Asymmetric segregation of maternal mRNAs and germline-related determinants in Cephalochordate embryos: implications for the evolution of early patterning events in chordates.

How animal embryos determine their early cell fates is an important question in developmental biology. In various model animals asymmetrically localized maternal transcripts play important roles in axial patterning and cell fate specification. Cephalochordates (amphioxus), which have three living genera (Asymmetron, Epigonichthys, Branchiostoma), are an early branching chordate lineage and thus occupy a key phylogenetic position for understanding the evolution of chordate developmental mechanisms. It has been shown that in the zygote of Brachiostoma amphioxus, which possess bilateral gonads flanking both sides of their trunk region, maternal transcripts of germline determinants form a compact granule. During early embryogenesis this granule is inherited by a single blastomere that subsequently gives rise to a cluster of cells displaying typical characteristics of primordial germ cells (PGC). These PGCs then come to lie in the tailbud region and proliferate during posterior elongation of the larva to join in the gonad anlagen at the ventral tip of the developing myomeres in amphioxus larvae. However, in Asymmetron and Epigonichthys amphioxus, whose gonads are present only on the right side of their body, nothing is known about their PGC development or the cellular/morphogenetic processes resulting in the asymmetric distribution of gonads. Using conserved germline determinants as markers, we show that similarly to Brachiostoma amphioxus, Asymmetron also employ a preformation mechanism to specify their PGCs, suggesting that this mechanism represents an ancient trait dating back to the common ancestor of Cephalochordates. Surprisingly, we found that Asymmetron PGCs are initially deposited on both sides of the body during early larval development; however, the left side PGCs cease to exist in young juveniles, suggesting that PGCs are eliminated from the left body side during larval development or following metamorphosis. This is reminiscent of the PGC development in the sea urchin embryo, and we discuss the implications of this observation for the evolution of developmental mechanisms.

Hippocampal subfields and thalamic nuclei associations with clinical outcomes in multiple sclerosis: An ultrahigh field MRI study.

BACKGROUND: Previous studies have shown that thalamic and hippocampal neurodegeneration is associated with clinical decline in Multiple Sclerosis (MS). However, contributions of the specific thalamic nuclei and hippocampal subfields require further examination. OBJECTIVE: Using 7 Tesla (7T) magnetic resonance imaging (MRI), we investigated the cross-sectional associations between functionally grouped thalamic nuclei and hippocampal subfields volumes and T1 relaxation times (T1-RT) and subsequent clinical outcomes in MS. METHODS: High-resolution T1-weighted and T2-weighted images were acquired at 7T (n=31), preprocessed, and segmented using the Thalamus Optimized Multi Atlas Segmentation (THOMAS, for thalamic nuclei) and the Automatic Segmentation of Hippocampal Subfields (ASHS, for hippocampal subfields) packages. We calculated Pearson correlations between hippocampal subfields and thalamic nuclei volumes and T1-RT and subsequent multi-modal rater-determined and patient-reported clinical outcomes (∼2.5 years after imaging acquisition), correcting for confounders and multiple tests. RESULTS: Smaller volume bilaterally in the anterior thalamus region correlated with worse performance in gait function, as measured by the Patient Determined Disease Steps (PDDS). Additionally, larger volume in most functional groups of thalamic nuclei correlated with better visual information processing and cognitive function, as measured by the Symbol Digit Modalities Test (SDMT). In bilateral medial and left posterior thalamic regions, there was an inverse association between volumes and T1-RT, potentially indicating higher tissue degeneration in these regions. We also observed marginal associations between the right hippocampal subfields (both volumes and T1-RT) and subsequent clinical outcomes, though they did not survive correction for multiple testing. CONCLUSION: Ultrahigh field MRI identified markers of structural damage in the thalamic nuclei associated with subsequently worse clinical outcomes in individuals with MS. Longitudinal studies will enable better understanding of the role of microstructural integrity in these brain regions in influencing MS outcomes.

Linking childhood trauma to the psychopathology of schizophrenia: the role of oxytocin.

Childhood trauma has been linked to schizophrenia, but underlying biological mechanisms remain elusive. This study explored the potential role of plasma oxytocin as a mediator in the relationship between childhood trauma and the psychopathology of schizophrenia. 160 patients with schizophrenia and 80 age- and sex-matched healthy controls were assessed for childhood trauma experiences using the Childhood Trauma Questionnaire and structured interviews. Psychopathology was evaluated using the Positive and Negative Syndrome Scale and plasma oxytocin levels were measured. Results showed that patients with schizophrenia had lower oxytocin levels and higher childhood trauma scores than healthy controls. There was a significant correlation between childhood trauma scores and psychopathology, with plasma oxytocin levels being inversely associated with psychopathology, except for positive symptoms. Hierarchical regression analysis indicated that both childhood trauma scores and plasma oxytocin levels significantly predicted psychopathology. Plasma oxytocin levels partially mediated the relationship between childhood trauma and schizophrenia psychopathology. This study underscores the potential role of oxytocin in bridging the gap between childhood trauma and schizophrenia.

Association between serum multi-protein biomarker profile and real-world disability in multiple sclerosis.

Few studies examined blood biomarkers informative of patient-reported outcome (PRO) of disability in people with multiple sclerosis (MS). We examined the associations between serum multi-protein biomarker profiles and patient-reported MS disability. In this cross-sectional study (2017-2020), adults with diagnosis of MS (or precursors) from two independent clinic-based cohorts were divided into a training and test set. For predictors, we examined seven clinical factors (age at sample collection, sex, race/ethnicity, disease subtype, disease duration, disease-modifying therapy [DMT], and time interval between sample collection and closest PRO assessment) and 19 serum protein biomarkers potentially associated with MS disease activity endpoints identified from prior studies. We trained machine learning (ML) models (Least Absolute Shrinkage and Selection Operator regression [LASSO], Random Forest, Extreme Gradient Boosting, Support Vector Machines, stacking ensemble learning, and stacking classification) for predicting Patient Determined Disease Steps (PDDS) score as the primary endpoint and reported model performance using the held-out test set. The study included 431 participants (mean age 49 years, 81% women, 94% non-Hispanic White). For binary PDDS score, combined feature input of routine clinical factors and the 19 proteins consistently outperformed base models (comprising clinical features alone or clinical features plus one single protein at a time) in predicting severe (PDDS ≥ 4) versus mild/moderate (PDDS < 4) disability across multiple machine learning approaches, with LASSO achieving the best area under the curve (AUCPDDS = 0.91) and other metrics. For ordinal PDDS score, LASSO model comprising combined clinical factors and 19 proteins as feature input (R2PDDS = 0.31) again outperformed base models. The two best-performing LASSO models (i.e., binary and ordinal PDDS score) shared six clinical features (age, sex, race/ethnicity, disease subtype, disease duration, DMT efficacy) and nine proteins (cluster of differentiation 6, CUB-domain-containing protein 1, contactin-2, interleukin-12 subunit-beta, neurofilament light chain [NfL], protogenin, serpin family A member 9, tumor necrosis factor superfamily member 13B, versican). By comparison, LASSO models with clinical features plus one single protein at a time as feature input did not select either NfL or glial fibrillary acidic protein (GFAP) as a final feature. Forcing either NfL or GFAP as a single protein feature into models did not improve performance beyond clinical features alone. Stacking classification model using five functional pathways to represent multiple proteins as meta-features implicated those involved in neuroaxonal integrity as significant contributors to predictive performance. Thus, serum multi-protein biomarker profiles improve the prediction of real-world MS disability status beyond clinical profile alone or clinical profile plus single protein biomarker, reaching clinically actionable performance.

Negative emotionality downregulation affects moral choice but not moral judgement of harm: a pharmacological study.

Previous neuroscientific research has expounded on the fundamental role played by emotion during moral decision-making. Negative emotionality has been observed to exert a general inhibitory effect towards harmful behaviors against others. Nevertheless, the downregulation of negative affects at different levels of moral processing (e.g. impersonal versus personal moral dilemmas) alongside its possible interactions with other factors (e.g. perspective taking) hasn't been directly assessed; both of which can assist in predicting future moral decision-making. In the present research, we empirically test (Study 1, N = 41) whether downregulating negative emotionality through pharmacological interventions using lorazepam (a GABA receptor agonist), modulate the permissibility of harm to others -i.e. if participants find it more morally permissible to harm others when harm is unavoidable (inevitable harm moral dilemmas), than when it may be avoided (evitable harm moral dilemmas). Furthermore, using another sample (Study 2, N = 31), we assess whether lorazepam's effect is modulated by different perspective-taking conditions during a moral dilemma task -e.g. "is it morally permissible for you to […]?" (1st person perspective), relative to "is it morally permissible for [x individual] to […]?" (3rd person perspective)-, where the outcome of the different scenarios is controlled. The results of both studies converge, revealing an emotion-dependent, rather than an outcome-dependent, pharmacological modulation. Lorazepam only influenced interpersonal moral judgments when not modulated by the evitable/inevitable condition. Furthermore, there was a significant interaction between perspective-taking and drug administration, as lorazepam exerted a larger effect in modulating moral choices rather than moral judgements.

A sensory signature of unaffected biological parents predicts the risk of autism in their offspring.

AIM: Despite the emphasis on sensory dysfunction phenotypes in the revised diagnostic criteria for autism spectrum disorder (ASD), there has been limited research, particularly in the field of neurobiology, investigating the concordance in sensory features between individuals with ASD and their genetic relatives. Therefore, our objective was to examine whether neurobehavioral sensory patterns could serve as endophenotypic markers for ASD. METHODS: We combined questionnaire- and lab-based sensory evaluations with sensory fMRI measures to examine the patterns of sensory responsivity in 30 clinically diagnosed with ASD, 26 matched controls (CON), and 48 biological parents for both groups (27 parents of individuals with ASD [P-ASD] and 21 for individuals with CON [P-CON]). RESULTS: The ASD and P-ASD groups had higher sensory responsivity and rated sensory stimuli as more unpleasant than the CON and P-CON groups, respectively. They also exhibited greater hemodynamic responses within the sensory cortices. Overlapping activations were observed within these sensory cortices in the ASD and P-ASD groups. Using a machine learning approach with robust prediction models across cohorts, we demonstrated that the sensory profile of biological parents accurately predicted the likelihood of their offspring having ASD, achieving a prediction accuracy of 71.4%. CONCLUSIONS: These findings provide support for the hereditary basis of sensory alterations in ASD and suggest a potential avenue to improve ASD diagnosis by utilizing the sensory signature of biological parents, especially in families with a high risk of ASD. This approach holds promising prospects for early detection, even before the birth of the offspring.

The interplay of childhood trauma, oxytocin, and impulsivity in predicting the onset of methamphetamine use.

BACKGROUND: Childhood trauma is associated with substance use disorders, including methamphetamine use disorder (MUD). Oxytocin, involved in social bonding, stress regulation, and reward processing, may influence addiction vulnerability and impulsivity in individuals with a history of childhood trauma. OBJECTIVE: To investigate the relationships among childhood trauma, oxytocin levels, impulsivity, and the age of first methamphetamine use in individuals with MUD. PARTICIPANTS AND SETTING: The study included 298 male participants (148 individuals with MUD and 150 healthy controls) from both probation offices and psychiatric clinics. METHODS: Childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF), impulsivity with the Barratt Impulsiveness Scale-11 (BIS-11), and plasma oxytocin levels were obtained. RESULTS: Individuals with MUD exhibited higher levels of childhood trauma, impulsivity, and lower plasma oxytocin levels compared to healthy controls. Childhood trauma was associated with a younger age of first methamphetamine use, higher impulsivity, and lower oxytocin levels among individuals with MUD. Plasma oxytocin levels partially mediated the relationship between childhood trauma and both the age of first methamphetamine use and impulsivity. Serial mediation analysis demonstrated that oxytocin levels and impulsivity sequentially mediated the relationship between childhood trauma and the age of first methamphetamine use. CONCLUSIONS: The findings reveal the complex interplay among childhood trauma, oxytocin, impulsivity, and methamphetamine use, emphasizing the importance of considering these factors in prevention and intervention strategies for MUD. Future research should explore oxytocin and impulsivity-focused interventions to mitigate the effects of childhood trauma and reduce MUD development risk.

Walking against traffic and pedestrian injuries in the United Kingdom: new insights.

BACKGROUND: Studies from Finland and Taiwan have shown that walking against traffic was beneficial for reducing pedestrian crashes and fatalities. This study examined whether such beneficial effects are consistent across various circumstances. METHODS: This study aimed to investigate pedestrian fatalities in walking-against or with-traffic crashes by analysing the UK STATS19 crash data for the period between 1991 and 2020. We firstly employed Chi-square tests to examine risk factors for pedestrian injury severity. These variables were then incorporated into stepwise logistic regression models with multiple variables. We subsequently conducted joint effect analysis to investigate whether the beneficial effects of walking against traffic on injury severity vary across different situations. RESULTS: Our data contained 44,488 pedestrian crashes, of which 16,889 and 27,599 involved pedestrians walking against and with traffic, respectively. Pedestrians involved in with-traffic crashes were more likely to sustain fatalities (adjusted odds ratio [AOR] = 1.542; confidence interval [CI] = 1.139-1.927) compared with those in walking against-traffic crashes. The detrimental effect of walking with traffic on fatalities appeared to be more pronounced in darkness-unlit conditions (AOR = 1.48; CI = 1.29-1.70), during midnight hours (00:00-06:59 am) (AOR = 1.60; CI = 1.37-1.87), in rural areas (AOR = 2.20; CI = 1.92-2.51), when pedestrians were elderly (≥ 65 years old) (AOR = 2.65, CI = 2.16-3.26), and when heavy goods vehicles were crash partners (AOR = 1.51, CI = 1.28-1.78). CONCLUSIONS: Walking against traffic was beneficial in reducing pedestrian fatalities compared with walking with traffic. Furthermore, such a beneficial effect was more pronounced in darkness-unlit conditions, at midnights (00:00-06:59 am), in rural areas, when pedestrians were elderly, and when heavy goods vehicles struck pedestrians.

Handheld common-path swept-source optical coherence tomography angiography.

This study develops a handheld optical coherence tomography angiography (OCTA) system that uses a high-speed (200 kHz) swept laser with a dual-reference common-path configuration for stable and fast imaging. The common-path design automatically avoids polarization and dispersion mismatches by using one circulator as the primary system element, ensuring a cost-effective and compact design for handheld probe use. With its stable envelope (i.e., sub-µm shifts) and phase variation (corresponding to nm changes in axial displacement), the minimum detectable flow velocity is ∼ 0.08 mm/s in our experiment, which gives the common-path setup a high potential for application in a handheld OCTA system for clinical skin screening. In vivo skin structures and microvasculature networks on the dorsum of the hand and cheek of a healthy human are imaged successfully.

The Image-Histology Correlation of Subcutaneous mPEG-poly(Ala) Hydrogel-Embedded MIN6 Cell Grafts in Nude Mice.

Previously, we have successfully used noninvasive magnetic resonance (MR) and bioluminescence imaging to detect and monitor mPEG-poly(Ala) hydrogel-embedded MIN6 cells at the subcutaneous space for up to 64 days. In this study, we further explored the histological evolution of MIN6 cell grafts and correlated it with image findings. MIN6 cells were incubated overnight with chitosan-coated superparamagnetic iron oxide (CSPIO) and then 5 × 106 cells in the 100 µL hydrogel solution were injected subcutaneously into each nude mouse. Grafts were removed and examined the vascularization, cell growth and proliferation with anti-CD31, SMA, insulin and ki67 antibodies, respectively, at 8, 14, 21, 29 and 36 days after transplantation. All grafts were well-vascularized with prominent CD31 and SMA staining at all time points. Interestingly, insulin-positive cells and iron-positive cells were scattered in the graft at 8 and 14 days; while clusters of insulin-positive cells without iron-positive cells appeared in the grafts at 21 days and persisted thereafter, indicating neogrowth of MIN6 cells. Moreover, proliferating MIN6 cells with strong ki67 staining was observed in 21-, 29- and 36-day grafts. Our results indicate that the originally transplanted MIN6 cells proliferated from 21 days that presented distinctive bioluminescence and MR images.

Meta-Analysis of Electroencephalographic Correlates and Cognitive Performance for Acute Exercise-Induced Modulation.

INTRODUCTION: Although abundant research delving into the acute exercise-induced modulation of cognitive performance and the P300-ERP component has been conducted, there is a lack of consensus regarding whether or not this type of intervention has a beneficial effect on cognition and how it relates to the P300-ERP. METHODS: To examine the possible sources of this discrepancy, we conducted a meta-analysis of ERP results together with cognitive performance that were systemically stratified by relevant demographic and methodological moderators. RESULTS: Our results indicate that while acute exercise exerted an overall stable effect on cognitive improvement, associated with enlarged P300 amplitudes, the effect size varied across factors of age, biological sex, exercise intensity, exercise type, control type, and experimental design. Future research taking into consideration modulating factors as to avoid misestimating the beneficial effects of acute exercise are encouraged. CONCLUSION: All in all, and to our knowledge, this is the first meta-analysis quantitatively summarizing the relevant literature on the associations between P300-ERP correlates, acute exercise, and its positive influence on attention and cognitive performance in healthy individuals.

Noise-induced hearing loss profile among Taiwan Airforce on duty pilots.

PURPOSE: Noise-induced hearing loss (NIHL) often results in impaired functional hearing and accidental injuries; thus, reducing military performance and endangering flight safety. While a few studies addressing laterality (left-right ear differences) and NIHL incidence between fixed-winged (jet-fighter) and rotary-wing (helicopter) aircrafts yielded inconsistent results, little is known about the NIHL profile among different types of jet-fighter pilots. This study aims to conduct a fine-grained examination of NIHL among Airforce jet pilots, with planned comparisons of laterality and aircraft type, along with the goal to compare the sensitivity of different hearing indices in predicting military pilot NIHL. MATERIALS AND METHODS: This cross-sectional study utilizes the health and hearing data of 1025 Taiwanese Air Force Military pilots from the 2019 Taiwanese physical examination database to assess the changes in their hearing thresholds, and evaluate their risk for NIHL. RESULTS: Our results showed that, among available military aircraft types, the trainer aircraft and M2000-5 jet-fighter had the highest risk of NIHL, in addition to a left ear inferiority found in the overall population of military pilots. Among the three hearing indices used in this study -the International Organization for Standardization (ISO) three-point hearing index, the Occupational Safety and Health Administration (OSHA) three-point hearing index, and the American Academy of Otolaryngology-Head and Neck Surgery's (AAO-HNS) high-frequency three-point hearing index-, the OSHA the AAO-HNS were the most sensitive. CONCLUSION: Our results suggest a better noise protection for trainer and M2000-5 pilots, especially for the left ear, is warranted.

The neural correlates of emotional conflict monitoring as an early manifestation of affective and cognitive declines in persons with Type 2 diabetes.

Patients with Type 2 diabetes are known to be more susceptible to experience dementia and depression/anxiety. The neural circuits of emotional conflict monitoring, as indicated by a Stroop task, might become altered in terms of cognitive and affective impairments in diabetes. This study investigated alterations in the emotional conflict monitoring and associations of corresponding brain activities with metabolic parameters in persons with Type 2 diabetes. Participants with normal cognitive and affective functioning, including 40 persons with Type 2 diabetes and 30 non-diabetes control subjects, underwent a functional MRI paradigm with the face-word emotional Stroop task and detailed cognitive and affective assessments, including the Montreal Cognitive Assessment and Beck Anxiety Inventory. Compared with the controls, people with diabetes exhibited stronger emotional interference, as indicated by differential reaction times between congruent and incongruent trials (Δcon). Δcon was correlated with Montreal Cognitive Assessment test scores and fasting glucose levels. People with diabetes demonstrated altered brain activation and functional connectivity in the neural network for emotional conflict monitoring. The neural network for emotional conflict monitoring mediated the association of pancreatic function with anxiety scores as well as the relationship between Δcon and Montreal Cognitive Assessment scores. Results suggested that alterations in the neural network underlying emotional conflict monitoring might present before clinically measurable cognitive and affective decrements were apparent, thereby bridging the gap between dementia and anxiety/depression in persons with diabetes.

The anti-anxiety drug lorazepam changes implicit behaviors but not explicit evaluations of sense of agency under authoritative pressure: A functional magnetic resonance imaging study.

Previous research on coercion has neglected the fact that agents under authoritative pressure may also suffer from coercive power, which can trigger anxiety-like emotional negativity on its victims. Furthermore, high levels of neuroticism and/or anxiety have been found to be associated with the compliance of various forms of social pressure. In this study, we investigate the effects of the anxiolytic GABA A (gamma-Aminobutyric acid) modulator, lorazepam, on behavioral and neural responses to coercive power. Here, we applied a virtual obedience to authority paradigm alongside lorazepam administration (versus placebo), and during functional magnetic resonance imaging scanning. Our results show that lorazepam administration exerted differential effects on the reaction times (RTs) when initiating harming versus helping behaviors, with longer harming RTs compared to helping RTs, despite comparable subjective ratings regarding perceived coercion. Coercive harming significantly increased activity in the amygdala, hippocampus, orbitofrontal cortex, and dorsolateral prefrontal cortex (dlPFC). Lorazepam administration decreased amygdala and hippocampus activity, but increased dlPFC and right temporoparietal junction activations. The lower activity in the hippocampus predicted higher ratings for perceived coercion. Furthermore, lorazepam significantly decreased the functional connectivity of the hippocampus with the dlPFC during coercive harming. In conclusion, we provide evidence -by incorporating multimodal indices, including neuroimaging, neuropharmacological interventions, and behavioral assessments- to posit that the GABA A agonist, lorazepam, might aid as a possible intervention in service of coping strategies against coercion.

Neuromodulation of the right temporoparietal junction alters amygdala functional connectivity to authority pressure.

Past historical events and experimental research have shown that complying with orders from an authority has a strong impact on harming/destructive behavior, but no one has ever looked into the potential intervention and its neural underpinning to reveal the toll of coercion. We used a paradigm of virtual obedience to authority, in which an experimenter ordered a volunteer to press a handheld button to initiate actions that carried different consequences, including harming or helping others. In this study, we scanned the brain with functional neuroimaging and applied transcranial direct current stimulation (tDCS) to modulate the activation of the right temporoparietal junction (rTPJ) in healthy volunteers in a single-blinded, sham-controlled, crossover trial with anodal, cathodal, and sham stimulation. We observed that cathodal stimulation, compared to anodal and sham stimulation, significantly reduced reaction times (RTs) to initiating harming actions. The effect of tDCS on the rTPJ, orbitofrontal cortex, and anterior cingulate cortex had opposite directions depending on coercive harming or helping actions. Cathodal tDCS-induced changes in the strength of the functional connectivity between the rTPJ and amygdala predicted the effect of cathodal tDCS on harming RTs. The findings provide evidence supporting the rTPJ having a role in coercion-induced changes in the sense of agency. Neuromodulation with tDCS might help in unveiling the power of authority and assisting in the emergence of prosocial behavior, thus shedding light on coping strategies against coercion beyond merely examining its effects.

Meta-analysis of functional neuroimaging and dispositional variables for clinical empathy.

Clinical empathy refers to the ability of healthcare providers (HP) to recognize and understand what patients feel. While neuroimaging investigations have identified a neural network of empathy, activation consistency of brain regions and their specific functions in clinical empathy remains unclear. Herein, we conducted meta-analyses of dispositional assessments using random-effects models and functional neuroimaging using Seed-based d Mapping with Permutation of Subject Images to ascertain the shared neural processes consistently identified as relevant to clinical empathy. The dispositional meta-analysis (n = 15) revealed that HP exhibited higher scores on empathic concern and perspective taking. The HP neuroimaging meta-analysis (n = 11) identified consistent activation of the anterior mid-cingulate cortex, anterior insula, and ventrolateral prefrontal cortex (vlPFC) while HP vs. controls comparison (n = 9) did not yield robust alterations. The vlPFC mediated positive and negative functional connectivity of the insula. We revisited the framework of emotion regulation in clinical empathy. The empathetic agent flexibly shifts between affective regulatory strategies to meet contextual demands, with vlPFC figuring as the key region where this neural mechanism takes place.

The neural mediators of moral attitudes and behaviors.

Morality is central for humanity. It has been suggested that our memories of past events involving moral actions contribute to shaping a positive view of the self. Nevertheless, it remains unclear how individual variability in moral attitudes fosters/affects moral behaviors. Here, we used a button-trigger task, where participants mentally simulated themselves as the agents of moral and immoral behaviors (study 1: N = 96). Helping actions appeared to have significantly faster reaction times (RTs) than neutral and harming actions. We also measured the fMRI activity while undergoing such moral actions in another sample (study 2: N = 117). Individual variability among implicit social attitudes (sIAT) predicted quicker RTs for helping actions, and explicit justice sensitivity (JSI) predicted higher warm-glow ratings for helping. Furthermore, the orbitofrontal cortex mediated sIAT-RTs association, while the right temporoparietal junction mediated the JSI-warm-glow linkage. These findings support the dynamic system framework of moral cognition, providing key knowledge on the neural underpinnings regarding individual variability on moral attitudes.

Magnetic Resonance Imaging of Transplanted Porcine Neonatal Pancreatic Cell Clusters Labeled with Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles.

Recently, we have shown that manganese magnetism-engineered iron oxide nanoparticles (MnMEIO NPs) conjugated with exendin-4 (Ex4) act as a contrast agent that directly trace implanted mouse islet ß-cells by magnetic resonance imaging (MRI). Here we further advanced this technology to track implanted porcine neonatal pancreatic cell clusters (NPCCs) containing ducts, endocrine, and exocrine cells. NPCCs from one-day-old neonatal pigs were isolated, cultured for three days, and then incubated overnight with MnMEIO-Ex4 NPs. Binding of NPCCs and MnMEIO-Ex4 NPs was confirmed with Prussian blue staining in vitro prior to the transplantation of 2000 MnMEIO-Ex4 NP-labeled NPCCs beneath the left renal capsule of six nondiabetic nude mice. The 7.0 T MRI on recipients revealed persistent hypointense areas at implantation sites for up to 54 days. The MR signal intensity of the graft on left kidney reduced 62-88% compared to the mirror areas on the contralateral kidney. Histological studies showed colocalization of insulin/iron and SOX9/iron staining in NPCC grafts, indicating that MnMEIO-Ex4 NPs were taken up by mature ß-cells and pancreatic progenitors. We conclude that MnMEIO-Ex4 NPs are excellent contrast agents for detecting and long-term monitoring implanted NPCCs by MRI.

Interaction effects of the 5-HTT and MAOA-uVNTR gene variants on pre-attentive EEG activity in response to threatening voices.

Both the serotonin transporter polymorphism (5-HTTLPR) and the monoamine oxidase A gene (MAOA-uVNTR) are considered genetic contributors for anxiety-related symptomatology and aggressive behavior. Nevertheless, an interaction between these genes and the pre-attentive processing of threatening voices -a biological marker for anxiety-related conditions- has not been assessed yet. Among the entire sample of participants in the study with valid genotyping and electroencephalographic (EEG) data (N = 140), here we show that men with low-activity MAOA-uVNTR, and who were not homozygous for the 5-HTTLPR short allele (s) (n = 11), had significantly larger fearful MMN amplitudes -as driven by significant larger ERPs to fearful stimuli- than men with high-activity MAOA-uVNTR variants (n = 20). This is in contrast with previous studies, where significantly reduced fearful MMN amplitudes, driven by increased ERPs to neutral stimuli, were observed in those homozygous for the 5-HTT s-allele. In conclusion, using genetic, neurophysiological, and behavioral measurements, this study illustrates how the intricate interaction between the 5-HTT and the MAOA-uVNTR variants have an impact on threat processing, and social cognition, in male individuals (n = 62).

Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted ß-Cells.

To specifically detect and trace transplanted islet ß-cells by magnetic resonance imaging (MRI), we conjugated manganese magnetism-engineered iron oxide nanoparticles (MnMEIO NPs) with exendin-4 (Ex4) which specifically binds glucagon-like peptide-1 receptors on the surface of ß-cells. The size distribution of MnMEIO and MnMEIO-Ex4 NPs were 67.8 ± 1.3 and 70.2 ± 2.3 nm and zeta potential 33.3 ± 0.5 and 0.6 ± 0.1 mV, respectively. MnMEIO and MnMEIO-Ex4 NPs with iron content ≤ 40 µg/mL did not affect MIN6 ß-cell viability and insulin secretion. Positive iron staining was found in MIN6 ß-cells loaded with MnMEIO-Ex4 NPs but not in those with MnMEIO NPs. A transmission electron microscope confirmed MnMEIO-Ex4 NPs were distributed in the cytoplasm of MIN6. In vitro MR images revealed a loss of signal intensity in MIN6 ß-cells labeled with MnMEIO-Ex4 NPs but not with MnMEIO NPs. After transplantation of islets labeled with MnMEIO-Ex4, the graft under kidney capsule could be visualized on MRI as persistent hypointense areas up to 17 weeks. Moreover, histology of the islet graft showed positive staining for insulin, glucagon and iron. Our results indicate MnMEIO-Ex4 NPs are safe and effective for the detection and long-term monitoring of transplanted ß-cells by MRI.