Modulation of Neural Activity in the Temporoparietal Junction with Transcranial Direct Current Stimulation Changes the Role of Beliefs in Moral Judgment

Judgments about whether an action is morally right or wrong typically depend on our capacity to infer the actor’s beliefs and the outcomes of the action. Prior neuroimaging studies have found that mental state (e.g., beliefs, intentions) attribution for moral judgment involves a complex neural network that includes the temporoparietal junction (TPJ). However, neuroimaging studies cannot demonstrate a direct causal relationship between the activity of this brain region and mental state attribution for moral judgment. In the current study, we used transcranial direct current stimulation (tDCS) to transiently alter neural activity in the TPJ. The participants were randomly assigned to one of three stimulation treatments (right anodal/left cathodal tDCS, left anodal/right cathodal tDCS, or sham stimulation). Each participant was required to complete two similar tasks of moral judgment before receiving tDCS and after receiving tDCS. We studied whether tDCS to the TPJ altered mental state attribution for moral judgment. The results indicated that restraining the activity of the right temporoparietal junction (RTPJ) or the left the temporoparietal junction (LTPJ) decreased the role of beliefs in moral judgments and led to an increase in the dependence of the participants’ moral judgments on the action’s consequences. We also found that the participants exhibited reduced reaction times both in the cases of intentional harms and attempted harms after receiving right cathodal/left anodal tDCS to the TPJ. These findings inform and extend the current neural models of moral judgment and moral development in typically developing people and in individuals with neurodevelopmental disorders such as autism

Photometry of the Didymos System across the DART Impact Apparition

On 2022 September 26, the Double Asteroid Redirection Test (DART) spacecraft impacted Dimorphos, the satellite of binary near-Earth asteroid (65803) Didymos. This demonstrated the efficacy of a kinetic impactor for planetary defense by changing the orbital period of Dimorphos by 33 minutes. Measuring the period change relied heavily on a coordinated campaign of lightcurve photometry designed to detect mutual events (occultations and eclipses) as a direct probe of the satellite’s orbital period. A total of 28 telescopes contributed 224 individual lightcurves during the impact apparition from 2022 July to 2023 February. We focus here on decomposable lightcurves, i.e., those from which mutual events could be extracted. We describe our process of lightcurve decomposition and use that to release the full data set for future analysis. We leverage these data to place constraints on the postimpact evolution of ejecta. The measured depths of mutual events relative to models showed that the ejecta became optically thin within the first ∼1 day after impact and then faded with a decay time of about 25 days. The bulk magnitude of the system showed that ejecta no longer contributed measurable brightness enhancement after about 20 days postimpact. This bulk photometric behavior was not well represented by an HG photometric model. An HG 1 G 2 model did fit the data well across a wide range of phase angles. Lastly, we note the presence of an ejecta tail through at least 2023 March. Its persistence implied ongoing escape of ejecta from the system many months after DART impact

Cloning, functional characterization and catalytic mechanism of a bergaptol O-methyltransferase from Peucedanum praeruptorum Dunn

Coumarins are main active components of Peucedanum praeruptorum Dunn. Among them, methoxylated coumarin compound, such as bergapten, xanthotoxin and isopimpinellin, has high officinal value and plays an important role in medicinal field. However, major issues associated with the biosynthesis mechanism of coumarins remain unsolved and no corresponding enzyme has been cloned from P. praeruptorum. In this study, a local BLASTN program was conducted to find the candidate genes from P. praeruptorum transcriptome database using the nucleotide sequence of Ammi majus bergaptol O-methyltransferase (AmBMT, GenBank accession No: AY443006) as a template. As a result, a 1335 bp full-length of cDNA sequence which contains an open reading frame of 1080 bp encoding a BMT polypeptide of 359 amino acids was obtained. The recombinant protein was functionally expressed in Escherichia coli and displayed an observed activity to bergaptol. In vitro experiments show that the protein has narrow substrate specificity for bergaptol. Expression profile indicated that the cloned gene had a higher expression level in roots and can be induced by methyl jasmonate (MeJA). Subcellular localization analysis showed that the BMT protein was located in cytoplasm in planta. Homology modeling and docking based site-directed mutagenesis have been employed to investigate the amino acid residues in BMT required for substrate binding and catalysis. Conservative amino acid substitutions at residue H264 affected BMT catalysis, whereas substitutions at residues F171, M175, D226 and L312 affected substrate binding. The systemic study summarized here will enlarge our knowledge on OMTs and provide useful information in investigating the coumarins biosynthesis mechanism in P. praeruptorum

MicroRNAs 99b-5p/100-5p regulated by endoplasmic reticulum stress are involved in Abeta-induced pathologies

Alzheimer’s disease (AD) is the most common cause of dementia. Amyloid beta (Abeta) deposition and intracellular tangles are the pathological hallmarks of AD. MicroRNAs (miRNAs) are small non-coding RNAs which have been found to play very important roles and have the potential to serve as diagnostic markers during neuronal pathogenesis. In this study, we aimed to determine the roles of miR-99b-5p and miR-100-5p in Abeta-induced neuronal pathologies. We detected the expression levels of miR-99b-5p and miR-100-5p in the brains of APPswe/PS1ΔE9 double transgenic mice (APP/PS1 mice) at different age stages and found both miRNAs were decreased at early stages while increased at late stages of APP/PS1 mice when compared with the age-matched wild type (WT) mice. Similar phenomenon was also observed in Abeta-treated cultured cells. We also confirmed that mTOR (mammalian target of rapamycin) is one of the targets of miR-99b-5p/100-5p, which is consistent with previous studies in cancer. MiR-99b-5p/100-5p have been found to promote cell apoptosis with the Abeta treatment. This effect may be induced via the mTOR pathway. In our study, we find both miR-99b-5p and miR-100-5p affect neuron survival by targeting mTOR. We also speculate that dynamic change of miR-99b-5p/100-5p levels during Abeta-associated pathologies might be attributed to Abeta-induced endoplasmic reticulum stress (ER stress), suggesting the potential role of the ER stress –miRNAs – mTOR axis in Abeta-related AD pathogenesis

Integration of a decrescent transcriptome and metabolomics dataset of Peucedanum praeruptorum to investigate the CYP450 and MDR genes involved in coumarins biosynthesis and transport

Abstract Peucedanum praeruptorum Dunn is well-known traditional Chinese medicine. However, little is known in the biosynthesis and the transport mechanisms of its coumarin compounds at the molecular level. Although transcriptomic sequence is playing an increasingly significant role in gene discovery, it is not sufficient in predicting the specific function of target gene. Furthermore, there is also a huge database to be analyzed. In this study, RNA sequencing assisted transcriptome dataset and high-performance liquid chromatography (HPLC) coupled with electrospray-ionization quadrupole time-of-flight mass spectrometry (Q-TOF MS)-based metabolomics dataset of P. praeruptorum were firstly constructed for gene discovery and compound identification. Subsequently, methyl jasmonate (MeJA)-induced gene expression analysis and metabolomics analysis were conducted to narrow-down the dataset for selecting the candidate genes and the potential marker metabolites. Finally, the genes involved in coumarins biosynthesis and transport were predicted with parallel analysis of transcript and metabolic profiles. As a result, a total of 40952 unigenes and 19 coumarin compounds were obtained. Based on the results of gene expression and metabolomics analysis, 7 cytochrome-P450 and 8 multidrug resistance transporter unigenes were selected as candidate genes and 8 marker compounds were selected as biomarkers, respectively. The parallel analysis of gene expression and metabolites accumulation indicated that the gene labeled as 23746, 228 and 30922 were related to the formation of the coumarin core compounds whereas 36276 and 9533 participated in the prenylation, hydroxylation, cyclization or structural modification. Similarly, 1462, 20815 and 15318 participated in the transport of coumarin core compounds while 124029 and 324293 participated in the transport of the modified compounds. This finding suggested that integration of a decrescent transcriptome and metabolomics dataset could largely narrow down the number of gene to be investigated and significantly improve the efficiency of functional gene predication. In addition, the large amount of transcriptomic data produced from P. praeruptorum and the genes discovered in this study would provide useful information in investigating the biosynthesis and transport mechanism of coumarins

Frequency-Specific Alternations in the Amplitude of Low-Frequency Fluctuations in Chronic Tinnitus

Tinnitus, a phantom ringing, buzzing or hissing sensation with potentially debilitating consequences, is thought to arise from aberrant spontaneous neural activity at one or more sites within the central nervous system; however, the location and specific features of these oscillations are poorly understood with respect to specific tinnitus features. Recent resting-state functional magnetic resonance imaging (fMRI) studies suggest that aberrant fluctuations in spontaneous low-frequency oscillations (LFO) of the blood oxygen level-dependent (BOLD) signal may be an important factor in chronic tinnitus; however, the role that frequency-specific components of LFO play in subjective tinnitus remains unclear. A total of 39 chronic tinnitus patients and 41 well-matched healthy controls participated in the resting-state fMRI scans. The LFO amplitudes were investigated using the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) in two different frequency bands (slow-4: 0.027-0.073 Hz and slow-5: 0.01-0.027 Hz). We observed significant differences between tinnitus patients and normal controls in ALFF/fALFF in the two bands (slow-4 and slow-5) in several brain regions including the superior frontal gyrus (SFG), inferior frontal gyrus, middle temporal gyrus, angular gyrus, supramarginal gyrus, and middle occipital gyrus. Across the entire subject pool, significant differences in ALFF/fALFF between the two bands were found in the midbrain, basal ganglia, hippocampus and cerebellum (Slow 4>Slow 5), and in the middle frontal gyrus, supramarginal gyrus, posterior cingulate cortex, and precuneus (Slow 5>Slow 4). We also observed significant interaction between frequency bands and patient groups in the orbitofrontal gyrus. Furthermore, tinnitus distress was positively correlated with the magnitude of ALFF in right SFG and the magnitude of fALFF slow-4 band in left SFG, whereas tinnitus duration was positively correlated with the magnitude of ALFF in right SFG and the magnitude of fALFF slow-5 band in left SFG. Resting-state fMRI provides an unbiased method for identifying aberrant spontaneous LFO occurring throughout the central nervous system. Chronic tinnitus patients have widespread abnormalities in ALFF and fALFF slow-4 and slow-5 band which are correlated with tinnitus distress and duration. These results provide new insights on the neuropathophysiology of chronic tinnitus; therapies capable of reversing these aberrant patterns may reduce tinnitus distress