Biology subjects

Zeng, Y.

Publications and source records attributed to Zeng, Y..

At least 145 records · Page 8Linked to original sources

bioRxiv2022

Epidermal threads reveal the origin of hagfish slime

Fiber-reinforced soft materials possess high flexibility with high strength but are rare in nature. Hagfishes can produce a tough, fibrous slime within a fraction of a second by ejecting two cellular products, mucus and threads, into seawater. With thousands of silk-like threads, the slime is highly effective in defending against large predators. However, the evolutionary origin of hagfish slime remains unresolved, with the presence of another, putatively homologous thread in the epidermis providing circumstantial evidence for an epidermal origin. Here, we investigated the epidermal threads produced in hagfish skin. We found that these threads average [~]2 mm in length and [~]0.5 m in diameter, or [~]80 times shorter and [~]4 times thinner than the slime threads, characterizing the second longest intracellular fiber. The entire hagfish body is covered by a dense layer of epidermal thread cells, with each square millimeter of skin storing a total of [~]96 cm threads. Experimentally induced damage to a hagfishs skin caused the release of threads, which together with mucus, formed an adhesive epidermal slime that is more fibrous and less dilute than the defensive slime. Transcriptome analyses further revealed that the epidermal threads are ancestral to the slime threads, with duplication and diversification of thread genes in parallel with the evolution of slime glands. These results support an epidermal origin of hagfish slime and slime glands, as driven by predator selection for stronger and more voluminous slime.

evolutionary biology↗

bioRxiv2022

Aspartate reduces liver inflammation and fibrosis by suppressing the NLRP3 inflammasome pathway via upregulating NS3TP1 expression

Aspartate (Asp) can act on liver Kupffer cells, inhibit NOD-like receptor-P 3 (NLRP3) inflammatory bodies, and improve liver inflammation in acute hepatitis. However, the effect of Asp on the role of hepatic stellate cells (HSCs) in the pathogenesis of liver fibrosis in chronic liver injury remains unexplored. This study aimed to investigate the effects of Asp on CCl4-induced liver fibrosis in mice and HSCs via the NF-{kappa}B/ NLRP3 signaling pathway. Liver fibrosis was induced in C57BL/6J mice by intraperitoneally (IP) injecting 0.5 mL/kg 2% CCl4 three times weekly for 8 weeks. Asp was administered to mice by gavage once every morning for 4 weeks. Massons trichrome staining, Sirius red staining and hematoxylin and eosin staining were used to detect and analyze the pathological changes in liver tissues. Western blot analysis and immunohistochemistry were applied to determine the protein expression levels of -smooth muscle actin (-SMA), collagen III (COL III), NLRP3, and IL-1{beta}. Also, reverse transcription-quantitative PCR was performed to detect the mRNA expression levels. In the liver fibrosis model, the pathological changes in liver tissues improved following treatment with Asp. A marked decrease was observed in protein and mRNA expression levels of -SMA, COL III, NLRP3, and IL-1{beta}. In addition, HSCs were treated with Asp. The expression levels of -SMA, COL III, NLRP3, and IL-1{beta} reduced in dose- and time-dependent manners. Furthermore, Asp upregulated the expression of NS3TP1 in vivo and in vitro, and NS3TP1 had a significant inhibitory effect on liver fibrosis. Asp attenuated liver fibrosis and reduced collagen production by suppressing the NF-{kappa}B/ NLRP3 signaling pathway via upregulating the expression of NS3TP1.

molecular biology↗

bioRxiv2022

Cell wall extensin arabinosylation is required for root directional response to salinity

Soil salinity is a major contributor to crop yield losses. To improve our understanding of root responses to salinity, we developed and exploit here a real-time salt-induced tilting assay (SITA). This method follows root growth upon both gravitropic and salt challenges, revealing that root bending upon tilting is modulated by salinity, but not by osmotic stress. Next, this salt-specific response was measured in 345 natural Arabidopsis accessions and we discovered a genetic locus, encoding for the cell-wall modifying enzyme EXTENSIN ARABINOSE DEFICIENT TRANSFERASE (ExAD), to be associated with root bending in salt. Extensins are a class of structural cell wall glycoproteins [hydroxyproline-rich glycoproteins (HRGPs)] which are post-translationally modified by O-glycosylation mostly in the form of hydroxyproline (Hyp)-arabinosylation. We show that salt induces ExAD-dependent Hyp-arabinosylation, influencing root bending responses and cell wall thickness. We report that roots of exad mutants, which lack extensin Hyp-Araf4 modifications, display increased root epidermal cell wall thickness and porosity and altered gravitropic root bending in salt, as well as a reduced salt avoidance response. Our results suggest that extensin modification via Hyp-arabinosylation represents a novel salt-specific cellular process that is required for the directional response of roots exposed to salinity.

plant biology↗

bioRxiv2022

A gut commensal protist protects against virus-mediated loss of oral tolerance

Loss of oral tolerance (LOT) to gluten, characterized by a T helper 1 (Th1) gluten-specific immune response, is a hallmark of celiac disease (CeD) and can be triggered by enteric viral infections. We hypothesized that certain gut microbes have the capacity to protect against virus-mediated LOT. By using our previously defined reovirus-mediated LOT CeD model, we discovered that the gut colonizing protist Tritrichomonas (T.) arnold promotes oral tolerance and protects against reovirus-mediated LOT by suppressing the reovirus-induced proinflammatory program of dietary-antigen-presenting CD103+ dendritic cells. Importantly, T. arnold did not affect antiviral host immunity, suggesting that T. arnold-mediated protection against T1L-induced LOT is not attributable to differences in antiviral host responses. Additionally, using gnotobiotic mice, we found that Tritrichomonas arnold colonization is sufficient to protect against reovirus-mediated LOT in the absence of the microbiota. Mechanistically, we show that Tritrichomonas arnold colonization restrains reovirus-induced inflammatory responses in dendritic cells and thus limit their ability to promote Th1 immune responses ex vivo. Finally, our studies using human stool samples support a role for Tritrichomonas sp. colonization in protecting against development of CeD. This study will motivate the design of effective therapies to prevent LOT to gluten in at-risk individuals and to reinstate tolerance to gluten in CeD patients. One Sentence SummaryTritrichomonas arnold protects against virus-mediated loss of oral tolerance to gluten and is underrepresented in celiac disease patients.

immunology↗

bioRxiv2022

Pharmaco-Pheno-Multiomic Integration Reveals Biomarker Profiles and Therapeutic Response Prediction Models in Leukemia and Ovarian Cancer

Despite considerable progress made in improving therapeutic strategies, the overall survival for patients diagnosed with various cancer types remains low. Further, patients often cycle through multiple therapeutic options before finding an effective regimen for the specific malignancy being treated. A focus on building enhanced computational models, which prioritize therapeutic regimens based on a tumors complete molecular profile, will improve the patient experience and augment initial outcomes. In this study, we present an integrative analysis of multiple omic datasets coupled with phenotypic and therapeutic response profiles of Cytarabine from a cohort of primary AML tumors, and Olaparib from a cohort of Patient-Derived Xenograft (PDX) models of ovarian cancer. These analyses, termed Pharmaco-Pheno-Multiomic (PPMO) Integration, established novel complex biomarker profiles that were used to accurately predict prospective therapeutic response profiles in cohorts of newly profiled AML and ovarian tumors. Results from the computational analyses also provide new insights into disease etiology and the mechanisms of therapeutic resistance. Collectively, this study provides proof-of-concept in the use of PPMO to establish highly accurate predictive models of therapeutic response, and the power of leveraging this method to unveil cancer disease mechanisms.

cancer biology↗

bioRxiv2022

Endothelial TET2 Regulates Cardiac Remodeling by Modifying Endothelial-to-Mesenchymal Transition

DNA methylation modification has been proved to play an important role in heart diseases. In this study, the role of Ten-Eleven Translocation-2 (TET2), which is a key demethylation enzyme, is investigated in cardiac remodeling. TET2 is abundant in endothelial cells but decreased in hypertrophic hearts. TET2 knockdown in endothelial cells triggers endothelial-to-mesenchymal transition (EndMT), while overexpression of TET2 inhibits the EndMT. In vivo, Cdh5-CreERT2/TET2flox/flox; Rosa26-mTmG+/- mice are developed and undergo transverse aortic constriction (TAC) subsequently to induce pathological cardiac hypertrophy model. Hearts of Cdh5-CreERT2/TET2flox/flox mice show more severe hypertrophy and fibrosis than controls in the TAC model. Furthermore, EGLN3 is identified to participate in EndMT as the downstream target of TET2 by using RNA sequencing and whole-genome bisulfite sequencing (WGBS). Finally, vitamin C, which can mimic TET2 restoration, is found to partially improve cardiac function and inhibit myocardial fibrosis. These insights into how TET2 alleviates cardiac fibrosis may open new avenues for treating cardiac remodeling in the future.

genetics↗

bioRxiv2022

Beyond winglets: evolution of flight-related morphology in stick insects (Phasmatodea)

The first winged insects evolved from a wingless ancestor, but details of the transition to a fully-winged morphology remain unclear. Studying extant pterygotes with partial wings, such as the stick insects (Order Phasmatodea), may help us to understand such a transition. Here, we address how a series of flight-related morphological parameters may correlate with flight evolution by studying different phasmids representing a volancy continuum ranging from miniaturized to full-sized wings. Variation in phasmid wing shape, venation, wing mass and the mass of flight muscle can be described by specific scaling laws referenced to wing length and wing loading. Also, the mass distribution of the body-leg system is conserved in spite of a wide range of variation in body shape. With reduced wing size and increased wing loading, the longitudinal position of the wing-bearing thoracic segments is shifted closer to the insects center of body mass. These results demonstrate complex reconfiguration of the flight system during wing morphological transitions in phasmids, with various anatomical features potentially correlated with reduced flight performance attained with partial wings. Although these data represent phasmid-specific features of the flight apparatus and body plan, the associated scaling relationships can provide insight into functionality of intermediate conditions between wingless and fully-winged insects more generally.

evolutionary biology↗

bioRxiv2022

One-Pot Endonucleolytically Exponentiated Rolling Circle Amplification by CRISPR-Cas12a Affords Sensitive, Expedited Isothermal Detection of MicroRNAs

MicroRNAs (miRNAs) are a class of short non-coding RNAs that play essential roles in gene expression regulation. While miRNAs offer a promising source for developing potent cancer biomarkers, the progress towards clinical utilities remains largely limited, due in part to the long-standing challenge in sensitive, specific, and robust detection of miRNAs in human biofluids. Emerging next-generation molecular technologies, such as the CRISPR-based methods, promise to transform nucleic acid testing. The prevailing strategy used in existing CRISPR-based methods is to hyphenate two separate reactions for pre-amplification, e.g., rolling circle amplification (RCA), and amplicon detection by Cas12a/13a trans-cleavage in tandem. Thus, existing CRISPR-based miRNA assays require multiple manual steps and lack the analytical performance of the gold standard, RT-qPCR. Radically deviating from the existing strategies, we developed a one-step, one-pot isothermal miRNA assay termed "Endonucleolytically eXponenTiated Rolling circle Amplification with the dual-functional CRISPR-Cas12a" (EXTRA-CRISPR) to afford RT-PCR-like performance for miRNA detection. We demonstrated the superior analytical performance of our EXTRA-CRISPR assay to detect miRNAs (miR-21, miR-196a, miR-451a, and miR-1246) in plasma extracellular vesicles, which allowed us to define a potent EV miRNA signature for detection of pancreatic cancer. The analytical and diagnostic performance of our one-pot assay were shown to be comparable with that of the commercial RT-qPCR assays, while greatly simplifying and expediting the analysis workflow. Therefore, we envision that our technology provides a promising tool to advance miRNA analysis and clinical marker development for liquid biopsy-based cancer diagnosis and prognosis.

bioengineering↗

bioRxiv2022

Guiding Irregular Nuclear Morphology on Nanopillar Array for Malignancy Differentiation in Tumor cells

For more than a century, abnormal nuclei in tumor cells, presenting subnuclear invaginations and folds on the nuclear envelope, have been known to be associated with high malignancy and poor prognosis. However, current nuclear morphology analysis focuses on the features of the entire nucleus, overlooking the malignancy-related subnuclear features in nanometer scale. The main technical challenge is to probe such tiny and randomly distributed features inside cells. We here employ nanopillar arrays to guide subnuclear features into ordered patterns enabling their quantification as a strong indicator of cell malignancy. Both breast and liver cancer cells were validated, as well as the quantification of nuclear abnormality heterogeneity. The alterations of subnuclear patterns were also explored as effective readouts for drug treatment. We envision this nanopillar-enabled quantification of subnuclear abnormal features in tumor cells opens a new angle in characterizing malignant cells and studying the unique nuclear biology in cancer. TeaserA nanopillar-based assay quantifying the abnormal nuclear morphology in tumor cells at single-cell level.

bioengineering↗

bioRxiv2022

DiSCs: Domains involving SETDB1 and Cohesin are critical regulators of genome topology and stem cell fate

SETDB1 is a key regulator of lineage-specific genes and endogenous retroviral elements (ERVs) through its deposition of repressive H3K9me3 mark. Apart from its H3K9me3 regulatory role, SETDB1 has seldom been studied in terms of its other potential regulatory roles. To investigate this, a genomic survey of SETDB1 binding in mouse embryonic stem cells across multiple libraries was conducted, leading to the unexpected discovery of regions bereft of common repressive histone marks (H3K9me3, H3K27me3). These regions were enriched with the CTCF motif that is often associated with the topological regulator Cohesin. Further profiling of these non-H3K9me3 regions led to the discovery of a cluster of non-repeat loci that were co-bound by SETDB1 and Cohesin. These regions, which we named DiSCs (Domains involving SETDB1 and Cohesin) were seen to be proximal to the gene promoters involved in embryonic stem cell pluripotency and lineage development. Importantly, it was found that SETDB1-Cohesin co-regulate target gene expression and genome topology at these DiSCs. Depletion of SETDB1 led to localized dysregulation of Cohesin binding thereby locally disrupting topological structures. Dysregulated gene expression trends revealed the importance of this cluster in ES cell maintenance as well as at gene islands that drive differentiation to other lineages. The unearthing of the DiSCs thus unravels a unique topological and transcriptional axis of control regulated chiefly by SETDB1.

genomics↗

bioRxiv2022

Genetic control of KRAB-ZFP genes explains distal CpG-site methylation which associates with human disease phenotypes.

Kruppel-associated box zinc finger proteins (KRAB-ZFPs) are the largest gene family of transcriptional regulators in higher vertebrates. We have developed a method for inferring these factors DNA binding-sites in vivo. We achieved this by combining the genome-wide association of methylation at 573,027 CpG-sites (meQTL) in blood and KRAB-ZFP RNA expression changes (eQTL). This methods efficacy is clearly demonstrated by showing that the CpG-sites whose methylation is affected by KRAB-ZFP expression changes occur preferentially near KRAB-ZFP binding-sites in the HEK293T cell line. We found such an enrichment to be significant for 31% of factors tested. In addition, we found that binding-sites of many KRAB-ZFPs are significantly enriched (or sometimes depleted) in disease-associated CpG-sites. In total, 9% (11 of 125) of the traits tested, and 14% (32 of 222) of the factors (KRAB-ZFPs and TIF1-beta) tested, were enriched or depleted in one or more trait-factor pairing. Rheumatoid arthritis and human immunodeficiency virus (HIV) infection were associated with the largest number of KRAB-ZFP enrichments. There have been variable reports on the effects on HIV infection dynamics of transcription intermediary factor 1-beta (TIF1-beta, also known as KAP1 or TRIM28), a nuclear corepressor for KRAB-ZFPs. We provide evidence that KRAB-ZFP-independent effects of TIF1-beta are responsible for the decreased methylation of CpG-sites within its binding-sites that is observed in HIV infection. In conclusion, KRAB-ZFPs often affect CpG-site methylation within the proximity of their binding-sites, and CpG-sites within the binding-sites of KRAB-ZFPs are enriched for association with many traits, including rheumatoid arthritis and HIV infection.

genomics↗

bioRxiv2021

seGMM: a new tool to infer sex from massively parallel sequencing data

Inspecting concordance between self-reported sex and genotype-inferred sex from genomic data is a significant quality control measure in clinical genetic testing. Numerous tools have been developed to infer sex for genotyping array, whole-exome sequencing, and whole-genome sequencing data. However, improvements in sex inference from targeted gene sequencing panels are warranted. Here, we propose a new tool, seGMM, which applies unsupervised clustering (Gaussian Mixture Model) to determine the gender of a sample from the called genotype data integrated aligned reads. seGMM consistently demonstrated > 99% sex inference accuracy in publicly available (1000 Genomes) and our in-house panel dataset, which achieved obviously better sex classification than existing popular tools. Compared to including features only in the X chromosome, our results show that adding additional features from Y chromosomes (e.g. reads mapped to the Y chromosome) can increase sex classification accuracy. Notably, for WES and WGS data, seGMM also has an extremely high degree of accuracy. Finally, we proved the ability of seGMM to infer sex in single patient or trio samples by combining with reference data and pinpointing potential sex chromosome abnormality samples. In general, seGMM provides a reproducible framework to infer sex from massively parallel sequencing data and has great promise in clinical genetics.

bioinformatics↗

bioRxiv2021

Efficient inhibition of cell proliferation and promotion of apoptosis requires continuous treatment with abemaciclib.

Abemaciclib is an oral, selective cyclin-dependent kinase 4 & 6 inhibitor (CDK4 & 6i), approved for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) as monotherapy for endocrine refractory disease, and with endocrine therapy (ET) for initial treatment and after progression on ET. Abemaciclib has also shown clinical activity in combination with ET in patients with high risk early BC (EBC). Here, we examined the preclinical attributes of abemaciclib and other CDK4 & 6i using biochemical and cell-based assays. In vitro, abemaciclib preferentially inhibited CDK4 kinase activity versus CDK6, resulting in inhibition of cell proliferation in a panel of BC cell lines with higher average potency than palbociclib or ribociclib. Abemaciclib showed activity regardless of HER2 amplification and phosphatidylinositol 3-kinase (PI3KCA) gene mutation status. In human bone marrow progenitor cells, abemaciclib showed lower impact on myeloid maturation than other CDK4 & 6i when tested at unbound concentrations similar to those observed in clinical trials. Continuous abemaciclib treatment provided profound inhibition of cell proliferation, and triggered senescence and apoptosis. These preclinical results support the unique efficacy and safety profile of abemaciclib observed in clinical trials.

cell biology↗

bioRxiv2021

Upregulated PD-1 Signaling is an Important Antagonist to Glomerular Health in Aged Kidneys

Kidney aging and its contribution to disease and its underlying mechanisms are not well understood. With an aging population, kidney health becomes an important medical and socioeconomic factor. We previously showed that podocytes isolated from aged mice exhibit increased expression of Programed Cell Death Protein 1 (PD-1) surface receptor and its two ligands (PD-L1, PD-L2). PDCD1 transcript increases with age in micro-dissected human glomeruli, which correlates with lower eGFR, and higher segmental glomerulosclerosis and vascular arterial intima to lumen ratio. In vitro studies in podocytes demonstrate a critical role for PD-1 signaling in cell survival and induction of a Senescence-Associated Secretory Phenotype (SASP). To prove PD-1 signaling is critical to podocyte aging, aged mice were injected with anti-PD-1 antibody (aPD-1ab). Treatment significantly improved the aging phenotype in both kidney and liver. In the glomerulus, it increased the life-span of podocytes, but not parietal epithelial, mesangial or endothelial cells. Transcriptomic and immunohistochemistry studies demonstrate that anti-PD-1 treatment improved the health-span of podocytes. It restored the expression of canonical podocyte genes, transcription factors and gene regulatory networks, increased cellular metabolism signatures and lessened SASPs. These results suggest a critical contribution for increased PD-1 signaling towards both kidney and liver aging.

cell biology↗

bioRxiv2021

Profiling of Nascent Lariat Intermediates Reveals Key Genetic Determinants of the Timing of Human Co-transcriptional Splicing

As splicing is intimately coupled with transcription, understanding splicing mechanisms requires an understanding of splicing timing, which is currently limited. Here, we developed CoLa-seq (co-transcriptional lariat sequencing), a genomic assay that reports splicing timing relative to transcription through analysis of nascent lariat intermediates. In human cells, we mapped 165,282 branch points and characterized splicing timing for over 70,000 introns. Splicing timing varies dramatically across introns, with regulated introns splicing later than constitutive introns. Machine learning-based modeling revealed genetic elements predictive of splicing timing, notably the polypyrimidine tract, intron length, and regional GC content, which illustrate the significance of the broader genomic context of an intron and the impact of co-transcriptional splicing. The importance of the splicing factor U2AF in early splicing rationalizes surprising observations that most introns can splice independent of exon definition. Together, these findings establish a critical framework for investigating the mechanisms and regulation of co-transcriptional splicing. HighlightsO_LICoLa-seq enables cell-type specific, genome-wide branch point annotation with unprecedented efficiency. C_LIO_LICoLa-seq captures co-transcriptional splicing for tens of thousands of introns and reveals splicing timing varies dramatically across introns. C_LIO_LIModeling uncovers key genetic determinants of splicing timing, most notably regional GC content, intron length, and the polypyrimidine tract, the binding site for U2AF2. C_LIO_LIEarly splicing precedes transcription of a downstream 5 SS and in some cases accessibility of the upstream 3 SS, precluding exon definition. C_LI

molecular biology↗

bioRxiv2021

The maize gene maternal depression of r1 (mdr1) encodes a DNA glycosylase with maternal and paternal fertility functions

Demethylation of transposons can activate expression of nearby genes and cause imprinted gene expression in endosperm, and it is hypothesized to lead to expression of transposon siRNAs that reinforce silencing in the next generation through transfer either into egg or embryo. Here we describe maternal derepression of r1 (mdr1), which encodes a DNA glycosylase with homology to Arabidopsis DEMETER and which is partially responsible for demethylation of thousands of regions in endosperm. Instead of promoting siRNA expression in endosperm, MDR1 activity inhibits it. Methylation of most repetitive DNA elements in endosperm is not significantly affected by MDR1, with an exception of Helitrons. While maternally-expressed imprinted genes preferentially overlap with MDR1 demethylated regions, the majority of genes that overlap demethylated regions are not imprinted. Double mutant megagametophytes lacking both MDR1 and its close homolog DNG102 result in early seed failure, and double mutant microgametophytes fail pre-fertilization. These data establish DNA demethylation by glycosylases as essential in maize endosperm and pollen and suggest that neither transposon repression nor genomic imprinting are its main function in endosperm.

genetics↗

bioRxiv2021

Self-healing of hyaluronic acid to improve in vivo retention and function

Convergent advances in the field of soft matter, macromolecular chemistry, and engineering have led to the development of biomaterials that possess autonomous, adaptive, and self-healing characteristics similar to living systems. These rationally designed biomaterials could surpass the capabilities of their parent material. Herein, we describe the modification of hyaluronic acid (HA) molecules to exhibit self-healing properties and studied its physical and biological function both in vitro and in vivo. Our in vitro findings showed that self-healing HA designed to undergo autonomous repair improved lubrication, enhanced free radical scavenging, and resisted enzymatic degradation compared to unmodified HA. Longitudinal imaging following intra-articular injection of self-healing HA showed improved in vivo retention despite the low molecular weight. Concomitant with these functions, intra-articular injection of self-healing HA mitigated anterior cruciate ligament injury-mediated cartilage degeneration in rodents. This proof-of-concept study shows how incorporation of functional properties like self-healing can be used to surpass the existing capabilities of biolubricants.

bioengineering↗

bioRxiv2021

Modulation of the renin-angiotensin system inhibits memory advantage for negative emotional material via decreasing hippocampus activation and its coupling with the amygdala

Exaggerated arousal and dysregulated emotion-memory interactions are key pathological dysregulations that accompany the development of post-traumatic stress disorder (PTSD). Current treatments for PTSD are of moderate efficacy and preventing the dysregulations already during exposure to threatening events may attenuate the development of PTSD-symptomatology. In a preregistered double-blind, between-subject, placebo-controlled pharmaco-fMRI design, the present proof-of-concept study examined the potential of a single dose of angiotensin II type 1 receptor (AT1R) antagonist losartan (LT) to attenuate the mnemonic advantage of threatening stimuli and the underlying neural mechanism via combining an emotional subsequent memory paradigm with LT (n=29) or placebo treatment (n=30) and a surprise memory test after 24h washout. LT generally improved memory performance and abolished emotional memory enhancement for negative yet not positive material while emotional experience during encoding remained intact. LT further suppressed hippocampus activity during encoding of subsequently remembered negative stimuli. On the network level LT reduced coupling between hippocampus and basolateral amygdala during successful memory formation of negative stimuli. Our findings suggest that LT may have the potential to attenuate memory formation for negative yet not positive information by decreasing hippocampus activity and its functional coupling strength with amygdala. These findings suggest a promising potential of LT to prevent preferential encoding and remembering of negative events, a mechanism that could prevent the emotion-memory dysregulations underlying the development of PTSD-symptomatology.

neuroscience↗