Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroscience of Object Relations in Health and Disorder: A Proposal for an Integrative Model

Recent advances in the neuroscience of episodic memory provide a framework to integrate object relations theory, a psychoanalytic model of mind development, with potential neural mechanisms. Object relations are primordial cognitive-affective units of the mind derived from survival- and safety-level experiences with caretakers during phase-sensitive periods of infancy and toddlerhood. Because these are learning experiences, their neural substrate likely involves memory, here affect-enhanced episodic memory. Inaugural object relations are encoded by the hippocampus-amygdala synaptic plasticity, and systems-consolidated by medial prefrontal cortex (mPFC). Self- and object-mental representations, extracted from these early experiences, are at first dichotomized by contradictory affects evoked by frustrating and rewarding interactions (“partial object relations”). Such affective dichotomization appears to be genetically hardwired the amygdala. Intrinsic propensity of mPFC to form schematic frameworks for episodic memories may pilot non-conscious integration of dichotomized mental representations in neonates and infants. With the emergence of working memory in toddlers, an activated self- and object-representation of a particular valence can be juxtaposed with its memorized opposites creating a balanced cognitive-affective frame (conscious “integration of object relations”). Specific events of object relations are forgotten but nevertheless profoundly influence the mental future of the individual, acting (i) as implicit schema-affect templates that regulate attentional priorities, relevance, and preferential assimilation of new information based on past experience, and (ii) as basic units of experience that are, under normal circumstances, integrated as attractors or “focal points” for interactive self-organization of functional brain networks that underlie the mind. A failure to achieve integrated object relations is predictive of poor adult emotional and social outcomes, including personality disorder. Cognitive, cellular-, and systems-neuroscience of episodic memory appear to support key postulates of object relations theory and help elucidate neural mechanisms of psychodynamic psychotherapy. Derived through the dual prism of psychoanalysis and neuroscience, the gained insights may offer new directions to enhance mental health and improve treatment of multiple forms of psychopathology.
Perspectives on ROCK2 as a Therapeutic Target for Alzheimer’s Disease

Rho-associated coiled-coil containing kinase isoform 2 (ROCK2) is a member of the AGC family of serine/threonine kinases and an extensively studied regulator of actin-mediated cytoskeleton contractility. Over the past decade, new evidence has emerged that suggests ROCK2 regulates autophagy. Recent studies indicate that dysregulation of autophagy contributes to the development of misfolded tau aggregates among entorhinal cortex (EC) excitatory neurons in early Alzheimer’s disease (AD). While the accumulation of tau oligomers and fibrils is toxic to neurons, autophagy facilitates the degradation of these pathologic species and represents a major cellular pathway for tau disposal in neurons. ROCK2 is expressed in excitatory neurons and pharmacologic inhibition of ROCK2 can induce autophagy pathways. In this mini-review, we explore potential mechanisms by which ROCK2 mediates autophagy and actin dynamics and discuss how these pathways represent therapeutic avenues for Alzheimer’s disease.
Co-designing Behavior Change Resources With Treatment-Seeking Smokers: Engagement Events' Findings

Background: Primary care organizations are well-suited to help patients change their unhealthy behaviors. Evidence shows that risk communication and self-monitoring of behavior are is an effective strategy practitioners can use to promote health behavior change with their patients. In order for this evidence to be actionable, it is important to understand how patients would like this information to be communicated and to operationalize the self-monitoring resources. The objective of this study was to co-create resources that encourage behavior change based on the scientific evidence and from patients with lived experiences. Materials and Methods: Twenty-seven individuals who participated in a smoking cessation program and engaged in at least one other unhealthy behavior joined one of two engagement events. Each event was 3 h in duration and consisted of two exercises that provided support to participants in reaching a consensus about the types of messages they would like to receive from their practitioner as well as self-monitoring resources they would prefer to use. The first exercise followed an adapted version of the Consensus Methodology developed by the Institute of Cultural Affairs Canada, while the second exercise was in accordance to the Nominal Group Technique. Results: Participants' preference was to have practitioners convey messages to promote health behavior change that include positive affirmation and to monitor all their health behaviors using a single self-reported tracking sheet. Conclusions: This paper features the use of engagement events to reflect upon and identify potential resources that treatment seeking smokers prefer to receive while attempting to modify unhealthy behaviors. These resources can be used by health care providers in primary care settings to support health promotion interventions and assist their patients to increase their likelihood of adopting positive changes to risk behaviors.
Social Avoidance and Social Adjustment: The Moderating Role of Emotion Regulation and Emotion Lability/Negativity Among Chinese Preschool Children

The present study explored the role of emotion regulation and emotion lability/negativity as a moderator in the relation between child social avoidance and social adjustment (i.e., interpersonal skills, asocial behavior, peer exclusion) in Chinese culture. Participants were N = 194 children (102 boys, 92 girls, Mage = 70.82 months, SD = 5.40) recruited from nine classrooms in two public kindergartens in Shanghai, People’s Republic of China. Multi-source assessments were employed with mothers rating children’s social avoidance and teachers rating children’s emotion regulation, emotion lability/negativity and social adjustment outcomes. The results indicated that the relations between social avoidance and social adjustment difficulties were more negative among children lower in emotion regulation, but not significant for children with higher emotion regulation. In contrast, the relations between social avoidance and social adjustment difficulties were more positive among children higher in emotion lability/negativity, but not significant for children with lower emotion lability/negativity. This study informs us about how emotion regulation and emotion lability/negativity are jointly associated with socially avoidant children’s development. As well, the findings highlight the importance of considering the meaning and implication of social avoidance in Chinese culture.
The Influence of the Inconsistent Color Presentation of the Original Price and Sale Price on Purchase Likelihood

Retailers like to use different colors to present the sale price and original price when they are presenting a promotion price. How does the inconsistent color presentation of the prices influence consumers’ purchase likelihood? The extant research does not consider this question. This article will address this question. Drawing on incongruence theory and the persuasion knowledge model (PKM), this article proposes that when the color of the sale price is inconsistent (vs. consistent) with that of the original price, consumers show less preference for the sale price. The reason is that consumers perceive the price as being less trustworthy, which leads to a lower purchase likelihood. Furthermore, this effect is affected by the brand awareness of products. Specifically, when products are less-known brands, the inconsistent (vs. consistent) colors of the sale price and original price will lead to a lower purchase likelihood. In contrast, when products are well-known brands, the inconsistent (vs. consistent) colors of the sale price and original price will lead to a high purchase likelihood. In this article, four studies are used to verify these hypotheses, and implications of theory and practice of the present research are discussed.
Aberrant Temporal-spatial Patterns to Sad expressions in Major Depressive Disorders via Hidden Markov Model

Background The pathological mechanisms of Major depressive disorders (MDD) is associated with over-expressing of negative emotions, and the overall temporal-spatial patterns underlying over-representation in depression still remained to be revealed to date. We hypothesized that the aberrant spatio-temporal attributes of the process of sad expressions relate to MDD and help to detect depression severity. Methods We enrolled a total of 96 subjects including 47 MDDs and 49 healthy controls (HCs), and recorded their Magnetoencephalography data under a sad expressions recognition task. A hidden Markov model (HMM) was applied to separate the whole neural activity into several brain states, then to characterize the dynamics. To find the disrupted spatial-temporal features, power estimations and fractional occupancy of each state were contrasted between MDDs and HCs. Results Three states were found over the period of emotional stimuli processing procedure. The visual state was mainly distributed in early stage (0 - 270ms) and the limbic state in middle and later stage (270ms - 600ms) of the task, while the fronto-parietal state remained a steady proportion across the whole period. MDDs activated statistically more in limbic system during limbic state (p = 0.0045) and less in frontoparietal control network during fronto-parietal state (p = 5.38*10−5) relative to HCs. Hamilton-Depression-Rating Scale scores was significantly correlated with the predicted severity value using the state descriptors (p = 0.0062, r = 0.3933). Discussion As human brain exhibited varied activation patterns under the negative stimuli, MDDs expressed disrupted temporal-spatial activated patterns across varied stages involving the primary visual perception and emotional contents processing compared to HCs, indicting disordered regulation of brain functions. Furthermore, descriptors built by HMM could be potential biomarkers for identifying the severity of depression disorders.
Pool choice in a vertical landscape: Tadpole‐rearing site flexibility in phytotelm‐breeding frogs

Many species of Neotropical frogs have evolved to deposit their tadpoles in small water bodies inside plant structures called phytotelmata. These pools are small enough to exclude large predators but have limited nutrients and high desiccation risk. Here, we explore phytotelm use by three common Neotropical species: Osteocephalus oophagus, an arboreal frog that periodically feeds eggs to its tadpoles; Dendrobates tinctorius, a tadpole-transporting poison frog with cannibalistic tadpoles; and Allobates femoralis, a terrestrial tadpole-transporting poison frog with omnivorous tadpoles. We found that D. tinctorius occupies pools across the chemical and vertical gradient, whereas A. femoralis and O. oophagus appear to have narrower niches that are restricted primarily by pool height, water capacity, alkalinity, and salinity. Dendrobates tinctorius tadpoles are particularly flexible, and can survive in a wide range of chemical, physical, and biological conditions, whereas O. oophagus seems to prefer small, clear pools and A. femoralis occupies medium-sized pools with abundant leaf litter and low salinity. Together, these results show the possible niche partitioning of phytotelmata among frogs, and provide insight into stressors and resilience of phytotelm breeders.
Multiphasic value biases in fast-paced decisions

Perceptual decisions are biased toward higher-value options when overall gains can be improved. When stimuli demand immediate reactions, the neurophysiological decision process dynamically evolves through distinct phases of growing anticipation, detection and discrimination, but how value biases are exerted through these phases remains unknown. Here, by parsing motor preparation dynamics in human electrophysiology, we uncovered a multiphasic pattern of countervailing biases operating in speeded decisions. Anticipatory preparation of higher-value actions began earlier, conferring a “starting point”-advantage at stimulus onset, but the delayed preparation of lower-value actions was steeper, conferring a value-opposed buildup rate bias. This, in turn, was countered by a transient deflection toward the higher value action evoked by stimulus detection. A neurally-constrained process model featuring anticipatory urgency, biased detection, and accumulation of growing stimulus-discriminating evidence, successfully captured both behavior and motor preparation dynamics. Thus, an intricate interplay of distinct biasing mechanisms serves to prioritise time-constrained perceptual decisions.
Neural Correlates of Reactivation and Vividness Reveal Separable Contributions to Objective and Subjective Measures of Episodic Memory

Episodic recollections vary in fidelity, sharpness, and strength—qualities that can be examined using both introspective judgements of mental states and objective measures of brain activity. Subjective and objective measures are both valid ways of “reading out” the content of someone’s internal mnemonic states, each with different strengths and weaknesses. St-Laurent and colleagues (2015) investigated the neural correlates of memory vividness ratings and neural reactivation during memory recall and found considerable overlap, suggesting common neural basis underlying these different markers of successful recollection. Here we extended this work with a much more extensive examination in which we used meta-analytic methods to pool four neuroimaging datasets in order to compare and contrast the neural substrates of neural reactivation and vividness judgements. While reactivation and vividness judgements correlated positively with one another and were associated with common univariate activity in the dorsal attention network and anterior hippocampus, some differences were also observed. Vividness judgments were tied to stronger activation in the striatum and dorsal attention network, together with suppression of default mode network nodes, and we also observed a trend for reactivation to be more closely associated with early visual cortex activity. A mediation analysis found support for the hypothesis that neural reactivation is necessary for vivid recollection, with activity in the anterior hippocampus associated with greater reactivation. Our results suggest that neural reactivation and vividness judgements reflect common recollective processing but differ in the extent to which they engage effortful, attentional processing. Additionally, the similarity between reactivation and vividness appears to arise, partly, through hippocampal processing during recollection.
Tight Junction ZO Proteins Maintain Tissue Fluidity, Ensuring Efficient Collective Cell Migration

Tight junctions are essential components of epithelial tissues connecting neighboring cells to provide protective barriers. Albeit their general function to seal compartments is well understood, their role in collective cell migration is largely unexplored. Here, the importance of the tight junction proteins ZO1 and ZO2 for epithelial migration is investigated employing video microscopy in conjunction with velocimetry, segmentation, cell tracking, and atomic force microscopy/spectroscopy. The results indicate that ZO proteins are necessary for fast and coherent migration. In particular, ZO1 and 2 loss (dKD) induces actomyosin remodeling away from the central cortex towards the periphery of individual cells, resulting in altered viscoelastic properties. A tug-of-war emerges between two subpopulations of cells with distinct morphological and mechanical properties: 1) smaller and highly contractile cells with an outward-bulged apical membrane, and 2) larger, flattened cells, which, due to tensile stress, display a higher proliferation rate. In response, the cell density increases, leading to crowding-induced jamming and more small cells over time. Co-cultures comprising wildtype and dKD cells display phase separation based on differences in contractility rather than differential adhesion. This study shows that ZO proteins are necessary for efficient collective cell migration by maintaining tissue fluidity and controlling proliferation.
Psychomotor impairments and therapeutic implications revealed by a mutation associated with infantile Parkinsonism-Dystonia

Parkinson disease (PD) is a progressive, neurodegenerative disorder affecting over 6.1 million people worldwide. Although the cause of PD remains unclear, studies of highly-penetrant mutations identified in early-onset familial parkinsonism have contributed to our understanding of the molecular mechanisms underlying disease pathology. Dopamine (DA) transporter (DAT) deficiency syndrome (DTDS) is a distinct type of infantile parkinsonism-dystonia that shares key clinical features with PD, including motor deficits (progressive bradykinesia, tremor, hypomimia) and altered DA neurotransmission. Here, we define structural, functional, and behavioral consequences of a Cys substitution at R445 in human DAT (hDAT R445C), identified in a patient with DTDS. We found that this R445 substitution disrupts a phylogenetically conserved intracellular (IC) network of interactions that compromise the hDAT IC gate. This is demonstrated by both Rosetta molecular modeling and fine-grained simulations using hDAT R445C, as well as EPR analysis and X-ray crystallography of the bacterial homolog leucine transporter. Notably, the disruption of this IC network of interactions supported a channel-like intermediate of hDAT and compromised hDAT function. We demonstrate that Drosophila melanogaster expressing hDAT R445C show impaired hDAT activity, which is associated with DA dysfunction in isolated brains and with abnormal behaviors monitored at high-speed time resolution. We show that hDAT R445C Drosophila exhibit motor deficits, lack of motor coordination (i.e. flight coordination) and phenotypic heterogeneity in these behaviors that is typically associated with DTDS and PD. These behaviors are linked with altered dopaminergic signaling stemming from loss of DA neurons and decreased DA availability. We rescued flight coordination through enhanced DAT surface expression via the lysosomal inhibitor chloroquine. Together, these studies shed light on how a DTDS-linked DAT mutation underlies DA dysfunction and, more broadly, the clinical phenotypes shared by DTDS and PD.
A conserved BAH module within mammalian BAHD1 connects H3K27me3 to Polycomb gene silencing

Trimethylation of histone H3 lysine 27 (H3K27me3) is important for gene silencing and imprinting, (epi)genome organization and organismal development. In a prevalent model, the functional readout of H3K27me3 in mammalian cells is achieved through the H3K27me3-recognizing chromodomain harbored within the chromobox (CBX) component of canonical Polycomb repressive complex 1 (cPRC1), which induces chromatin compaction and gene repression. Here, we report that binding of H3K27me3 by a Bromo Adjacent Homology (BAH) domain harbored within BAH domain-containing protein 1 (BAHD1) is required for overall BAHD1 targeting to chromatin and for optimal repression of the H3K27me3-demarcated genes in mammalian cells. Disruption of direct interaction between BAHD1BAH and H3K27me3 by point mutagenesis leads to chromatin remodeling, notably, increased histone acetylation, at its Polycomb gene targets. Mice carrying an H3K27me3-interaction-defective mutation of Bahd1BAH causes marked embryonic lethality, showing a requirement of this pathway for normal development. Altogether, this work demonstrates an H3K27me3-initiated signaling cascade that operates through a conserved BAH “reader” module within BAHD1 in mammals. Key Points BAHD1BAH is a functionally validated mammalian “reader” of H3K27me3, mediating BAHD1 targeting for gene silencing. BAHD1BAH connects H3K27me3 together with histone deacetylation, an integral step of gene silencing. BAHD1BAH-mediated functional readout of H3K27me3 is essential for organismal development. Graphic abstract A mammalian H3K27me3-transduction pathway operates through an H3K27me3-specific ‘reader’ module (BAH) of BAHD1, which assembles a complex with corepressors (HDACs and others) for suppressing histone acetylation and repressing expression at Polycomb target genes.
Control of parallel hippocampal output pathways by amygdalar long-range inhibition

Projections from the basal amygdala (BA) to the ventral hippocampus (vH) are proposed to provide information about the rewarding or threatening nature of learned associations to support appropriate goal-directed and anxiety-like behaviour. Such behaviour occurs via the differential activity of multiple, parallel populations of pyramidal neurons in vH that project to distinct downstream targets, but the nature of BA input and how it connects with these populations is unclear. Using channelrhodopsin-2-assisted circuit mapping in mice, we show that BA input to vH consists of both excitatory and inhibitory projections. Excitatory input specifically targets BA- and nucleus accumbens-projecting vH neurons, and avoids prefrontal cortex-projecting vH neurons; while inhibitory input preferentially targets BA-projecting neurons. Through this specific connectivity, BA inhibitory projections gate place-value associations by controlling the activity of nucleus accumbens-projecting vH neurons. Our results define a parallel excitatory and inhibitory projection from BA to vH that can support goal-directed behaviour.
Assessing the effectiveness of oxathiapiprolin toward Phytophthora agathidicida, the causal agent of kauri dieback disease

Phytophthora species cause disease and devastation of plants in ecological and horticultural settings worldwide. A recently identified species, P. agathidicida, infects and ultimately kills the treasured kauri trees that are endemic to New Zealand. Currently there are few options for controlling or treating P. agathidicida. In this study, we sought to assess the toxicity of the oomycide oxathiapiprolin against several lifecycle stages of two geographically distinct P. agathidicida isolates. Half maximal effective concentration (EC50) values were determined to be approximately 0.1 ng/ml for inhibiting mycelial growth, indicating that P. agathidicida mycelia are more sensitive to oxathiapiprolin than those from most other Phytophthora species that have been studied. Oxathiapiprolin was also highly effective at inhibiting the germination of zoospores (EC50 = 2-9 ng/ml for the two isolates) and oospores (complete inhibition at 100 ng/ml). In addition, oxathiapiprolin delayed the onset of detached kauri leaf infection in a dose-dependent manner. Collectively, the results presented here highlight the significant potential of oxathiapiprolin as a tool to aid in the control of kauri dieback disease.