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Cheng, Z.

Publications and source records attributed to Cheng, Z..

At least 37 records · Page 2Linked to original sources

Inferring unobserved vector dynamics for dengue forecasting using physics-informed neural networks and mechanistic transmission models

Accurately characterising mosquito infection dynamics is essential for effective dengue prevention and control, yet these dynamics are rarely observable through routine surveillance. Here, we integrate a reduced SI-SIR transmission model with monthly dengue incidence data using physics-informed neural networks (PINNs) to develop a Dengue-Informed Neural Network (DINN). The DINN simultaneously fits reported dengue cases from 15 countries between January 2014 to April 2025 and reconstructs the unobserved time series of infected mosquitoes. Using the inferred mosquito infection dynamics together with five-month-lagged climatic variables, we subsequently train recurrent neural networks (RNN, GRU and LSTM) to forecast mosquito infection levels one month ahead. For each country, the optimal forecasting model is selected based on out-of-sample performance, and model behaviour is interpreted using SHAP analysis. We show that the DINN captures multi-wave outbreak dynamics across diverse epidemic regions and enables the development of country-specific vector forecasting models. When integrated with the transmission model, the predicted mosquito trajectories support two-year projections of dengue incidence, providing a quantitative framework for early warning and evidence-based control strategies. Author summaryMechanistic models of dengue transmission often require assumptions about mosquito population sizes and temperature-dependent biological traits that are difficult to specify accurately and rarely observed in practice. These limitations can reduce the reliability of outbreak prediction and hinder the evaluation of control strategies. Here, we introduce a Dengue-Informed Neural Network (DINN) that integrates deep learning with a reduced SI-SIR transmission model to address these challenges. Without requiring prior specification of mosquito initial conditions or biological trait functions, DINN infers latent time series of infectious mosquitoes directly from reported human case data and reconstructs complex, multi-wave transmission dynamics. Applying this approach to dengue surveillance data from 15 countries, we uncover substantial regional variation in inferred mosquito infection patterns, reflecting differences in environmental variability and vector control. By combining the inferred mosquito dynamics with climatic information, we further develop interpretable forecasting models and generate two-year projections of dengue incidence. Our results demonstrate that DINN provides a flexible and interpretable framework for inferring unobserved vector dynamics and offers practical support for early warning and evidence-based control of mosquito-borne diseases.

ecology↗

In Vivo Cardiac Prime Editing Corrects the Pathogenic Mutation and Rescues Cardiomyopathy Phenotypes in a Novel Humanized RBM20 Mouse Model

Heart disease affects millions of individuals and prime editing (PE) may enable curative therapies that address the underlying drivers of heart disease. Here we describe the establishment and optimization of an in vivo cardiac PE platform which mediates efficient editing in the heart with no detectable editing in the liver. We performed a proof-of-concept test on RNA binding motif protein 20 (RBM20), which if mutated, can cause dilated cardiomyopathy (DCM) in humans. Our dual-AAV based PE therapeutic rescued cardiomyopathy phenotypes in the heterozygous Rbm20R636Q mouse model. To further develop PE targeting human RBM20, we introduced a novel humanized mouse model carrying human RBM20 wildtype (WT) or R634Q mutant sequences and displaying RBM20 cardiomyopathy phenotypes. Our human RBM20 PE therapeutic efficiently corrected the pathogenic mutation and rescued phenotypes in the humanized RBM20 mouse model. Our findings demonstrate the potential of in vivo cardiac PE in treating heart disease, offer a valuable humanized DCM mouse model for developing various therapies, and present an optimized in vivo PE platform that can be adopted for targeting other organs and tissues.

bioengineering↗

Hierarchy in neuronal representations of multiple tasks in prefrontal cortex

The ability to perform multiple tasks is one of the fundamental hallmarks of general intelligence in the brain. However, the underlying neural mechanisms remain largely unknown. We trained macaque monkeys to perform four tasks with identical spatial layouts but different cognitive demands, and recorded activities of thousands of prefrontal neurons using two-photon calcium imaging. Within the same neuronal population, we identified a multitask neural geometry composed of multiple low-dimensional subtask spaces, each encoding spatial information within a specific subtask. These subtask spaces shared a ring-like representational structure, forming a generalized spatial code across different subtasks. Task separation arose from separable bases and offsets of subtask spaces, modulated primarily by meta-task features. Thus, the neural geometry is organized by a three-level hierarchical structure: location codes are nested within subtask spaces, which are grouped as different meta-tasks. This hierarchy supported generalization across both locations and tasks, and explained monkeys error behaviors. Together, the hierarchically organized neural geometry underlies flexible multitask behavior.

neuroscience↗

Coordinate Up-regulation of Both TK1 and TS Expression in Cycling Cells: Mechanistic Basis and Implications for Dual-Targeted Cancer Therapy

Our previous study [2] has revealed that various types of cycling cells undergo rapid proliferation and division. Cycling cells can be broadly categorized into two groups: cycling immune cells (CICs) and cycling non-immune cells (CNICs). Cancer cells represent a special type of cycling cells. Based on a set of 26 marker genes, we proposed a simple method for the rapid identification of cycling-cell types. Comparisons across cycling-cell types uncovered novel gene-regulatory mechanisms underlying the cell cycle, development, and differentiation. Notably, we discovered that the coordinate up-regulation of both TS and TK1 expression is indispensable for securing a robust deoxythymidine triphosphate (dTTP) supply required for DNA replication in cycling cells. The compensatory interplay between salvage and de novo synthesis provides a plausible explanation for resistance to 5-fluorouracil (5-FU), a TS inhibitor for cancer chemotherapy. Consequently, blocking dTTP synthesis requires co-inhibition of TK1 and TS. For the first time, we present the crucial single-cell transcriptome evidence for this coordinate up-regulation, thereby establishing the mechanistic basis for developing TK1/TS as a dual target in cancer therapy.

cancer biology↗

In situ cryo-ET reveals restricted docking of intraflagellar transport at the base of the trypanosome flagellum

Cilia and flagella are conserved organelles essential for sensory and motility functions and are assembled and maintained by bidirectional intraflagellar transport (IFT) along the axoneme. In Trypanosoma brucei, IFT is concentrated at the flagellar base near the transition zone and is restricted to four microtubule doublets (MTDs) as it traverses from the transition zone to the axoneme before reaching the extra-axonemal structure, the paraflagellar rod (PFR), associated region. To gain an insight on its initial working model before IFT restriction occurs, we revealed the in situ architecture of the IFT complex during the initial and complete landing to the transition zone using cryo-focused ion beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET). IFT proteins assemble into polymeric trains upon landing. However, in the proximal portion of the flagellum, subtomogram averaging revealed that each single train is associated with individual MTDs at variable A- or B-tubule positions. By using miniaturized and enucleated T. brucei zoids that preserve the full circular arrangement of MTDs without milling, we revealed an alternating but spatially restricted IFT train pattern during the landing process, resembling the anterograde train scaffold known in Chlamydomonas. Magnify expansion microscopy further confirmed this restricted distribution of IFT proteins at the basal pool. Depletion of the IFT component IFT46 protein reduced the number of simultaneously docked trains without altering the restricted landing spatial pattern. These findings reveal a previously unrecognized spatial regulation governing IFT train initiation at the flagellar base, which could operate independently of IFT-B structural integrity, bridging the gap between the IFT architecture and doublet-spatial docking prior to anterograde transport.

cell biology↗

Absence of MBP 3' UTR in Mice Disrupts mRNA Transport, Myelination, and Motor Learning

Myelin sheath maturation requires compaction, a cellular phenomenon mediated by local translation of myelin basic protein (MBP), which acts as a molecular zipper to join adjacent membranes and extrude the cytoplasm. Contrary to decades-old microinjection experiments indicating that Mbp mRNA transport is restricted to microtubules, we now show using smFISH that endogenous Mbp mRNA granules indeed localize along actin. To validate the in vivo necessity of Mbp mRNA transport and its dependence on the 3 UTR (untranslated region), we replaced the endogenous Mbp 3 UTR with polyA tail sequences. Though these mice have decreased Mbp mRNA levels, this alone could not account for their striking phenotypes - hypomyelination, baseline tremors, and motor learning defects. Thus, we cultured oligodendrocytes from these mice and found defects in both Mbp mRNA localization and local translation. These results demonstrate that the 3 UTR of a locally translated structural protein is critical for both developmental and activity-induced myelination.

cell biology↗

The Notch/snRNA negative feedback regulation and its implications in Alzheimer's disease

Alzheimers disease (AD) is a multifactorial disorder whose hallmark lesions have been recognized for more than a century, yet its molecular pathobiology remains fragmentary. During our AD research, we discovered a direct mechanistic axis that links the Notch signalling pathway -- a crucial regulator of cell differentiation and proliferation--with the small nuclear RNAs (snRNAs) that drive pre-mRNA splicing. For the first time, our discovery unifies two previously siloed paradigms -- cell signal transduction and RNA splicing, expanding the fundamental knowledge of gene expression and its regulation. The first contribution of the present study is the discovery and validation of the Notch/snRNA negative feedback regulation. More implications include: (1) it reframes splicing-related diseases as dynamic consequences of pathway dysregulation rather than static snRNA-gene mutations; (2) it explains why global splicing abnormalities appear in AD, aging, and cancer even when snRNA genes themselves are not mutated; and (3) it provides an immediate, druggable "splicing rheostat" for any Notch-hyperactive disorder, such as AD.

cell biology↗

In vivo imaging of reactive oxygen species after myocardial ischemia-reperfusion injury: a large animal multimodal imaging and transcriptomic study

BackgroundReactive oxygen species (ROS) contribute to myocardial ischemia-reperfusion injury (IRI), but in-vivo data on the spatial myocardial distribution and systemic effects of ROS after IRI remain limited. This multimodal CMR and PET/CT study aimed to non-invasively image ROS activity in a clinically-relevant swine model of IRI using [18F]ROStrace, a fluorine-18-labeled analogue of dihydroethidium (DHE), and to investigate regional changes in ROS activity in the infarcted myocardium during the subacute post-IRI phase. MethodsIRI was induced by percutaneous occlusion of the left anterior descending artery for 90 minutes in swine (N=9). CMR and whole-body PET/CT imaging with [18F]ROStrace were performed before myocardial infarction (MI) and 3-5 days post-MI to assess ROS in non-infarct myocardium, lungs, bone marrow, spleen and skeletal muscle. Late gadolinium enhanced CMR was performed to structurally characterize infarct regions. Post-MI, in vivo [18F]ROStrace signal in infarcted myocardium was compared with remote, non-infarcted myocardium and validated via ex vivo DHE fluorescent imaging. Bulk RNA-sequencing (RNA-seq) and Gene Ontology pathway analysis were conducted on biopsies from infarct and remote myocardial tissue to identify differentially expressed genes and pathways connected to oxidative stress. ResultsDuring the subacute phase following MI, [18F]ROStrace fractional uptake rate (FUR; min-1) was significantly increased in skeletal muscle, compared to baseline (0.011{+/-}0.003 vs 0.016{+/-}0.005, p=0.04), with a trend toward increased FUR in bone marrow (0.046{+/-}0.009 vs 0.056{+/-}0.011, p=0.12) and the left ventricular free wall (0.067{+/-}0.007 vs 0.073{+/-}0.010, p=0.15). Within the myocardium, [18F]ROStrace FUR ((min-1)/(mL/min/g)) was significantly higher in infarcted compared to non-infarcted myocardium regions (0.110{+/-}0.034, vs 0.148{+/-}0.035, p=0.0005). DHE staining confirmed elevated ROS levels in the infarcted myocardium. RNA-seq identified 8,707 differentially expressed genes between infarct and remote myocardium, with downregulated pathways in the infarct associated with mitochondrial function, cellular respiration, and metabolic adaptation. ConclusionThis study demonstrated MI ROS imaging using [18F]ROStrace using a whole-body PET/CT scanner and structural assessment with CMR. Systemic and myocardial increases in ROS activity were observed post-MI, accompanied by substantial molecular alterations in infarcted tissue. These findings show potential imaging strategies to evaluate therapeutic targets that can mitigate oxidative stress after MI.

bioengineering↗

High throughput quantitative tracking of single parasite in Plasmodium falciparum

New systematic profiling of drug effects is in demand due to limitations in existing approaches to evaluate comprehensive drug effects and distinguish heterogeneity in mixed populations. One challenge is the underdeveloped methods for investigation of causal association between artemisinin induced dormancy and recrudescence in Plasmodium falciparum. We developed Quantitative Tracking After Chemotherapy Exposure (qTRACE) and an artificial intelligence (AI) mode to evaluate cytotoxic and cytostatic effects simultaneously at single parasite resolution in a high throughput platform. qTRACE is based upon the observation that individual parasites grow into colonies that can be quantified for numbers of viability and growth rate. Applying qTRACE, we revealed parasite-drug killing dynamics after artemisinin exposure, finding up to 50% of viable parasites arise directly from recovery of artemisinin induced dormancy. We further developed next generation qTRACE integrated with deep learning-based segmentation and analysis, thereby directly linking continuous, time-lapse phenotypes of label-free live P. falciparum. Our results confirmed the viability of dormant ring stages and that recovery rates differ between artemisinin-susceptible and -resistant P. falciparum.

cell biology↗

Metal Ion-Releasing Glass Particles to Enhance Antibiotic Efficacy Against Cystic Fibrosis Infection

Cystic fibrosis is characterized by thickened airway mucus that impairs mucociliary clearance and promotes persistent bacterial infections. These chronic infections, primarily caused by Pseudomonas aeruginosa and Staphylococcus aureus, lead to progressive lung damage and respiratory failure, which are the leading causes of mortality in cystic fibrosis patients. Although antibiotics remain the cornerstone of treatment for such airway infections, incomplete bacterial eradication often contributes to the emergence of antibiotic resistance. This study explores whether the efficacy of conventional antibiotics can be enhanced through co-delivery with antibacterial metal ions released from borate-based bioactive glasses. To evaluate this combination therapy, we developed an in vitro airway infection model that replicates key features of the cystic fibrosis airway environment. The model incorporates a layer of bronchial epithelial cells, a mucus-like hydrogel, and bacteria deposited using an aqueous two-phase system. Multiple bioactive glass formulations were evaluated for their ability to augment antibiotic activity and enhance bacterial eradication. The results demonstrated additive or synergistic antibacterial effects against P. aeruginosa and S. aureus, while maintaining mammalian cell viability. These findings suggest that metal ion-antibiotic combination therapies delivered via bioactive glasses may improve treatment outcomes for cystic fibrosis-related infections and reduce reliance on high-dose or prolonged antibiotic regimens. Such approaches hold promise not only for cystic fibrosis patients but also for broader clinical applications where antibiotic resistance is a growing concern.

bioengineering↗

Inhibition of CGRP receptor ameliorates AD pathology by reprogramming lipid metabolism through HDAC11/LXRβ/ABCA1 signaling

The Calcitonin gene-related peptide (CGRP) receptor has gained attention in Alzheimers Disease (AD) research due to its involvement in regulating neuroinflammation. However, its role and mechanism in AD pathology remain unclear. Here, we demonstrate that CALCRL, a core component of the CGRP receptor, is upregulated in the hippocampus of AD dementia patients and 5xFAD mice. Knockout of the CGRP receptor ligand Calca or pharmacological blockade using Rimegepant (Rim), reduces soluble A{beta}1-42 oligomer-induced neuronal death and glial inflammation. Rim treatment also rescues neurobehavioral impairments, neurodegeneration, and lipid metabolism dysfunction in 5xFAD mice. Mechanistically, these effects are mediated through HDAC11 inhibition, which enhances LXR{beta} acetylation and ABCA1 expression, promoting the reprogramming of neuronal lipid metabolism. Importantly, this CALCRL/HDAC11/LXR{beta}/ABCA1 axis is conserved across both humans and mice. Our findings uncover a novel mechanism underlying AD pathogenesis and highlight the therapeutic potential of targeting CGRP signaling in AD. HIGHLIGHTSInhibition of CGRP receptor ameliorates disease pathology in models of AD HDAC11 mediates CGRP receptor function in AD HDAC11 is a pivotal regulator in lipid metabolism by LXR{beta}/ABCA1 signaling The HDAC11/LXR{beta}/ABCA1 axis is conserved in AD humans and mice

neuroscience↗

Macrophages display spatiotemporal specificity in intrahepatic cholangiocarcinoma and drive tumour progression via OSM and THBS1

Tumor-associated macrophages (TAMs) are abundant in intrahepatic cholangiocarcinoma (ICC) and correlate with poor prognosis, but their non-immunosuppressive roles remain unclear. This study aimed to define TAM transcriptional heterogeneity and map their interactions with ICC cells that promote malignancy beyond immune suppression. Single-cell and spatial transcriptome analysis with mouse and human ICC tissues revealed a TAM subpopulation, designated M{varphi}_VEGFA, that emerged as the major macrophage population from the intermediate stage of ICC development onward. Data from Gene Expression Omnibus (GEO) and spatial transcriptome indicate that M{varphi}_VEGFA was associated with poor prognosis and spatially localized to the ICC cells. Cell co-culture and cell-cell communication analyses revealed that M{varphi}_VEGFA promoted ICC cell proliferation via secreted OSM and downstream OSMR-STAT3-CCND1 axis, and enhanced ICC cell invasion through THBS1 and downstream CD47-mTOR/DBN1 signaling. Critically, multiplex immunofluorescence with human ICC tissue microarray indicated that OSM and THBS1 were co-elevated in human ICCs, and dual blockade of both targets inhibited ICC progression in mouse models. This study uncovers the direct and critical roles of M{varphi}_VEGFA in driving ICC progression with paracrine signaling and further highlights the potential of targeting macrophages in ICC treatment.

cancer biology↗

Pancreatic tumor microenvironment reprogramming via alloantigen-expressing virotherapy elicits tumor rejection and improves immunotherapy response

Pancreatic ductal adenocarcinoma (PDAC), the most common malignant type of pancreatic cancer, is characterized by a dense desmoplastic stroma, low neoantigen burden, and a highly immunosuppressive tumor microenvironment (TME), which severely limit cytotoxic T-cell infiltration and the efficacy of immune therapies. Here, we present a novel strategy harnessing acute transplant rejection mechanisms by employing a recombinant oncolytic rVMG vector engineered to express the murine H-2Kk MHC class I alloantigen (rVMG-H-2Kk), thereby inducing tumor-specific antigenic mismatch responses. In vitro, rVMG-H-2Kk exhibited strong replication and cytolytic activity while inducing cell surface expression of both H-2Kk and endogenous H-2Kb, in addition to upregulation of antigen presentation genes ({beta}2-microglobulin, Tap1, and Tapbp). In two independent immunocompetent PDAC models, intratumoral and systemic delivery of rVMG-H-2Kk delayed tumor progression and prolonged survival. Multiplex immunohistochemistry and immunophenotyping revealed substantial TME remodeling, marked by increased effector T-cell infiltration, regulatory T-cell depletion, and reduced fibrosis. Spatial transcriptomics further showed compartment-specific immune activation and epithelial metabolic reprogramming, corroborating with enhanced tumor immunogenicity. Despite these effects, rVMG-H-2Kk also induced compensatory immunosuppressive pathways, including upregulation of antiviral response genes and immune checkpoint receptors such as PDL-2. Importantly, combination therapy with rVMG-H-2Kk and murine checkpoint blockade (anti-PD-1 and anti-CTLA-4) drastically improved survival than checkpoint blockade alone. Strikingly, surviving mice resisted tumor rechallenge, indicating the establishment of durable antitumor memory. Collectively, these findings establish rVMG-H-2Kk as a novel immunotherapeutic platform capable of converting immune-cold tumors into immune-hot, sensitizing tumors to immune checkpoint inhibitors, and establishing durable antitumor immunity in PDAC. One Sentence SummaryOncolytic virus-based delivery of an alloantigen improves antitumor immunity and synergizes with immune checkpoint inhibitors in pancreatic cancer. Significance statementDelivery of murine alloantigens via an engineered oncolytic vesiculovirus, combined with immune checkpoint blockade, overcomes immunosuppressive barriers and establishes durable antitumor immunity in PDAC.

cancer biology↗

Maximized field-of-view deep-brain calcium imaging through gradient-index lenses

Advances in genetically encoded fluorescent indicators have enabled increasingly sensitive optical recordings of neural activity. However, light scattering in the mammalian brain tissue restricts optical access to deeper regions. To address this limitation, researchers often employ implanted gradient-index (GRIN) lenses to reach deep brain areas. Nevertheless, the severe optical aberrations of GRIN lenses significantly reduce the effective field of view (FOV). In this work, we present a simple and robust imaging approach that combines low-NA telecentric scanning (LNTS) of laser excitation with high-NA fluorescence collection to increase the FOV. This configuration effectively eliminates common aberrations such as astigmatism and field curvature, resulting in a FOV [~]100% as large as the GRIN lens facet area -- corresponding to a [~]400% increase in imaging area compared with conventional approaches. We validate this method through both structural and functional in vivo imaging. The highly consistent imaging performance, fully maximized imaging FOV, and the very simple optical design make this method well-suited for broad dissemination in neuroscience research.

neuroscience↗

Hepatocyte FAM210A deficiency disrupts mitochondrial function and triggers juvenile steatosis with compensatory repair in adulthood

Mitochondrial dynamics are central to maintaining liver metabolic homeostasis, yet the mechanisms that safeguarding mitochondrial integrity during development and metabolic dysfunction remain poorly defined. Here, we identify Family with sequence similarity 210 member A (FAM210A) as a hepatocyte-enriched mitochondrial regulator essential for postnatal liver maturation. Hepatocyte-specific deletion of Fam210a (Fam210aHKO) in mice caused early growth restriction, reduced body and liver mass, and pronounced hepatic steatosis with glycogen depletion. These defects were accompanied by lower postprandial glucose levels in the fasted-refeeding state, impaired oxidative phosphorylation, reduced mtDNA content, and abnormal cristae architecture. Transcriptomic and proteomic profiling revealed broad suppression of fatty acid, sterol, and bile acid metabolism, with concomitant glutathione stress responses. Mechanistically, FAM210A deficiency disrupted the YME1L-OPA1 axis, driving excessive OPA1 cleavage and cristae destabilization. Strikingly, these juvenile defects were transient and resolved by adulthood, underpinned by enhanced hepatocyte proliferation and mitochondrial biogenesis, consistent with a compensatory stress-adaptive response via the activation of ISR signaling. Together, these findings uncover FAM210A as a developmental safeguard of mitochondrial remodeling in hepatocytes and indicate compensatory programs with therapeutic relevance for chronic liver disease.

physiology↗

Quantitative Analysis of Meloidogyne incognita Population Density Using Real-Time PCR and Its Correlation with Root-Knot Disease Index in Tabacco (Nicotiana tabacum)

Tobacco root-knot disease represents a significant threat to tobacco production, particularly in the western Henan region, where Meloidogyne incognita is the predominant species. This study collected samples of M. incognita and soil from Luoyang, Henan, and designed specific primers MiF and MiR based on the amplified 735 bp sequence of the ITS1-5.8S-ITS2 region. These primers exhibit mismatches with related species, including M. javanica, M. minor, M. hapla, and M. arenaria, showing 1, 6, 10, and 10 base differences in the forward direction, respectively, 3, 10, and 9 base mismatches in the reverse direction. Although the primers were used to detect corn-wheat soil samples, no amplification was observed. Additionally a real-time quantitative PCR curve for M. incognita in soil was constructed, revealing a negative correlation between the Ct value (Y) and the log-transformed number of nematodes (x) per 20 g of dry soil, represented by the equation y = -0.9757x + 35.565; (R2 = 0.9999, P < 0.01). According to the decomposition efficiency of nematode DNA in soil, the results showed that nematode DNA degrades rapidly in soil, with a degradation rate of approximately 87.3% at 3 days and 99.97% at 14 days. Furthermore, significant differences were observed in the real-time PCR detection efficiency among various nematode forms: the Ct value of J1 was significantly higher than that of J2, while abnormal eggs (empty eggs or internal bubble eggs) exhibited the highest Ct value. The proportion of abnormal eggs in the soil before planting was significantly higher at 64.08% compared to only 15.3% at harvest, indicating that the activity of nematodes in the soil is significantly reduced after harvesting in October and planting in March of the following year. A survey of 126 tobacco plants indicated a significant positive correlation between the root-knot index (RKI) and root-knot nematode density (r = 0.80, p < 0.01). The study identified a minimum disease threshold of 234 individuals / 20 g soil at harvest and revealed a nonlinear relationship between disease severity and nematode density. Specifically, a weak correlation was observed at low density (Low RKI: 0-1; nematode density<2000 individuals/20 g soil, r = 0.49, P<0.05), while a significant correlation was noted at moderate density (High RKI: nematode density>2000 individuals/20 g soil, r = 0.69, P<0.05). This study showed that as the RKI increases, the rate of increase in nematode density in the soil diminishes. These findings provide valuable insights for the development of effective scientific strategies for nematode control.

plant biology↗

The Role of Primate-Specific Genes and Network Dynamics in Cancer Evolution

The atavistic evolutionary theory of cancer evolution highlights the role of ancient and unicell-originated genes, and comprehensive research demonstrated the evolutionary inference. Comparably, very few reports linked young genes with cancer development and maintenance. Here, we found that in cancer cell lines a higher proportion of core essential genes was present among primate-specific genes (PSG) than early metazoan-originated genes (Wilcoxon rank-sum test, p-value = 4.67e-12) and mammal-originated genes (Wilcoxon rank-sum test, p-value = 1.22e-16). Additionally, we found that the loss of many co-expression gene pairs in pan-cancer leads to their network becoming looser compared with normal tissue. However, PSGs particularly those being essential, exhibit a dynamic increase in co-expression, explaining their enhanced role in maintaining cancers. Furthermore, clustering of the gene co-expressions brings a cancer-exclusive module, which contains a large number of PSG connections. We also demonstrate the divergence between essential genes in healthy individuals and those in cancer cells. Our findings complement the atavistic theory in elucidating the evolutionary process of cancer.

evolutionary biology↗

A Novel Approach-Avoidance Task to Study Decision Making Under Outcome Uncertainty

To behave adaptively, people need to integrate information about probabilistic outcomes and balance drives to approach positive outcomes and avoid negative outcomes. However, questions remain about how uncertainty in positive and negative outcomes influence approach-avoid decision-making dynamics. To fill this gap, we developed a novel Probabilistic Approach Avoidance Task (PAAT) and characterized behavior in this task using sequential sampling models In this task, participants (Study 1: blinded mixed clinical sample N=34; Study 2: online nonpsychiatric sample N = 58) made a series of choices between pairs of options, each consisting of variable probabilities of reaching a positive outcome (monetary reward) and of reaching a negative outcome (aversive image). Participants tended to choose options that maximized the likelihood of reward and minimized the likelihood of aversive outcomes. Moreover, the weights they placed on each of these differed for choices where these likelihoods were in opposition (i.e., the riskier option was also more rewarding; incongruent trials) relative to when these were aligned (congruent trials). Computational modeling revealed that the relative influence of rewarding and aversive outcomes on choice was captured by differences in the rate of decision-relevant information accumulation. These modeling results were validated with a series of model comparisons and posterior predictive checks, demonstrating that our sequential sampling models reliably captured our behavioral data. Together, these findings improve our understanding of the influence of motivational conflict, outcome type, and levels of uncertainty on approach-avoid decision-making.

neuroscience↗