Biology subjects

Liu, B.

Publications and source records attributed to Liu, B..

At least 145 records · Page 8Linked to original sources

bioRxiv2024

PM2.5 from Automobile Exhaust Induces Apoptosis in Male Rat Germ Cells via the ROS-UPRmt Signaling Pathway

ObjectiveTo explore the underlying mechanism behind the fine particulate matters (PM2.5)-mediated regulation of reproductive function in male rats, and to determine the role of vitamins in this process. MethodsIn all, 32 male SD rats were randomized to a control cohort (normal saline), a Vit cohort (vitamin C at 100 mg/kg + vitamin E at 50 mg/kg), a PM2.5 cohort (PM2.5 10 mg/kg), and a PM2.5+Vit cohort (PM2.5 exposure + vitamin C at 100 mg/kg + vitamin E at 50 mg/kg), with eight rats in each cohort. After four weeks of exposure, mating experiments were carried out. Thereafter, rats were euthanized, and the testis and epididymis tissues were excised for hematoxylin-eosin (HE) staining and sperm quality analysis. Apoptosis of testis tissues was quantified via a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the testicular oxidative stress (OS)-, apoptosis- and mitochondrial unfolded protein response (UPRmt)-related essential protein expressions were measured via western blotting (WB). ResultsAfter PM2.5 exposure, the sperm count and motility decreased, while sperm abnormality and the apoptosis index increased. HE staining showed that the number of spermatogenic cells decreased. WB showed that the PM2.5 group had decreased expressions of superoxide dismutase (SOD), nuclear factor E2-related factor 2 (Nrf2), and B-cell lymphoma-2 (Bcl-2) (p < 0.05), increased expressions of malondialdehyde (MDA), Bcl-2 associated X protein (Bax), and Caspase3 (p < 0.05), and downregulated expressions of C/EBP homologous protein (CHOP), heat shock protein 60 (HSP60), and activating transcription factor 5 (ATF5) (p < 0.05). These were all reversed by vitamin intervention. ConclusionPM2.5 from automobile exhaust disrupts male reproductive function. A combination of vitamins may protect reproductive function via the reactive oxygen species (ROS)-UPRmt signaling pathway. HighlightsO_LIPM2.5 from vehicle exhaust can cause apoptosis of male germ cells. C_LIO_LIPM2.5 from vehicle exhaust induces germ cell apoptosis through the ROS-UPRmt signaling pathway. C_LIO_LICombined vitamin C and E can enhance UPRmt activity to alleviate the germ cell apoptosis caused by PM2.5 from vehicle exhaust. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/621651v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@d3f5edorg.highwire.dtl.DTLVardef@1b6daa1org.highwire.dtl.DTLVardef@1cba0b4org.highwire.dtl.DTLVardef@1a3c9f1_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2024

Embryonic Mast Cells Arise from Cpa3-expressing Precursors Independent of Granulocyte-Monocyte Progenitors

Most of the mast cells (MCs) in connective tissues, such as skin, are long-lived embryonic-derived immune cells that play important roles in host defense and various immunological diseases, including allergies. Their embryonic origin and ontogeny remain to be fully studied since several overlapping waves of embryonic hematopoiesis have been shown to give rise to these cells. Here, combining single-cell RNA sequencing and new genetic fate mapping models, we identified a Cpa3-expressing population sequentially appearing in the yolk sac, fetal liver, and peripheral tissues which gives rise to dermal MCs during embryonic days 11.5 to 14.5. Using in vitro differentiation and in vivo transplant methods, we identified a Ter119-F4/80- CD45+CD117+CD16/32+CD135-CD115-Ly6C-CD34lo population as potential fetal liver MC precursors. Fate mapping with Cpa3CreERT2and Zbtb16CreERT2 models, as well as the granulocyte-monocyte progenitor (GMP) models Ms4a3Cre and ElaneCre, demonstrated that MCs arise from Cpa3+ progenitors rather than Ms4a3+ or Elane+ GMPs. A corresponding population with a similar developmental trajectory was also identified in human early yolk sac and fetal liver, suggesting a conserved MC developmental program across species. These findings delineate the detailed developmental path of MCs in embryos, permitting future functional studies in immunity and development. HighlightsO_LICpa3-expressing cells in the yolk sac and fetal liver contain mast cell precursors C_LIO_LICpa3CreERT2 labels embryonic mast cells and their precursors C_LIO_LIEmbryonic mast cells arise through Cpa3+ mast cell precursors, but not Elane+/Ms4a3+ GMPs C_LIO_LIThe seeding of MCPs to embryonic skin slows down after E14.5 C_LI

immunology↗

bioRxiv2024

Microsaccades strongly modulate but do not cause the N2pc EEG marker of spatial attention

The N2pc is a popular human-neuroscience marker of covert and internal spatial attention that occurs 200-300 ms after being prompted to shift attention - a time window also characterised by the spatial biasing of microsaccades. Here we show how co-occurring microsaccades profoundly modulate N2pc amplitude during the top-down deployment of spatial attention in both perception and working memory. At the same time, we show that a significant - even if severely weakened - N2pc can still be established in the absence of co-occurring microsaccades. Thus, while microsaccade presence and direction strongly modulate N2pc amplitude, microsaccades are not strictly a prerequisite for the N2pc to be observed.

neuroscience↗

bioRxiv2024

Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals

The origins of sex differences in human disease are elusive, in part because of difficulties in separating the effects of sex hormones and sex chromosomes. To separate these variables, we examined gene expression in four groups of trans- or cisgender individuals: XX individuals treated with exogenous testosterone (n=21), XY treated with exogenous estradiol (n=13), untreated XX (n=20), and untreated XY (n=15). We performed single-cell RNA-sequencing of 358,426 peripheral blood mononuclear cells. Across the autosomes, 8 genes responded with a significant change in expression to testosterone, 34 to estradiol, and 32 to sex chromosome complement with no overlap between the groups. No sex-chromosomal genes responded significantly to testosterone or estradiol, but X-linked genes responded to sex chromosome complement in a remarkably stable manner across cell types. Through leveraging a four-state study design, we successfully separated the independent actions of testosterone, estradiol, and sex chromosome complement on genome-wide gene expression in humans.

genomics↗

bioRxiv2024

Gut Microbial Impact on Colitis and Colitis-Associated Carcinogenesis in a Primary Sclerosing Cholangitis-IBD Model

Background and AimsPrimary sclerosing cholangitis (PSC) associated inflammatory bowel diseases (IBD) increase colorectal dysplasia and malignancy risk. Current mouse models do not adequately replicate human PSC-IBD, limiting mechanistic understanding and therapeutic development. This study uses Mdr2/Il10 double knockout (DKO) mice to examine microbiota roles in mediating colitis, colitis-associated colorectal dysplasia and hepatobiliary inflammation/fibrosis. GoalDevelop and phenotype a chronic spontaneous PSC-IBD mouse model, emphasizing colitis, colonic dysplasia, hepatobiliary inflammation/ fibrosis and the functional roles of resident microbiota. MethodsWe utilized germ-free (GF) and specific-pathogen-free Mdr2/Il10 DKO, Il10-/- and Mdr2-/- mice to model PSC-IBD. We monitored colonic dysplasia progression, colitis kinetics and severity by lipocalin-2, cytokine measurement, and tissue evaluations of colon and liver. We manipulated the microbiome to assess its functional effects. ResultsDKO mice exhibited age- and region-specific accelerated colitis and spontaneous colonic dysplasia progressing to high-grade invasive adenocarcinomas. Despite aggressive colonic inflammation, DKO mice showed reduced hepatic fibrosis, increased hepatic reparative macrophages, and matrix metalloproteinase activity compared to Mdr2-/- mice. GF DKO had heightened liver inflammation and mortality with absent colitis and colonic dysplasia, reversed with microbial reconstitution from DKO mice. Changes in DKO primary/secondary bile acid profiles mirrored those in PSC-IBD. ConclusionThe Mdr2/Il10 DKO model mirrors key factors in PSC-IBD patients in terms of inflammation and carcinogenesis. We found an important role for the dysbiotic microbiota in DKO mice for disease onset and progression. Targeting microbiota and bile acid metabolism may provide promising strategies for developing effective PSC-IBD therapies.

microbiology↗

bioRxiv2024

Endosomal hyper-acidification via proton-activated chloride channel deletion in neurons impairs AMPA receptor endocytosis and LTD

Endosomal homeostasis is critical for neuronal function, including the post-synaptic trafficking of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Dynamic AMPAR trafficking is a major component of synaptic plasticity, such as hippocampal long-term potentiation (LTP) and long-term depression (LTD) and is thought to be required for learning and memory. Dramatic alteration of endosomal pH has been reported to negatively affect synaptic transmission and neural development, but the underlying mechanisms by which pH is involved in AMPAR trafficking are unclear. Here, we show that the proton-activated chloride (PAC) channel localizes to early and recycling endosomes along neuronal dendrites and prevents hyper-acidification of endosomes. To directly measure AMPAR endocytosis, we used a new method to assess LTD using HaloTag-GluA2 and found that the loss of PAC reduces AMPAR internalization during chemical LTD in primary neurons, while AMPAR trafficking in unstimulated cells or during chemical LTP is unaffected. Consistently, pyramidal neuron-specific PAC knockout mice had impaired hippocampal LTD, but not LTP, and performed poorly in the Morris water maze reversal test, exhibiting an inability to adapt to changing environments (also referred to as behavioral flexibility). We conclude that proper maintenance of pH by PAC is important during LTD to regulate AMPAR trafficking in a manner critical for animal physiology and behavior. SummaryThe ability to adapt to changing environments stems from the plasticity of neurons, which can modulate their synaptic strength in response to neural activity. We discovered a novel mechanism by which an endosomal proton-activated chloride channel (PAC) is involved in synaptic weakening, or long-term depression (LTD). To improve tools used to study LTD, we developed a live-cell imaging assay to directly observe -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) endocytosis. PAC-deficient neurons have hyper-acidified endosomes and fail to endocytose AMPARs during LTD. Neuron-specific PAC knockout mice have impaired hippocampal LTD and fail to adapt to changes in their environment. The role of endosomal pH in synaptic function is understudied, and our results provide a novel mechanism whereby PAC can affect synaptic LTD.

neuroscience↗

bioRxiv2024

Simultaneous observation of Pol II and potato spindle tuber viroid RNA in the nucleus by combining immunofluorescence and RNA in situ hybridization

RNA is key component of a versatile group of complexes that play diverse roles in a wide range of biological processes, including plant acclimation to ever-changing environments. From synthesis to degradation, RNA molecules interact with cognate proteins that assist in processes such as transcription, splicing, modification, trafficking, and the execution of their functions. While numerous valuable techniques exist to study RNA-protein interactions, visualizing RNAs and their associated proteins simultaneously within cells remains challenging, despite its potential to provide deeper insights into the biology of RNA-protein interactions. In this study, we adapted a modified immunofluorescence (IF) assay in combination with RNA fluorescence in situ hybridization (FISH) to successfully visualize the colocalization of endogenous as well as infectious RNAs with their cognate binding proteins in plant nucleus. This new method that combines IF and FISH will facilitate future studies on RNA and protein colocalization in various plant systems.

plant biology↗

bioRxiv2024

Unveiling allopolyploidization-driven genome duplications through progressive analysis of deep genome skimming data

Whole-genome duplication (WGD) events are widespread across the Web of Life (WoL). Given the prevalence of WGDs in the polyploid Prunus (Rosaceae), this economically- and agriculturally-important angiosperm lineage provides an excellent model for exploring this mode of reticulation. We used the polyploid Prunus to demonstrate a progressive strategy for analyzing Deep Genome Skimming (DGS) data in the presence of WGDs. Phylogenomic discordance analyses indicated that allopolyploidization, rather than Incomplete Lineage Sorting (ILS), played a dominant role in the origin and dynamics of polyploid Prunus. This study underscores how a progressive strategy to identify WGD events at different depths in a phylogenetic tree reveals the nuances of evolutionary mechanisms driving allopolyploidization. We inferred that the continued uplift of the Himalayas from the Middle to Late Miocene drove the rapid diversification of the Eastern Asia endemic Maddenia clade, by facilitating frequent hybridization and allopolyploidization, specifically introgression between the Himalayas-Hengduan and the Central-Eastern China clades.

systems biology↗

bioRxiv2024

Small DNA elements that act as both insulators and silencers in plants

Insulators are cis-regulatory elements that separate transcriptional units, whereas silencers are elements that repress transcription regardless of their position. In plants, these elements remain largely uncharacterized. Here, we use the massively parallel reporter assay Plant STARR-seq with short fragments of eight large insulators to identify more than 100 fragments that block enhancer activity. The short fragments can be combined to generate more powerful insulators that abolish the capacity of the strong viral 35S enhancer to activate the 35S minimal promoter. Unexpectedly, when tested upstream of weak enhancers, these fragments act as silencers and repress transcription. Thus, these elements are capable of both insulating or repressing transcription dependent upon regulatory context. We validate our findings in stable transgenic Arabidopsis, maize, and rice plants. The short elements identified here should be useful building blocks for plant biotechnology efforts.

plant biology↗

bioRxiv2024

Tumorigencity decrease in Bcl-xL deficient MDCK cells ensuring the safety for influenza vaccine production

Madin-Darby canine kidney (MDCK) cells are the recognized cell strain for influenza vaccine production. However, the tumorigenic potential of MDCK cells raises concerns about their use in biological product manufacturing. To reduce MDCK cells tumorigenicity and ensure the safety of influenza vaccine production, a B-cell lymphoma extra-large (Bcl-xL) gene, which plays a pivotal role in apoptosis regulation, was knocked-out in original MDCK cells by CRISPR-Cas9 gene editing technology, so that a homozygous MDCK-Bcl-xL-/- cell strain was acquired and named as BY-02. Compared with original MDCK cells, the proliferation and migration ability of BY-02 were significantly reduced, while apoptosis level was significantly increased, the endogenous mitochondrial apoptotic pathway were also modulated after Bcl-xL knock-out in MDCK cells. For tumor formation assays in nude mouse tests, all ten mice injected with original MDCK cells presented tumors growth in the injection site, in contrast to only one mouse injected with BY-02 cells presented tumors growth. These findings suggest that Bcl-xL knock-down is an effective strategy to inhibit tumor formation in MDCK cells, making BY-02 a promising genetically engineered cell strain for influenza vaccine production.

cell biology↗

bioRxiv2024

A brainstem circuit controls cough-like airway defensive behaviors in mice

The respiratory tract is subject to complex neural control for eupneic breathing and distinct airway defensive reflexes. Growing evidence has highlighted significant heterogeneity of airway-innervating vagal sensory neurons in mediating various respiratory functions, however, the central neuronal pathways and neural circuits involved in the airway regulation remain less understood. Combining whole-body plethysmography (WBP), audio, and video tracking to access breathing and airway defensive behaviors in conscious animals, we developed a quantitative paradigm implementing the mouse as a model to study cough-like defensive behaviors. Using TRAP2 transgenic mice and in vivo fiber photometry, we found that the neural activity in the caudal spinal trigeminal nucleus (SP5C) is strongly correlated with tussigen-evoked cough-like responses. Impairing synaptic outputs or chemogenetic inhibition of the SP5C effectively abolished these cough-like reflexes. Optogenetic stimulation of SP5C excitatory neurons or their projections to the ventral respiratory group (VRG) triggered robust cough-like behaviors without tussive stimuli. Notably, tonic elevation of SP5C excitability caused spontaneous cough-like activities chronically in mice. Together, our data provide strong evidence for a previously unrecognized brainstem circuit that controls cough-like defensive behaviors in mice.

neuroscience↗

bioRxiv2024

Cis-regulatory elements driving motor neuron-restricted viral payload expression within the mammalian spinal cord

Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant movement disorders. Despite the recent approval of gene therapeutics targeting these MN-related disorders, there are no viral delivery mechanisms that achieve MN-restricted transgene expression. In this study, chromatin accessibility profiling of genetically defined mouse MNs was used to identify candidate cis-regulatory elements (CREs) capable of driving MN-selective gene expression. Subsequent testing of these candidates identified two CREs that confer MN-selective gene expression in the spinal cord as well as reduced off-target expression in dorsal root ganglia. Within one of these candidate elements, we identified a compact core transcription factor (TF)-binding region that drives MN-selective gene expression. Finally, we demonstrate that selective spinal cord expression of this mouse CRE is preserved in non-human primates. These findings suggest that the generation of cell-type-selective viral reagents, in which cell-type-selective CREs drive restricted gene expression, will be valuable research tools in mice and other mammalian species, with potentially significant therapeutic value in humans. SIGNIFICANCE STATEMENTMotor neurons transduce the motor outputs of nervous system activity to muscle and are the vulnerable neurons in a number of clinically significant degenerative conditions, including spinal muscular atrophy and amyotrophic lateral sclerosis. A recent strategy for treating motor neuron degenerative diseases has been to use viruses to introduce genes into motor neurons to inhibit the degenerative process. However, we still lack viral reagents that promote gene expression in motor neurons without potentially toxic off-target expression in other cell types. Our study identifies cis-regulatory elements capable of conferring motor neuron-selective transgene expression in a viral context. These findings have important implications for future gene therapeutics for motor neuron-related disorders.

neuroscience↗

bioRxiv2024

PBAE-PEG based lipid nanoparticles for lung cell-specific gene delivery

Delivery of modified mRNA encapsulated in lipid nanoparticles, exemplified by their successful use in COVID-19 vaccination, provides a framework for treating various genetic and acquired disorders. Herein, we developed PEGylated(PBAE-PEG) and non-PEGylated(PBAE) PBAE with lipids 4A3-SC8/DOPE/cholesterol/DOTAP to form lipid nanoparticles (LNPs) for mRNA delivery into different types of pulmonary cells in vivo. PBAE-PEG/LNP were highly active in transfecting HEK293T cells and air-liquid interfaced H441 cells in vitro. PBAE-PEG/LNP were used to express Cre-recombinase after administration to mice by intravenous injection, resulting in high transfection levels in pulmonary vascular endothelial cells. Intratracheal injection of both PBAE-PEG/LNP and PBAE/LNPs resulted in efficient and selective transfection of lung epithelial cells, identified by the expression of stabilized Cre-recombinase mRNA in club cells and alveolar type 2 cells. PBAE-PEG/LNP were most effective in transfecting alveolar type 2 cells after intratracheal injection, while PBAE/LNPs administered intratracheally were more effective in transfecting secretory airway cells. Cre-mediated recombination was specific to lung epithelial cells after intratracheal administration. Likewise, intravenous administration resulted in selective transfection of endothelial cells but not other pulmonary cell types, indicating their failure to cross the pulmonary endothelial-to-epithelial barrier. Moreover, 5-methoxyuridine modified mRNA was more efficient than unmodified mRNA in vivo but not in vitro.

bioengineering↗

bioRxiv2024

Myeloid-Specific Thrombospondin-1 Deficiency Exacerbates Aortic Rupture via Broad Suppression of Extracellular Matrix Proteins

RationaleRupture of abdominal aortic aneurysms (AAA) is associated with high mortality. However, the precise molecular and cellular drivers of AAA rupture remain elusive. Our prior study showed that global and myeloid-specific deletion of matricellular protein thrombospondin-1 (TSP1) protects mice from aneurysm formation primarily by inhibiting vascular inflammation. ObjectiveTo investigate the cellular and molecular mechanisms that drive AAA rupture by testing how TSP1 deficiency in different cell populations affects the rupture event. Methods and ResultsWe deleted TSP1 in endothelial cells and macrophages --- the major TSP1-expressing cells in aneurysmal tissues ---- by crossbreeding Thbs1 flox/flox mice with VE-cadherin Cre and Lyz2-cre mice, respectively. Aortic aneurysm and rupture were induced by angiotensin II in mice with hypercholesterolemia. Myeloid-specific Thbs1 knockout, but not endothelial-specific knockout, increased the rate of lethal aortic rupture by more than 2 folds. Combined analyses of single-cell RNA sequencing and histology showed a unique cellular and molecular signature of the rupture-prone aorta that was characterized by a broad suppression in inflammation and extracellular matrix production. Visium spatial transcriptomic analysis on human AAA tissues showed a correlation between low TSP1 expression and aortic dissection. ConclusionsTSP1 expression by myeloid cells negatively regulates aneurysm rupture, likely through promoting the matrix repair phenotypes of vascular smooth muscle cells thereby increasing the strength of the vascular wall.

pathology↗

bioRxiv2024

Unraveling the Web of Life: Incomplete lineage sorting and hybridization as primary mechanisms over polyploidization in the evolutionary dynamics of pear species

In contrast to the traditional Tree of Life (ToL) paradigm, the Web of Life (WoL) model provides a more nuanced and precise depiction of organismal phylogeny, particularly considering the prevalent incongruence observed among gene/species trees. The lack of a generalized pipeline for teasing apart potential evolutionary mechanisms--such as Incomplete Lineage Sorting (ILS), hybridization, introgression, polyploidization, and Whole-Genome Duplication--poses significant challenges to the delineation of the WoL. The pear genus Pyrus, characterized by extensive hybridization events, serves as an excellent model for investigating the WoL. This study introduces a novel Step-by-Step Exclusion (SSE) approach to deciphering the complexities inherent in the WoL. Our findings indicate: 1) ILS, rather than polyploidization, is identified as the primary driver behind the origin of Pyrus from the arid regions of the Himalayas-Central Asia; 2) the two subgenera of Pyrus have independent evolutionary trajectories, facilitated by the geographical barriers that arose via the uplift of the Tibetan Plateau and increased aridity in Central Asia; 3) ILS and hybridization have facilitated the diversification of Oriental pears, while hybridization alone has driven the reticulate evolution of Occidental pears; 4) the establishment of the Silk Road during the Han Dynasty acted as a conduit for genetic exchange between Occidental and Oriental pears. The novel SSE approach provides a universally applicable framework for investigating evolutionary mechanisms defining the WoL paradigm.

systems biology↗

bioRxiv2024

Harnessing in vivo Synthesis of Bioactive Multiarylmethanes in Escherichia coli via Oxygen-Mediated Free Radical Reaction Induced by Simple Phenols

BackgroundXanthenes and multi-aryl carbon core containing compounds represent different types of complex and condensed architectures that have impressive wide range of pharmacological, industrial and synthetic applications. Moreover, indoles as building blocks were only found in naturally occurring metabolites with di-aryl carbon cores and in chemically synthesized tri-aryl carbon core containing compounds. Up to date, rare xanthenes with indole bearing multicaryl carbon core have been reported in natural or synthetic products. The underlying mechanism of fluores-cein-like arthrocolins with tetra-arylmethyl core were synthesized in an engineered Escherichia coli fed with toluquinol remained unclear. ResultsIn this study, the Keio collection of single gene knockout strains of 3901 mutants of E. coli BW25113, together with 14 distinct E. coli strains, was applied to explore the origins of endoge-nous building blocks and the biogenesis for arthrocolin assemblage. Deficiency in bacterial res-piratory and aromatic compound degradation genes ubiX, cydB, sucA and ssuE inhibited the mu-tant growth fed with toluquinol. Metabolomics of the cultures of 3897 mutants revealed that only disruption of tnaA involving in transforming tryptophan to indole, resulted in absence of arthro-colins. Further media optimization, thermal cell killing and cell free analysis indicated that a non-enzyme reaction was involved in the arthrocolin biosynthesis in E. coli. Evaluation of redox potentials and free radicals suggested that an oxygen-mediated free radical reaction was respon-sible for arthrocolins formation in E. coli. Regulation of oxygen combined with distinct phenol derivatives as inducer, 31 arylmethyl core containing metabolites including 13 new and 8 biolog-ical active, were isolated and characterized. Among them, novel arthrocolins with p-hydroxylbenzene ring from tyrosine were achieved through large scale of aerobic fermentation and elucidated x-ray diffraction analysis. Moreover, most of the known compounds in this study were for the first time synthesized in a microbe instead of chemical synthesis. Through feeding the rat with toluquinol after colonizing the intestines of rat with E. coli, arthrocolins also ap-peared in the rat blood. ConclusionOur findings provide a mechanistic insight into in vivo synthesis of complex and condensed ar-throcolins induced by simple phenols and exploits a quinol based method to generate endoge-nous aromatic building blocks, as well as a methylidene unit, for the bacteria-facilitated synthesis of multiarylmethanes.

biochemistry↗

bioRxiv2024

Longevity or Well-being? A Dual-Dimension Structure of Neuroticism

The development of personality traits is often viewed as evolutionarily adaptive. Current neuroticism research, however, predominantly highlights its negative health impacts, neglecting its potential evolutionary advantages. We propose that neuroticisms inter-individual variability can be structured into two distinct geometric dimensions. One, named the Emotional Reactivity-Instability/Distress Spectrum (ERIS), correlates strongly with longevity and is associated with chronic diseases and risk-averse lifestyle. This dimension is underpinned by evolutionarily conserved subcortical brain regions and genes. The other, resembling the overall neuroticism score, is primarily linked to mental and stress-related disorders, as well as life satisfaction. It involves higher-order emotional brain regions and is genetically enriched in human-accelerated regions. Collectively, these dimensions represent a dual-strategy personality framework that optimizes survival and well-being, with the former being evolutionarily conservative and the latter potentially a unique human adaptation.

neuroscience↗

bioRxiv2024

TDSTDP

This is a preliminary thesis on Temporal Difference Spike-Timing Dependent Plasticity (TDSTDP), a variation of STDP that considers dendritic potential. TDSTDP is capable of performing temporal difference (TD) learning without dopamine modulation. Major characteristics of TD learning, including value estimation, value propagation, and temporal shifting of dopamine, are demonstrated in simulations. Additionally, a synaptic calcium model demonstrates its biological plausibility.

neuroscience↗