Miracle-dz/UniFAR-FTUs huggingface dataset:
Toward a neuropsychology of political orientation: exploring ideology in patients with frontal and midbrain lesions

How do people form their political beliefs? In an effort to address this question, we adopt a neuropsychological approach. In a natural experiment, we explored links between neuroanatomy and ideological preferences in two samples of brain lesion patients in New York City. Specifically, we compared the political orientations of patients with frontal lobe lesions, patients with amygdala lesions and healthy control subjects. Lesion type classification analyses revealed that people with frontal lesions held more conservative (or less liberal) beliefs than those with anterior temporal lobe lesions or no lesions. Additional analyses predicting ideology by extent of damage provided convergent evidence that greater damage in the dorsolateral prefrontal cortex—but not the amygdala—was associated with greater conservatism. These findings were robust to model specifications that adjusted for demographic, mood, and affect-related variables. Although measures of executive function failed to mediate the relationship between frontal lesions and ideology, our findings suggest that the prefrontal cortex may play a role in promoting the development of liberal ideology. Our approach suggests useful directions for future work to address the issue of whether biological developments precede political attitudes or vice versa—or both. This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms’.
Combining and managing work-family-study roles and perceptions of institutional support

ABSTRACT Students registering for distance education degree-level study frequently cite flexibility as a factor influencing their choice for this mode of study, but little is known about how students manage simultaneous and/or potentially conflicting roles. This study used a self-report open-ended online survey, completed by 348 tertiary-level final-year undergraduate distance students in the United Kingdom. Respondents were asked how they managed to combine roles and their perceptions of university support. After a thematic analysis, three main themes were identified: building rituals and habits for learning, navigating online environments and contexts for learning, and responding to the pressures and problems that hindered their learning. Students expressed a desire for more proactive support from tutors. From the university, students wanted realistic and practical guidance and planning tools to prepare themselves and others (such as their employers and family) for the likely practical requirements of distance study when combining multiple roles.
Characterization of Carbon Based Nanoparticles Dispersion in Aqueous Solution Using Dynamic Light Scattering Technique

Characterization of physicochemical properties of nanoparticles in aqueous environment prior to conducting hazard studies is strongly recommended by many scientific organizations. In this work we studied the dissolution behaviour and physicochemical properties of carbon based nanoparticles in aqueous solution. The time evolution of the size distribution and the state of dispersion of carbon black and carbon nanotubes in physiological solution have been investigated by means of Dynamic Light Scattering technique. The influence of mechanical agitation such as sonication and stirring on the agglomeration state and particle size distribution has been investigated. However, such processes seem to have little or no effect as far as agglomeration is concerned.
Integrating region memory management and tag-free generational garbage collection

Abstract We present a region-based memory management scheme with support for generational garbage collection. The scheme features a compile-time region inference algorithm, which associates values with logical regions, and builds on a region type system that deploys region types at runtime to avoid the overhead of write barriers and to support partly tag-free garbage collection. The scheme is implemented in the MLKit Standard ML compiler, which generates native x64 machine code. Besides demonstrating a number of important formal properties of the scheme, we measure the scheme’s characteristics, for a number of benchmarks, and compare the performance of the generated executables with the performance of executables generated with the MLton state-of-the-art Standard ML compiler and configurations of the MLKit with and without region inference and generational garbage collection enabled. Although region inference often serves the purpose of generations, combining region inference with generational garbage collection is shown often to be superior to combining region inference with non-generational collection despite the overhead introduced by a larger amount of memory waste, due to region fragmentation.
BRAF Inhibitors Reprogram Cancer-Associated Fibroblasts to Drive Matrix Remodeling and Therapeutic Escape in Melanoma

β-catenin activation in cancer-associated fibroblasts in response to BRAF inhibitors stimulates POSTN secretion to promote resistance in cancer cells, revealing POSTN as a potential matrix target in cancer therapy. The tumor stroma and its cellular components are known to play an important role in tumor response to treatment. Here, we report a novel resistance mechanism in melanoma that is elicited by BRAF inhibitor (BRAFi)–induced noncanonical activation of nuclear β-catenin signaling in cancer-associated fibroblasts (CAF). Treatment with BRAFi leads to an expanded CAF population with increased β-catenin nuclear accumulation and enhanced biological properties. This CAF subpopulation is essential for melanoma cells to proliferate and acquire resistance to BRAFi/MEK inhibitors (MEKi). Mechanistically, BRAFi induces BRAF-CRAF heterodimerization and subsequent activation of ERK signaling in CAFs, leading to inactivation of the β-catenin destruction complex. RNA-seq identified periostin (POSTN) as a major downstream effector of β-catenin in CAFs. POSTN compensates for the loss of β-catenin in CAFs and mediates melanoma cell BRAFi/MEKi resistance. In melanoma cells, POSTN activates phosphoinositide 3-kinase (PI3K)/AKT signaling and subsequently reactivates the ERK pathway that was inhibited by BRAFi/MEKi. Collectively, these data underscore the role of BRAFi-induced CAF reprogramming in matrix remodeling and therapeutic escape of melanoma cells. Significance: β-Catenin activation in cancer-associated fibroblasts in response to BRAF inhibitors stimulates POSTN secretion to promote resistance in cancer cells, revealing POSTN as a potential matrix target in cancer therapy.
Harmonised segmentation of neonatal brain MRI

Deep learning based medical image segmentation has shown great potential in becoming a key part of the clinical analysis pipeline. However, many of these models rely on the assumption that the train and test data come from the same distribution. This means that such methods cannot guarantee high quality predictions when the source and target domains are dissimilar due to different acquisition protocols, or biases in patient cohorts. Recently, unsupervised domain adaptation (DA) techniques have shown great potential in alleviating this problem by minimizing the shift between the source and target distributions, without requiring the use of labelled data in the target domain. In this work, we aim to predict tissue segmentation maps on T2-weighted (T2w) magnetic resonance imaging (MRI) data of an unseen preterm-born neonatal population, which has both different acquisition parameters and population bias when compared to our training data. We achieve this by investigating two unsupervised DA techniques with the objective of finding the best solution for our problem. We compare the two methods with a baseline fully-supervised segmentation network and report our results in terms of Dice scores obtained on our ground truth test dataset. Moreover, we analyse tissue volumes and cortical thickness (CT) measures of the harmonised data on a subset of the population matched for gestational age (GA) at birth and postmenstrual age (PMA) at scan. Finally, we demonstrate the applicability of the harmonised cortical gray matter maps with an analysis comparing term and preterm-born neonates and a proof-of-principle investigation of the association between CT and a language outcome measure.
Monte Carlo simulations of charged platelet systems

Systems of thin platelets are studied by Monte Carlo simulations. The platelets interact by a hard core pair potential and Coulomb interactions associated with a distribution of electrical charges. According to the relative values of the charges localized in the central part and on the periphery of the platelets, it is shown that, at constant density, the system can evolve from an homogeneous fluid phase to a phase where the platelets are associated in clusters which percolate through the simulation cell. We discuss the possibility that this simple model can be a first approximation able to describe qualitatively the behavior of kaolin suspensions when the pH value of these solutions decreases from basic to acid.
Effect of Homebuyer Comment on Green Housing Purchase Intention—Mediation Role of Psychological Distance

Green housing is a new type of building that advocates energy saving and environmental protection. How to stimulate buyers to buy green housing under the background of high cost is the key problem to guide green consumption. First of all, based on the existing literature, the comment of homebuyers was divided into comment quantity, comment quality, comment titer and evaluator credibility. The psychological distance mediation variable was introduced, and three dimensions of time distance, social distance, and space distance were selected to construct the influence model of homebuyer comment on green housing purchase intention. Meanwhile, the concept model was built, and questionnaires were adopted for empirical analysis. On this basis, considering the long-term purchase behavior of buyers, the influence model of homebuyers' second comment on green housing purchase intention with the Hotelling model was established. The results show that comment quality, comment titer, and the credit rating of the evaluator have a positive effect on green housing purchase intention while comment quantity has no significant effect. Psychological distance plays a mediation role between comment quality, comment titer, the credit rating of the evaluator, and green housing purchase intention while having a mediation effect between comment quantity and green housing purchase intention. In the long-term purchase behavior of green housing, psychological distance plays a greater role than price. At last, some suggestions were proposed.
Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection

Vaccine-induced immune responses following immunization with promising Chlamydia vaccines protected experimental animals from Chlamydia-induced upper genital tract pathologies and infertility. In contrast, primary genital infection with live Chlamydia does not protect against these pathologies. We hypothesized that differential miRNA profiles induced in the upper genital tracts (UGT) of mice correlate with the disparate immunity vs. pathologic outcomes associated with vaccine immunization and chlamydial infection. Thus, miRNA expression profiles in the UGT of mice after Chlamydia infection (Live EB) and immunization with dendritic cell (DC)-based vaccine (DC vaccine) or VCG-based vaccine (VCG vaccine) were compared using the NanoString nCounter Mouse miRNA assay. Of the 602 miRNAs differentially expressed (DE) in the UGT of immunized and infected mice, we selected 58 with counts >100 and p-values < 0.05 for further analysis. Interestingly, vaccine immunization and Chlamydia infection induced the expression of distinct miRNA profiles with a higher proportion in vaccine-immunized compared to Chlamydia infected mice; DC vaccine (41), VCG vaccine (23), and Live EB (15). Hierarchical clustering analysis showed notable differences in the uniquely DE miRNAs for each experimental group, with DC vaccine showing the highest number (21 up-regulated, five down-regulated), VCG vaccine (two up-regulated, five down-regulated), and live EB (two up-regulated, four down-regulated). The DC vaccine-immunized group showed the highest number (21 up-regulated and five down-regulated compared to two up-regulated and four down-regulated in the live Chlamydia infected group). Pathway analysis showed that the DE miRNAs target genes that regulate several biological processes and functions associated with immune response and inflammation. These results suggest that the induction of differential miRNA expression plays a significant role in the disparate immunity outcomes associated with Chlamydia infection and vaccination.
Characterization of the CDAA Diet-Induced Non-alcoholic Steatohepatitis Model: Sex-Specific Differences in Inflammation, Fibrosis, and Cholesterol Metabolism in Middle-Aged Mice

Background The prevalence of non-alcoholic steatohepatitis (NASH) rapidly increases with associated metabolic disorders such as dyslipidemia; therefore, NASH is now considered an independent risk factor of cardiovascular diseases. NASH displays sex-linked epidemiological, phenotypical, and molecular differences; however, little is known about the background of these sex-specific differences on the molecular level. Objectives We aimed to assess sex-specific differences in the expression of inflammatory and fibrotic genes, as well as in cholesterol metabolism, focusing on the expression of Pcsk9 in several tissues in a mouse model of NASH that shows the typical features of the human condition. Methods and Results We fed 10-months-old male and female C57Bl/6J mice with a NASH-inducing CDAA or corresponding control diet for 8 weeks. We found that, compared to the control male mice baseline, hepatic Pcsk9 expression as well as serum PCSK9 level was significantly higher in females, and both circulating PCSK9 level and the hepatic Pcsk9 gene were markedly decreased in female mice during NASH development. Histological analysis revealed that male and female mice develop a similar degree of steatosis; however, fibrosis was more pronounced in males upon CDAA diet feeding. Strikingly, female mice have higher hepatic expression of the pro-inflammatory cytokines (Il1b, Ifng), and increased IL-1β cleavage by the NLRP3 inflammasome, and a decrease in Clec4f+ resident Kupffer cell population in comparison to males in the CDAA-fed groups. Conclusion This is the first demonstration that there are critical sex-specific differences during NASH development in middle-aged mice regarding inflammation, fibrosis, and cholesterol metabolism and that changes in PCSK9 and IL-1β are likely important contributors to sex-specific changes during the transition to NASH.
The Intersection of the Genetic Architectures of Orofacial Clefts and Normal Facial Variation

Unaffected relatives of individuals with non-syndromic cleft lip with or without cleft palate (NSCL/P) show distinctive facial features. The presence of this facial endophenotype is potentially an expression of underlying genetic susceptibility to NSCL/P in the larger unselected population. To explore this hypothesis, we first partitioned the face into 63 partially overlapping regions representing global-to-local facial morphology and then defined endophenotypic traits by contrasting the 3D facial images from 264 unaffected parents of individuals with NSCL/P versus 3,171 controls. We observed distinct facial features between parents and controls across 59 global-to-local facial segments at nominal significance (p ≤ 0.05) and 52 segments at Bonferroni corrected significance (p < 1.2 × 10–3), respectively. Next, we quantified these distinct facial features as univariate traits in another dataset of 8,246 unaffected European individuals and performed a genome-wide association study. We identified 29 independent genetic loci that were associated (p < 5 × 10–8) with at least one of the tested endophenotypic traits, and nine genetic loci also passed the study-wide threshold (p < 8.47 × 10–10). Of the 29 loci, 22 were in proximity of loci previously associated with normal facial variation, 18 were near genes that show strong evidence in orofacial clefting (OFC), and another 10 showed some evidence in OFC. Additionally, polygenic risk scores for NSCL/P showed associations with the endophenotypic traits. This study thus supports the hypothesis of a shared genetic architecture of normal facial development and OFC.
Age-Related Changes in Standing Balance in Preschoolers Using Traditional and Nonlinear Methods

Considerable disagreement exists on the linearity of the development of standing balance in children. This study aimed to use different traditional and nonlinear methods to investigate age-related changes in standing balance in preschoolers. A sample of 118 preschoolers took part in this study. A force platform was used to record the center of pressure during standing balance over 15 s in three conditions: eyes open, eyes closed, and/or head extended backward. Detrended fluctuation analysis (DFA), recurrence quantification analysis (RQA), and traditional measures were used to evaluate standing balance. The main results are as follows: (1) Higher range and SD in the anterior-posterior (AP) direction were observed for 5-year-old than for 4-year-old children, while higher DFA coefficient (at shorter time scales) and higher determinism and laminarity in the AP direction were found for 5-year-old children compared to 3- and 4-year-old children; and (2) as sensory conditions became more challenging, all traditional measures increased and DFA coefficients (at shorter and longer time scales) decreased in the AP and mediolateral directions, while determinism and laminarity significantly declined in the AP direction. In conclusion, although increased postural sway, 5-year-old preschool children’s balance performance improved, and their control strategy changed significantly compared with the younger preschoolers. Sensory perturbation (eye closure and/or head extension) changed preschoolers’ balance performance and control strategy. Moreover, both traditional and nonlinear methods provided complementary information on the control of standing balance in preschoolers.
mtDNA Heteroplasmy at the Core of Aging-Associated Heart Failure. An Integrative View of OXPHOS and Mitochondrial Life Cycle in Cardiac Mitochondrial Physiology

The most common aging-associated diseases are cardiovascular diseases which affect 40% of elderly people. Elderly people are prone to suffer aging-associated diseases which are not only related to health and medical cost but also to labor, household productivity and mortality cost. Aging is becoming a world problem and it is estimated that 21.8% of global population will be older than 65 years old in 2050; and for the first time in human history, there will be more elderly people than children. It is well accepted that the origin of aging-associated cardiovascular diseases is mitochondrial dysfunction. Mitochondria have their own genome (mtDNA) that is circular, double-stranded, and 16,569 bp long in humans. There are between 500 to 6000 mtDNA copies per cell which are tissue-specific. As a by-product of ATP production, reactive oxygen species (ROS) are generated which damage proteins, lipids, and mtDNA. ROS-mutated mtDNA co-existing with wild type mtDNA is called mtDNA heteroplasmy. The progressive increase in mtDNA heteroplasmy causes progressive mitochondrial dysfunction leading to a loss in their bioenergetic capacity, disruption in the balance of mitochondrial fusion and fission events (mitochondrial dynamics, MtDy) and decreased mitophagy. This failure in mitochondrial physiology leads to the accumulation of depolarized and ROS-generating mitochondria. Thus, besides attenuated ATP production, dysfunctional mitochondria interfere with proper cellular metabolism and signaling pathways in cardiac cells, contributing to the development of aging-associated cardiovascular diseases. In this context, there is a growing interest to enhance mitochondrial function by decreasing mtDNA heteroplasmy. Reduction in mtDNA heteroplasmy is associated with increased mitophagy, proper MtDy balance and mitochondrial biogenesis; and those processes can delay the onset or progression of cardiovascular diseases. This has led to the development of mitochondrial therapies based on the application of nutritional, pharmacological and genetic treatments. Those seeking to have a positive impact on mtDNA integrity, mitochondrial biogenesis, dynamics and mitophagy in old and sick hearts. This review covers the current knowledge of mitochondrial physiopathology in aging, how disruption of OXPHOS or mitochondrial life cycle alter mtDNA and cardiac cell function; and novel mitochondrial therapies to protect and rescue our heart from cardiovascular diseases.
The Absence of the Transient Receptor Potential Vanilloid 1 Directly Impacts on the Expression and Localization of the Endocannabinoid System in the Mouse Hippocampus

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective ligand-gated cation channel involved in synaptic transmission, plasticity, and brain pathology. In the hippocampal dentate gyrus, TRPV1 localizes to dendritic spines and dendrites postsynaptic to excitatory synapses in the molecular layer (ML). At these same synapses, the cannabinoid CB1 receptor (CB1R) activated by exogenous and endogenous cannabinoids localizes to the presynaptic terminals. Hence, as both receptors are activated by endogenous anandamide, co-localize, and mediate long-term depression of the excitatory synaptic transmission at the medial perforant path (MPP) excitatory synapses though by different mechanisms, it is plausible that they might be exerting a reciprocal influence from their opposite synaptic sites. In this anatomical scenario, we tested whether the absence of TRPV1 affects the endocannabinoid system. The results obtained using biochemical techniques and immunoelectron microscopy in a mouse with the genetic deletion of TRPV1 show that the expression and localization of components of the endocannabinoid system, included CB1R, change upon the constitutive absence of TRPV1. Thus, the expression of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) drastically increased in TRPV1−/− whole homogenates. Furthermore, CB1R and MAGL decreased and the cannabinoid receptor interacting protein 1a (CRIP1a) increased in TRPV1−/− synaptosomes. Also, CB1R positive excitatory terminals increased, the number of excitatory terminals decreased, and CB1R particles dropped significantly in inhibitory terminals in the dentate ML of TRPV1−/− mice. In the outer 2/3 ML of the TRPV1−/− mutants, the proportion of CB1R particles decreased in dendrites, and increased in excitatory terminals and astrocytes. In the inner 1/3 ML, the proportion of labeling increased in excitatory terminals, neuronal mitochondria, and dendrites. Altogether, these observations indicate the existence of compensatory changes in the endocannabinoid system upon TRPV1 removal, and endorse the importance of the potential functional adaptations derived from the lack of TRPV1 in the mouse brain.