks. Magnetic analysis unveils microscopic processes operating in the fault zones such as frictional heating, energy dissipation, and fluid percolation that are otherwise difficult to constrain. This makes magnetic properties suited as a “strain indicator,” a “geothermometer,” and a “fluid tracer” in fault zones. However, a full understanding of faulting‐induced magnetic changes has not been accomplished yet. Future research should focus on detailed magnetic property analysis of fault zones including magnetic microscanning and magnetic fabric analysis. To calibrate the observations on natural fault zones, laboratory experiments should be carried out that enable to extract the exact physicochemical conditions that led to a certain magnetic signature. Potential avenues could include (1) magnetic investigations on natural and synthetic fault rocks after friction experiments, (2) laboratory simulation of fault fluid percolation, (3) paleomagnetic analysis of postkinematic remanence components associated with faulting processes, and (4) synergy of interdisciplinary approaches in mineral‐magnetic studies. This would help to place our understanding of the microphysics of faulting on a much stronger footing.
An Ephemeral Red Arc Appeared at 68° MLat at a Pseudo Breakup During Geomagnetically Quiet Conditions
Authors: Oyama S. , Shinbori A. , Ogawa Y. , Kellinsalmi M. , Raita T. , Aikio A. , Vanhamäki H. , Shiokawa K. , Virtanen I. , Cai L. , Workayehu A. B. , Pedersen M. , Kauristie K. , Tsuda T. T. , Kozelov B. , Demekhov A. , Yahnin A. , Tsuchiya F. , Kumamoto A. , Kasahara Y. , Matsuoka A. , Shoji M. , Teramoto M. , Lester M.
Published: October 2020

Various subauroral optical features have been studied by analyzing data collected during periods of geomagnetic disturbances. Most events have been typically found at geomagnetic latitudes of 45–60°. In this study, however, we present a red arc event found at geomagnetic 68° north (L ≈ 7.1) in the Scandinavian sector during a period of geomagnetically quiet conditions within a short intermission between two high‐speed solar wind events. The red arc appeared to coincide with a pseudo breakup at geomagnetic 71–72°N and a rapid equatorward expansion of the polar cap. However, the red arc disappeared in approximately 7 min. Simultaneous measurements with the Swarm A/C satellites indicated the appearance of the red arc at the ionospheric trough minimum and a conspicuous enhancement of the electron temperature, suggesting the generation of the arc by heat flux. Since there are meaningful differences in the red arc features from already‐known subauroral optical features such as the stable auroral red (SAR) arc, we considered that the red arc is a new phenomenon. We suggest that the ephemeral red arc may represent the moment of SAR arc birth associated with substorm particle injection, which is generally masked by bright dynamic aurorae.
On the Relationships Between Radar Reflectivity and Rainfall Rate and Kinetic Energy Resulting From a Weibull Drop Size Distribution
Authors: Assouline Shmuel
Published: October 2020

The rainfall rate is a crucial variable in modeling runoff and water erosion. Rainfall rates present a very large spatial and temporal variability. Radars are used to estimate the spatial and temporal changes in rainfall rates during storms. The radar reflectivity is strongly affected by the drop size distribution (DSD) that results from the relative intensity of the microphysical processes involved in rainfall formation. One of the mathematical models applied to quantify the DSD is the Weibull function. Rainfall rate and kinetic energy, and radar reflectivity, are all related to different moments of the DSD. An analytical expression for these moments is proposed in the case of the Weibull distribution. The resulting relationships between radar reflectivity, rainfall rate, and kinetic energy are presented. The use of a scaled DSD that is independent of rainfall rate and characterizes a specific location allows an a priori estimate of relationships between radar reflectivity, rainfall rate, and kinetic energy that will be also characteristics of that location. Radar reflectivity can be used to estimate the kinetic energy of rainfall events. This extends the application of radar to agriculture and environmental purposes such as potential rainfall damages estimates in terms of soil loss, erosion, and sediment transport.
Alteration of the steroidogenesis in boys with autism spectrum disorders
Authors: Janšáková Katarína , Hill Martin , Čelárová Diana , Celušáková Hana , Repiská Gabriela , Bičíková Marie , Máčová Ludmila , Ostatníková Daniela
Published: October 2020

The etiology of autism spectrum disorders (ASD) remains unknown, but associations between prenatal hormonal changes and ASD risk were found. The consequences of these changes on the steroidogenesis during a postnatal development are not yet well known. The aim of this study was to analyze the steroid metabolic pathway in prepubertal ASD and neurotypical boys. Plasma samples were collected from 62 prepubertal ASD boys and 24 age and sex-matched controls (CTRL). Eighty-two biomarkers of steroidogenesis were detected using gas-chromatography tandem-mass spectrometry. We observed changes across the whole alternative backdoor pathway of androgens synthesis toward lower level in ASD group. Our data indicate suppressed production of pregnenolone sulfate at augmented activities of CYP17A1 and SULT2A1 and reduced HSD3B2 activity in ASD group which is partly consistent with the results reported in older children, in whom the adrenal zona reticularis significantly influences the steroid levels. Furthermore, we detected the suppressed activity of CYP7B1 enzyme readily metabolizing the precursors of sex hormones on one hand but increased anti-glucocorticoid effect of 7α-hydroxy-DHEA via competition with cortisone for HSD11B1 on the other. The multivariate model found significant correlations between behavioral indices and circulating steroids. From dependent variables, the best correlation was found for the social interaction (28.5%). Observed changes give a space for their utilization as biomarkers while reveal the etiopathogenesis of ASD. The aforementioned data indicate a direction of the future research with a focus on the expression and functioning of genes associated with important steroidogenic enzymes in ASD patients from early childhood to adrenarche.
Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity
Authors: Viviani Roberto , Messina Irene , Bosch Julia E. , Dommes Lisa , Paul Anna , Schneider Katharina L. , Scholl Catharina , Stingl Julia C.
Published: October 2020

The polymorphic drug-metabolizing enzyme CYP2D6, which is responsible for the metabolism of most psychoactive compounds, is expressed not only in the liver, but also in the brain. The effects of its marked genetic polymorphism on the individual capacity to metabolize drugs are well known, but its role in metabolism of neural substrates affecting behavior personality or cognition, suggested by its CNS expression, is a long-standing unresolved issue. To verify earlier findings suggesting a potential effect on attentional processes, we collected functional imaging data, while N = 415 participants performed a simple task in which the reward for correct responses varied. CYP2D6 allelic variants predicting higher levels of enzymatic activity level were positively associated with cortical activity in occipito-parietal areas as well as in a right lateralized network known to be activated by spatial attentional tasks. Reward-related modulation of activity in cortical areas was more pronounced in poor metabolizers. In conjunction with effects on reaction times, our findings provide evidence for reduced cognitive efficiency in rapid metabolizers compared to poor metabolizers in on-task attentional processes manifested through differential recruitment of a specific neural substrate.
Requirement for Serine-384 in Caspase-2 processing and activity
Authors: Zamaraev Alexey V. , Volik Pavel I. , Nilov Dmitry K. , Turkina Maria V. , Egorshina Aleksandra Yu. , Gorbunova Anna S. , Iarovenko Svetlana Iu. , Zhivotovsky Boris , Kopeina Gelina S.
Published: October 2020

Caspase-2 is a unique and conservative cysteine protease which plays an important role in several cellular processes including apoptotic cell death. Although the molecular mechanisms of its activation remain largely unclear, a major role belongs to the architecture of the caspase-2 active center. We demonstrate that the substitution of the putative phosphorylation site of caspase-2, Serine-384 to Alanine, blocks caspase-2 processing and decreases its enzymatic activity. Strikingly, in silico analysis using molecular dynamics simulations has shown that Serine-384 is crucially involved in interactions within the caspase-2 active center. It stabilizes Arginine-378, which forms a crucial hydrogen bond with the aspartate residue of a substrate. Hence, Serine-384 is essential for supporting a proper architecture of the active center of caspase-2. Moreover, molecular modeling strongly proved steric inaccessibility of Ser-384 to be phosphorylated. Importantly, a multiple alignment has demonstrated that both Serine-384 and Arg-378 residues are highly conservative across all members of caspase family, which allows us to suggest that this diade is indispensable for caspase processing and activity. Spontaneous mutations in this diade might influence oncosuppressive function of caspases, in particular of caspase-2. Likewise, the mutation of Ser-384 is associated with the development of lung squamous cell carcinoma and adenocarcinoma. Taken together, we have uncovered a central feature of the caspase-2 activation mechanism which is crucial for the regulation of its signaling network.
Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C+ CD8+ T cells
Authors: Zhu Jiaqi , Feng Bing , Xu Yanping , Chen Wenyi , Sheng Xinyu , Feng Xudong , Shi Xiaowei , Liu Jingqi , Pan Qiaoling , Yu Jiong , Li Lanjuan , Cao Hongcui
Published: October 2020

Systemic inflammatory processes, including alveolar injury, cytokine induction, and neutrophil accumulation, play key roles in the pathophysiology of acute lung injury (ALI). The immunomodulatory effects of mesenchymal stem cells (MSCs) can contribute to the treatment of inflammatory disorders. In previous studies, the focus was on innate immune cells and the effects of MSCs on ALI through CD8+T cells remain unclear. In the present study, lipopolysaccharide (LPS) was used to induce ALI in mice. ALI mice were treated with MSCs via intratracheal instillation. Survival rate, histopathological changes, protein levels, total cell count, cytokine levels, and chemokine levels in alveolar lavage fluid were used to determine the efficacy of MSCs. Mass cytometry and single-cell RNA sequencing (scRNA-seq) were used to characterize the CD8+T cells in the lungs. Ly6C−CD8+T cells are prevalent in normal mice, whereas a specialized effector phenotype expressing a high level of Ly6C is predominant in advanced disease. MSCs significantly mitigated ALI and improved survival. MSCs decreased the infiltration of CD8+T cells, especially Ly6C+CD8+T cells into the lungs. Mass cytometry revealed that CD8+T cells expressing high Ly6C and CXCR3 levels caused tissue damage in the lungs of ALI mice, which was alleviated by MSCs. The scRNA-seq showed that Ly6C+CD8+T cells exhibited a more activated phenotype and decreased expression of proinflammatory factors that were enriched the most in immune chemotaxis after treatment with MSCs. We showed that CD8+T cells play an important role in MSC-mediated ALI remission, and both infiltration quantity and proinflammatory function were inhibited by MSCs, indicating a potential mechanism for therapeutic intervention.
Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence
Authors: Walens Andrea , Lin Jiaxing , Damrauer Jeffrey S. , McKinney Brock , Lupo Ryan , Newcomb Rachel , Fox Douglas B. , Mabe Nathaniel W. , Gresham Jeremy , Sheng Zhecheng , Sibley Alexander B. , De Buysscher Tristan , Kelkar Hemant , Mieczkowski Piotr A. , Owzar Kouros , Alvarez James V.
Published: October 2020

The survival and recurrence of residual tumor cells following therapy constitutes one of the biggest obstacles to obtaining cures in breast cancer, but it remains unclear how the clonal composition of tumors changes during relapse. We use cellular barcoding to monitor clonal dynamics during tumor recurrence in vivo. We find that clonal diversity decreases during tumor regression, residual disease, and recurrence. The recurrence of dormant residual cells follows several distinct routes. Approximately half of the recurrent tumors exhibit clonal dominance with a small number of subclones comprising the vast majority of the tumor; these clonal recurrences are frequently dependent upon Met gene amplification. A second group of recurrent tumors comprises thousands of subclones, has a clonal architecture similar to primary tumors, and is dependent upon the Jak/Stat pathway. Thus the regrowth of dormant tumors proceeds via multiple routes, producing recurrent tumors with distinct clonal composition, genetic alterations, and drug sensitivities.
Human running performance from real-world big data
Authors: Emig Thorsten , Peltonen Jussi
Published: October 2020

Wearable exercise trackers provide data that encode information on individual running performance. These data hold great potential for enhancing our understanding of the complex interplay between training and performance. Here we demonstrate feasibility of this idea by applying a previously validated mathematical model to real-world running activities of  ≈ 14,000 individuals with ≈ 1.6 million exercise sessions containing duration and distance, with a total distance of ≈ 20 million km. Our model depends on two performance parameters: an aerobic power index and an endurance index. Inclusion of endurance, which describes the decline in sustainable power over duration, offers novel insights into performance: a highly accurate race time prediction and the identification of key parameters such as the lactate threshold, commonly used in exercise physiology. Correlations between performance indices and training volume and intensity are quantified, pointing to an optimal training. Our findings hint at new ways to quantify and predict athletic performance under real-world conditions.
Tailoring poplar lignin without yield penalty by combining a null and haploinsufficient CINNAMOYL-CoA REDUCTASE2 allele
Authors: De Meester Barbara , Madariaga Calderón Barbara , de Vries Lisanne , Pollier Jacob , Goeminne Geert , Van Doorsselaere Jan , Chen Mingjie , Ralph John , Vanholme Ruben , Boerjan Wout
Published: October 2020

Lignin causes lignocellulosic biomass recalcitrance to enzymatic hydrolysis. Engineered low-lignin plants have reduced recalcitrance but often exhibit yield penalties, offsetting their gains in fermentable sugar yield. Here, CRISPR/Cas9-generated CCR2(−/*) line 12 poplars have one knockout CCR2 allele while the other contains a 3-bp deletion, resulting in a 114I115A-to-114T conversion in the corresponding protein. Despite having 10% less lignin, CCR2(−/*) line 12 grows normally. On a plant basis, the saccharification efficiency of CCR2(−/*) line 12 is increased by 25–41%, depending on the pretreatment. Analysis of monoallelic CCR2 knockout lines shows that the reduced lignin amount in CCR2(−/*) line 12 is due to the combination of a null and the specific haploinsufficient CCR2 allele. Analysis of another CCR2(−/*) line shows that depending on the specific CCR2 amino-acid change, lignin amount and growth can be affected to different extents. Our findings open up new possibilities for stably fine-tuning residual gene function in planta.
Structural basis for the transition from translation initiation to elongation by an 80S-eIF5B complex
Authors: Wang Jinfan , Wang Jing , Shin Byung-Sik , Kim Joo-Ran , Dever Thomas E. , Puglisi Joseph D. , Fernández Israel S.
Published: October 2020

Recognition of a start codon by the initiator aminoacyl-tRNA determines the reading frame of messenger RNA (mRNA) translation by the ribosome. In eukaryotes, the GTPase eIF5B collaborates in the correct positioning of the initiator Met-tRNAiMet on the ribosome in the later stages of translation initiation, gating entrance into elongation. Leveraging the long residence time of eIF5B on the ribosome recently identified by single-molecule fluorescence measurements, we determine the cryoEM structure of the naturally long-lived ribosome complex with eIF5B and Met-tRNAiMet immediately before transition into elongation. The structure uncovers an unexpected, eukaryotic specific and dynamic fidelity checkpoint implemented by eIF5B in concert with components of the large ribosomal subunit.
Characterization of two types of intranuclear hepatocellular inclusions in NAFLD
Authors: Schwertheim Suzan , Kälsch Julia , Jastrow Holger , Schaefer Christoph Matthias , Theurer Sarah , Ting Saskia , Canbay Ali , Wedemeyer Heiner , Schmid Kurt Werner , Baba Hideo Andreas
Published: October 2020

Nuclear inclusions (NI) are a common finding in hepatocytes from patients with liver disease especially in diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) but studies examining the shape and content of these inclusions in detail are lacking. In this study we define two distinct types of NI in NAFLD: inclusions bounded by the nuclear membrane, containing degenerative cell organelles and heterolysosomes (type1) and inclusions with deposits of glycogen but without any kind of organelles and delimiting membrane (type2). NI in 77 paraffin-embedded patients of NAFLD including NAFL and non-alcoholic steatohepatitis (NASH) were analyzed. In 4–12% of type1 NI immunopositivity for the autophagy-associated proteins LC3B, ubiquitin, p62/sequestosome1, cathepsin D and cathepsin B were detected with co-localizations of ubiquitin and p62; type2 NI showed no immunoreactivity. Three-dimensional reconstructions of isolated nuclei revealed that NI type1 are completely enclosed within the nucleus, suggesting that NI, although probably derived from cytoplasmic invaginations, are not just simple invaginations. Our study demonstrates two morphologically different types of inclusions in NAFLD, whereby both gained significantly in number in advanced stages. We suggest that the presence of autophagy-associated proteins and degenerated organelles within type1 NI plays a role in disease progression.
A periodic pumping technique of soil gas for 222Rn stabilization in large calibration chambers: part 2—theoretical formulation and experimental validation
Authors: Shetty Trilochana , Mayya Y. S. , Kumara K. Sudeep , Sahoo B. K. , Sapra B. K. , Karunakara N.
Published: October 2020

In an adjoining publication, we demonstrated the novel technique to harvest soil gas of natural origin as a highly efficient source of 222Rn for calibration applications in a large volume 222Rn calibration chamber. Its advantages over the use of conventional high strength 226Ra sources, such as the capability to serve as a non-depleting reservoir of 222Rn and achieve the desired concentration inside the calibration chamber within a very short time, devoid of radiation safety issues in source handling and licensing requirements from the regulatory authority, were discussed in detail. It was also demonstrated that stability in the 222Rn concentration in large calibration chambers could be achieved within ± 20% deviation from the desired value through a semi-dynamic mode of injection in which 222Rn laden air was periodically pumped to compensate for its loss due to leak and decay. The necessity of developing a theory for determining the appropriate periodicity of pumping was realized to get good temporal stability with a universally acceptable deviation of ≤ ± 10% in the 222Rn concentration. In this paper, we present a mathematical formulation to determine the injection periods (injection pump ON and OFF durations) for the semi-dynamic operation to achieve long term temporal stability in the 222Rn concentration in the chamber. These computed pumping parameters were then used to efficiently direct the injection of soil gas into the chamber. We present the mathematical formulation, and its experimental validations in a large volume calibration chamber (22 m3). With this, the temporal stability of 222Rn concentration in the chamber was achieved with a deviation of ~ 3% from the desired value.
Molecular phylogenetic, population genetic and demographic studies of Nodularia douglasiae and Nodularia breviconcha based on CO1 and 16S rRNA
Authors: Choi Eun Hwa , Kim Gyeongmin , Cha Seung Hyun , Lee Jun-Sang , Ryu Shi Hyun , Suk Ho Young , Lee Young Sup , Baek Su Youn , Hwang Ui Wook
Published: October 2020

Freshwater mussels belonging to the genus Nodularia (Family Unionidae) are known to be widely distributed in East Asia. Although phylogenetic and population genetic studies have been performed for these species, there still remain unresolved questions in their taxonomic status and biogeographic distribution pathways. Here, the nucleotide sequences of CO1 and 16S rRNA were newly determined from 86 N. douglasiae and 83 N. breviconcha individuals collected on the Korean Peninsula. Based on these data, we revealed the following results: (1) N. douglasiae can be divided into the three genetic clades of A (only found in Korean Peninsula), B (widely distributed in East Asia), and C (only found in the west of China and Russia), (2) the clade A is not an independent species but a concrete member of N. douglasiae given the lack of genetic differences between the clades A and B, and (3) N. breviconcha is not a subspecies of N. douglasiae but an independent species apart from N. douglasiae. In addition, we suggested the plausible scenarios of biogeographic distribution events and demographic history of Nodularia species.
New clues on the Atlantic eels spawning behavior and area: the Mid-Atlantic Ridge hypothesis
Authors: Chang Yu-Lin K. , Feunteun Eric , Miyazawa Yasumasa , Tsukamoto Katsumi
Published: October 2020

The Sargasso Sea has long been considered as the only spawning area for Atlantic eels, despite the absence of direct observations. The present study raises a novel scenario, deviating from Schmidt’s dogma, begins with a review of historical and recent observations that were combined to build up a global theory on spawning ecology and migration behavior of Atlantic eels. From this, it is argued that a favorable spawning area could be located eastward of Sargasso Sea at the intersection between the Mid-Atlantic Ridge and the oceanic fronts. Ocean circulation models combined with 3D particle-tracking method confirmed that spawning at this specific area would result in larval distribution fitting the field observation. This study explores the hypothesis that leptocephali are able to swim and orientate to reach their specific growth areas. It proposes a novel framework about spawning ecology, based on orientation, navigation and meeting cues of silver eels to the spawning area. Together this framework may serve as a stepping-stone for solving the long-lasting mystery of eel reproduction which first came out 2,400 years ago and promotes the understanding of oceanic migration and reproduction of marine organisms.
Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting
Authors: Bauza Guillermo , Pasto Anna , Mcculloch Patrick , Lintner David , Brozovich Ava , Niclot Federica Banche , Khan Ilyas , Francis Lewis W. , Tasciotti Ennio , Taraballi Francesca
Published: October 2020

Cartilage repair in osteoarthritic patients remains a challenge. Identifying resident or donor stem/progenitor cell populations is crucial for augmenting the low intrinsic repair potential of hyaline cartilage. Furthermore, mediating the interaction between these cells and the local immunogenic environment is thought to be critical for long term repair and regeneration. In this study we propose articular cartilage progenitor/stem cells (CPSC) as a valid alternative to bone marrow-derived mesenchymal stem cells (BMMSC) for cartilage repair strategies after trauma. Similar to BMMSC, CPSC isolated from osteoarthritic patients express stem cell markers and have chondrogenic, osteogenic, and adipogenic differentiation ability. In an in vitro 2D setting, CPSC show higher expression of SPP1 and LEP, markers of osteogenic and adipogenic differentiation, respectively. CPSC also display a higher commitment toward chondrogenesis as demonstrated by a higher expression of ACAN. BMMSC and CPSC were cultured in vitro using a previously established collagen-chondroitin sulfate 3D scaffold. The scaffold mimics the cartilage niche, allowing both cell populations to maintain their stem cell features and improve their immunosuppressive potential, demonstrated by the inhibition of activated PBMC proliferation in a co-culture setting. As a result, this study suggests articular cartilage derived-CPSC can be used as a novel tool for cellular and acellular regenerative medicine approaches for osteoarthritis (OA). In addition, the benefit of utilizing a biomimetic acellular scaffold as an advanced 3D culture system to more accurately mimic the physiological environment is demonstrated.
Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia
Authors: Wu Zheng , Sun Fangling , Li Zijie , Liu Min , Tian Xin , Guo Deyu , Wei Penghu , Shan Yongzhi , Liu Tingting , Guo Min , Zhu Zixin , Zheng Wenrong , Wang Yufeng , Zhao Guoguang , Wang Wen
Published: October 2020

Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.