Miracle-dz/UniFAR-FTUs huggingface dataset:
Fatty Alcohols, a Minor Component of the Tree Tobacco Surface Wax, Reduce Insect Herbivory

Despite decades of research resulting in a comprehensive understanding of epicuticular wax biosynthesis and metabolism, the function of these almost ubiquitous metabolites in plant-herbivore interactions remains unresolved. To develop a better understanding of this role, we investigated plant-herbivore interactions in four Nicotiana glauca (tree tobacco) genome edited mutants. This included [eceriferum1 (cer1), eceriferum3 (cer3), β-ketoacyl-coA synthase6 (kcs6), and fatty acyl-coA reductase (far)] displaying a wide range of alkane and fatty alcohol abundances. Three interaction classes were examined: chewing herbivory with seven caterpillar and one snail species, phloem feeding with Myzus persicae (green peach aphid), and egg laying with Bemisia tabaci (sweet potato whitefly). We found that high wax load and alkane abundance did not reduce caterpillar or snail herbivory. However, fatty alcohol content was negatively correlated with caterpillar growth, suggesting a role in reducing insect herbivory despite its lower levels. Aphid reproduction and feeding activity were not correlated with wax load and composition but are potentially affected by altered cutin composition of cer1 mutants. When examining non-feeding activities, wax crystal morphology could explain the preference of B. tabaci to lay eggs on wildtype plants relative to cer1 and far mutants. Accordingly, the fatty alcohol wax component reduces caterpillar herbivory on the chemical level, but oviposition is increased when wax crystals are dense. The results suggest that this varied response between herbivore classes and species, at times displaying increased and at times reduced fitness in response to altered wax composition is in part a consequence of co-evolution that shaped the specific effects of different N. glauca metabolites such as anabasine and fatty alcohols in plant-herbivore interactions.
Tuned to Learn: An anticipatory hippocampal convergence state conducive to memory formation revealed during midbrain activation

The hippocampus has been a focus of memory research since H.M’s surgery in 1953 abolished his ability to form new memories, yet its mechanistic role in memory is still debated. Here, we identify a novel, systems-level candidate memory mechanism: an anticipatory hippocampal “convergence state”, observed while awaiting valuable information, that both predicts later memory, and accounts for the relationship between midbrain activation and enhanced learning. To reveal this state, we leveraged endogenous neuromodulation associated with motivation: During fMRI, participants viewed trivia questions eliciting high or low curiosity, each followed seconds later by its answer. We reasoned that memory encoding success requires a convergence of factors, and as such, hippocampal states associated with remembered trials would be less variable than forgotten ones. Using a novel multivariate approach, we measured convergence by quantifying the typicality of spatially distributed patterns. We found that during anticipation of trivia answers, hippocampal states showed greater convergence under high than low curiosity. Crucially, convergence in the hippocampus increased with greater midbrain activation and uniquely accounted for the association between midbrain activation and subsequent memory recall. We propose that this novel convergence state in the hippocampus reflects a mechanism of its contribution to long term memory formation and that engagement of this convergence state completes the cascade from motivation to midbrain activity to memory enhancement.
Gambling environment exposure increases temporal discounting but improves model-based control in regular slot-machine gamblers

Gambling disorder is a behavioral addiction that negatively impacts personal finances, work, relationships and mental health. In this pre-registered study (https://osf.io/5ptz9/? view_only=62956a2afcd1495984db4be18c54b50a) we investigated the impact of real-life gambling environments on two computational markers of addiction, temporal discounting and model-based reinforcement learning. Gambling disorder is associated with increased temporal discounting and reduced model-based learning. Regular gamblers (n = 30, DSM-5 score range 3-9) performed both tasks in a neutral (café) and a gambling-related environment (slot-machine venue) in counterbalanced order. Data were modeled using drift diffusion models for temporal discounting and reinforcement learning via hierarchical Bayesian estimation. Replicating previous findings, gamblers discounted rewards more steeply in the gambling-related context. This effect was positively correlated with gambling related cognitive distortions (pre-registered analysis). In contrast to our pre-registered hypothesis, model-based reinforcement learning was improved in the gambling context. Here we show that temporal discounting and model-based reinforcement learning are modulated in opposite ways by real-life gambling cue exposure. Results challenge aspects of habit theories of addiction, and reveal that laboratory-based computational markers of psychopathology are under substantial contextual control.
Identification of Leptospiral Protein Antigens Recognized by WC1+ γδ T Cell Subsets as Target for Development of Recombinant Vaccines

Pathogenic Leptospira species cause leptospirosis, a neglected zoonotic disease recognized as a global public health problem. It is also the cause of the most common cattle infection that results in major economic losses due to reproductive problems. γδ T cells play a role in the protective immune response in livestock species against Leptospira, while human γδ T cells also respond to Leptospira. ABSTRACT Pathogenic Leptospira species cause leptospirosis, a neglected zoonotic disease recognized as a global public health problem. It is also the cause of the most common cattle infection that results in major economic losses due to reproductive problems. γδ T cells play a role in the protective immune response in livestock species against Leptospira, while human γδ T cells also respond to Leptospira. Thus, activation of γδ T cells has emerged as a potential component in the optimization of vaccine strategies. Bovine γδ T cells proliferate and produce gamma interferon (IFN-γ) in response to vaccination with inactivated leptospires, and this response is mediated by a specific subpopulation of the WC1-bearing γδ T cells. WC1 molecules are members of the group B scavenger receptor cysteine-rich (SRCR) superfamily and are composed of multiple SRCR domains, of which particular extracellular domains act as ligands for Leptospira. Since WC1 molecules function as both pattern recognition receptors and γδ TCR coreceptors, the WC1 system has been proposed as a novel target to engage γδ T cells. Here, we demonstrate the involvement of leptospiral protein antigens in the activation of WC1+ γδ T cells and identify two leptospiral outer membrane proteins able to interact directly with them. Interestingly, we show that the protein-specific γδ T cell response is composed of WC1.1+ and WC1.2+ subsets, although a greater number of WC1.1+ γδ T cells respond. Identification of protein antigens will enhance our understanding of the role γδ T cells play in the leptospiral immune response and in recombinant vaccine development.
The interplay of RNA:DNA hybrid structure and G-quadruplexes determines the outcome of R-loop-replisome collisions

R-loops are a major source of genome instability associated with transcription-induced replication stress. However, how R-loops inherently impact replication fork progression is not understood. Here, we characterize R-loop-replisome collisions using a fully reconstituted eukaryotic DNA replication system. We find that RNA:DNA hybrids and G-quadruplexes at both co-directional and head-on R-loops can impact fork progression by inducing fork stalling, uncoupling of leading strand synthesis from replisome progression, and nascent strand gaps. RNase H1 and Pif1 suppress replication defects by resolving RNA:DNA hybrids and G-quadruplexes, respectively. We also identify an intrinsic capacity of replisomes to maintain fork progression at certain R-loops by unwinding RNA:DNA hybrids, repriming leading strand synthesis downstream of G-quadruplexes, or utilizing R-loop transcripts to prime leading strand restart during co-directional R-loop-replisome collisions. Collectively, the data demonstrates that the outcome of R-loop-replisome collisions is modulated by R-loop structure, providing a mechanistic basis for the distinction of deleterious from non-deleterious R-loops.
c-Jun N-terminal kinase (JNK) signaling contributes to cystic burden in polycystic kidney disease

Polycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people. It primarily is caused by mutations in the transmembrane proteins polycystin-1 (Pkd1) and polycystin-2 (Pkd2). The most proximal effects of Pkd mutations leading to cyst formation are not known, but pro-proliferative signaling must be involved for the tubule epithelial cells to increase in number over time. The c-Jun N-terminal kinase (JNK) pathway promotes proliferation and is activated in acute and chronic kidney diseases. Using a mouse model of cystic kidney disease caused by Pkd2 loss, we observe JNK activation in cystic kidneys and observe increased nuclear phospho c-Jun in cystic epithelium. Genetic removal of Jnk1 and Jnk2 suppresses the nuclear accumulation of phospho c-Jun, reduces proliferation and reduces the severity of cystic disease. While Jnk1 and Jnk2 are thought to have largely overlapping functions, we find that Jnk1 loss is nearly as effective as the double loss of Jnk1 and Jnk2. Jnk pathway inhibitors are in development for neurodegeneration, cancer, and fibrotic diseases. Our work suggests that the JNK pathway should be explored as a therapeutic target for ADPKD. Author Summary Autosomal dominant polycystic kidney disease is a leading cause of end stage renal disease requiring dialysis or kidney transplant. During disease development, the cells lining the kidney tubules proliferate. This proliferation transforms normally small diameter tubules into fluid-filled cysts that enlarge with time, eventually destroying all kidney function. Despite decades of research, polycystic kidney disease remains incurable. Furthermore, the precise signaling events involved in cyst initiation and growth remain unclear. The c-Jun N-terminal kinase (JNK), is a major pathway regulating cellular proliferation and differentiation but its importance to polycystic kidney disease was not known. We show that JNK activity is elevated in cystic kidneys and that reducing JNK activity decreases cyst growth pointing to JNK inhibition as a therapeutic strategy for treating polycystic kidney disease.
Synaptic decline precedes dopaminergic neuronal loss in human midbrain organoids harboring a triplication of the SNCA gene

Increased levels of the protein alpha-synuclein (α-syn) are associated with the development of neurodegenerative diseases like Parkinson’s disease (PD). In physiological conditions, α-syn modulates synaptic plasticity, neurogenesis and neuronal survival. However, its pathogenic accumulation and aggregation results in toxicity and neurodegeneration. Here, we used a PD patient specific midbrain organoid model derived from induced pluripotent stem cells harboring a triplication in the SNCA gene to study PD-associated phenotypes. The model recapitulates the two main hallmarks of PD, which are α-syn aggregation and loss of dopaminergic neurons. Additionally, impairments in astrocyte differentiation were detected. Transcriptomics data indicate that synaptic function is impaired in PD specific midbrain organoids. This is further confirmed by alterations in synapse number and electrophysiological activity. We found that synaptic decline precedes neurodegeneration. Finally, this study substantiates that patient specific midbrain organoids allow a personalized phenotyping, which make them an interesting tool for precision medicine and drug discovery.
Analyses of the Factor Structure and Item Measurement Bias of a School Climate Scale in Chilean Students

School Climate is an essential aspect in every school community. It relates to perceptions of the school environment experienced by various members of the educational system. Research has shown that an appropriate school climate impacts not only on the quality of life of all members in the educational system, but also on learning outcomes and education improvements. This study aims to explore a measure of School Climate on Chilean students. A sample of 176,126 10th grade students was used to investigate the factor structure of the items composing the School Climate construct, and to evaluate the potential presence of Differential Item Functioning between male and female groups. Both explanatory and confirmatory factor analysis as well as Rasch models were used to analyze the scale. Differential item functioning between male and female groups was investigated using the Langer-improved Wald test. The results indicated a multidimensional structure of the School Climate construct and that measurement bias for male and female groups exist in some of the items measuring the construct.
Epigenetics as a Mechanism of Developmental Embodiment of Stress, Resilience, and Cardiometabolic Risk Across Generations of Latinx Immigrant Families

Psychosocial stressors can become embodied to alter biology throughout the life course in ways that may have lasting health consequences. Immigrants are particularly vulnerable to high burdens of stress, which have heightened in the current sociopolitical climate. This study is an investigation of how immigration-related stress (IRS) may impact the cardiometabolic risk and epigenetic markers of Latinx immigrant mothers and children in Nashville, TN. We compared stress and resilience factors reported by Latina immigrant mothers and their children (aged 5–13) from two time points spanning the 2016 U.S. presidential election (June 2015–June 2016 baseline, n = 81; March–September 2018 follow-up, n = 39) with cardiometabolic risk markers (BMI, waist circumference, and blood pressure). We also analyzed these factors in relation to DNA methylation in saliva of stress-related candidate genes (SLC6A4 and FKBP5), generated via bisulfite pyrosequencing (complete case n's range from 67–72 baseline and 29–31 follow-up) (n's range from 80 baseline to 36 follow-up). We found various associations with cardiometabolic risk, such as higher social support and greater acculturation were associated with lower BMI in mothers; discrimination and school stress associated with greater waist circumferences in children. Very few exposures associated with FKBP5, but various stressors associated with methylation at many sites in SLC6A4, including immigrant-related stress in both mothers and children, and fear of parent deportation in children. Additionally, in the mothers, total maternal stress, health stress, and subjective social status associated with methylation at multiple sites of SLC6A4. Acculturation associated with methylation in mothers in both genes, though directions of effect varied over time. We also find DNA methylation at SLC6A4 associates with measures of adiposity and blood pressure, suggesting that methylation may be on the pathway linking stress with cardiometabolic risk. More research is needed to determine the role of these epigenetic differences in contributing to embodiment of stress across generations.
Localizing Global Solidarity: Humanitarian Aid in Lesvos

The so-called “refugee crisis” in Lesvos, Greece provides a poignant example of situated, local suffering that has called for the coordination of global resources to provide relief. Some of the first to respond were local and international Citizen Initiatives for Global Solidarity (CIGS). While a growing role for CIGS has been interpreted as a call for more global involvement, arguments for the increased localization of relief efforts suggest the need for aid agents to maintain a reflexive awareness of the potential for an influx of outside assistance to disempower those most affected. We argue that barriers to implementing the localization of humanitarian aid can be better understood by positioning this localization alongside theories of global solidarity. This paper pairs theoretical contributions from the fields of moral and political philosophy with an analysis of interview material gathered in Lesvos between 2015 and 2019. Our goal is to use narratives of conflicting interests in Lesvos to explore conceptual distinctions concerning solidarity and emphasize the importance of the localization of global solidarity in humanitarian aid. We conclude that while global solidarity represents a demanding effort to identify with distant others and provide aid, the intensity and transformative potential of the process of “making the crisis one’s own” through solidary engagement can overshadow the importance of local ownership of crisis management.
Career Planning in Elite Soccer: The Mediating Role of Self-Efficacy, Career Goals, and Athletic Identity

This study proposed a model to examine the role of self-efficacy, career goals, and athletic identity (AI) on the career planning of elite soccer players. Two hundred and eighty-one elite soccer players (males) participated in this study. Means, SD, and bivariate correlations were calculated for the variables under analysis. The hypothesized effect of self-efficacy, career goals, and AI on career planning was tested using structural equation modeling (SEM). Results supported the adequacy of the proposed model in explaining the career planning. Career planning is positively influenced by the level of self-efficacy of players through the definition of career goals and is negatively influenced by the level of AI. At the same time, the self-efficacy of players through the definition of career goals positively influenced AI. These findings reinforce the important role of self-efficacy and career goals for the development of AI and career planning and at the same time the opposite relationship between AI and career planning. Thus, it is suggested that a balance on AI, maintaining high levels of self-efficacy and career goals, is required to improve the process of career planning and retirement.
Biliary Neuroendocrine Neoplasms: Analysis of Prognostic Factors and Development and Validation of a Nomogram

Background For this study, we explored the prognostic profiles of biliary neuroendocrine neoplasms (NENs) patients and identified factors related to prognosis. Further, we developed and validated an effective nomogram to predict the overall survival (OS) of individual patients with biliary NENs. Methods We included a total of 446 biliary NENs patients from the SEER database. We used Kaplan-Meier curves to determine survival time. We employed univariate and multivariate Cox analyses to estimate hazard ratios to identify prognostic factors. We constructed a predictive nomogram based on the results of the multivariate analyses. In addition, we included 28 biliary NENs cases from our center as an external validation cohort. Results The median survival time of biliary NENs from the SEER database was 31 months, and the value of gallbladder NENs (23 months) was significantly shorter than that of the bile duct (45 months) and ampulla of Vater (33.5 months, p=0.023). Multivariate Cox analyses indicated that age, tumor size, pathological classification, SEER stage, and surgery were independent variables associated with survival. The constructed prognostic nomogram demonstrated good calibration and discrimination C-index values of 0.783 and 0.795 in the training and validation dataset, respectively. Conclusion Age, tumor size, pathological classification, SEER stage, and surgery were predictors for the survival of biliary NENs. We developed a nomogram that could determine the 3-year and 5-year OS rates. Through validation of our central database, the novel nomogram is a useful tool for clinicians in estimating individual survival among biliary NENs patients.
Does Day-to-Day Variability in Stool Consistency Link to the Fecal Microbiota Composition?

Introduction Stool consistency has been associated with fecal microbial composition. Stool consistency often varies over time, in subjects with and without gastrointestinal disorders, raising the question whether variability in the microbial composition should be considered in microbiota studies. We evaluated within-subject day-to-day variability in stool consistency and the association with the fecal microbiota in irritable bowel syndrome (IBS) and healthy subjects, over seven days. Methods Twelve IBS patients and 12 healthy subjects collected fecal samples during seven consecutive days. Stool consistency was determined by the patient-reported Bristol Stool Scale (BSS) and fecal dry weight percentage. 16S rRNA V4 gene sequencing was performed and microbial richness (alpha diversity; Chao1 index, observed number of species, effective Shannon index) and microbial community structure (beta diversity; Bray-Curtis distance, generalized UniFrac, and taxa abundance on family level) were determined. Results Linear mixed-effects models showed significant associations between stool consistency and microbial richness, but no time effect. This implies that between-subject but not within-subject variation in microbiota over time can partially be explained by variation in stool consistency. Redundancy analysis showed a significant association between stool consistency and microbial community structure, but additional linear mixed-effects models did not demonstrate a time effect on this. Conclusion This study supports an association between stool consistency and fecal microbiota, but no effect of day-to-day fluctuations in stool consistency within seven days. This consolidates the importance of considering stool consistency in gut microbiota research, though confirms the validity of single fecal sampling to represent an individual’s microbiota at a given time point. NCT00775060.
Optical Absorption and Reflectivity of Four 2D Materials: MoS2, MoP2, NbS2, and NbP2

We calculated the energy band structure and the optical absorption and reflectivity for each of the ultrathin 2D hexagonal materials MoS2, MoP2, NbS2, and NbP2. Our simulations included density functional theory, generalized gradient approximation (GGA), and the Quantum Espresso code. Other researchers already synthesized the first three materials. We obtained that NbP2 should be another hexagonal 2D material. In all cases in the infrared and visible ranges, the absorptions present much larger concerning graphene. However, the absorptions for MoP2, NbP2, and NbS2, are far more prominent concerning MoS2. In the ultraviolet region, the absorptions are like each other and differ from graphene. In all cases, the reflectivities are similar to each other and vary from graphene.