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1.
Gut Microbes ; 16(1): 2338946, 2024.
Article in English | MEDLINE | ID: mdl-38656273

ABSTRACT

Synbiotics combine the concepts of probiotics and prebiotics to synergistically enhance the health-associated effects of both components. Previously, we have shown that the intestinal persistence of inulin-utilizing L. plantarum Lp900 is significantly increased in rats fed an inulin-supplemented, high-calcium diet. Here we employed a competitive population dynamics approach to demonstrate that inulin and GOS can selectively enrich L. plantarum strains that utilize these substrates for growth during in vitro cultivation, but that such enrichment did not occur during intestinal transit in rats fed a GOS or inulin-supplemented diet. The intestinal persistence of all L. plantarum strains increased irrespective of their prebiotic utilization phenotype, which was dependent on the calcium level of the diet. Analysis of fecal microbiota and intestinal persistence decline rates indicated that prebiotic utilization capacity did not selectively stimulate intestinal persistence in prebiotic supplemented diets. Moreover, microbiota and organic acid profile analyses indicate that the prebiotic utilizing probiotic strains are vastly outcompeted by the endogenous prebiotic-utilizing microbiota, and that the collective enhanced persistence of all L. plantarum strains is most likely explained by their well-established tolerance to organic acids.


Subject(s)
Feces , Gastrointestinal Microbiome , Inulin , Prebiotics , Animals , Prebiotics/administration & dosage , Inulin/metabolism , Inulin/administration & dosage , Rats , Feces/microbiology , Lactobacillus plantarum/metabolism , Lactobacillus plantarum/physiology , Male , Probiotics/administration & dosage , Synbiotics/administration & dosage , Rats, Sprague-Dawley
2.
Evolution ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38656785

ABSTRACT

Evolutionary theory predicts that accumulation of deleterious mutations in asexually reproducing organisms should lead to genomic decay. Clonally reproducing cell lines, i.e., transmissible cancers, when cells are transmitted as allografts/xenografts, break these rules, and survive for centuries and millennia. The currently known 11 transmissible cancer lineages occur in dogs (Canine Venereal Tumour Disease, CTVT), in Tasmanian devils (Devil Facial Tumour Diseases, DFT 1 and DFT2) and in bivalves (bivalve transmissible neoplasia, BTN). Despite the mutation loads of these cell lines being much higher than observed in human cancers, they have not been eliminated in space and time. Here we provide potential explanations how these fascinating cell lines may have overcome the fitness decline due to the progressive accumulation of deleterious mutations and propose that the high mutation load may carry an indirect positive fitness outcome. We offer ideas on how these host-pathogen systems could be used to answer outstanding questions in evolutionary biology. The recent studies on the evolution of these clonal pathogens reveal key mechanistic insight into transmissible cancer genomes, information that is essential for future studies investigating how these contagious cancer cell lines can repeatedly evade immune recognition, evolve, and survive in the landscape of highly diverse hosts.

3.
ISA Trans ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38664115

ABSTRACT

This paper concerns the bipartite consensus problem of multi-agent systems(MASs) with competitive- cooperative network topology under denial-of-service (DoS) attacks. Firstly, this work extensively analyzes the competitive phenomena that may exist in the information interchange of agents in contrast to the single cooperative behavior between agents. Based on this, some necessary conditions are provided for the system to attain the bipartite consensus. In addition, the event-triggered mechanism (ETM) effectively lowers unnecessary information sharing between agents and eliminates Zeno behavior. Furthermore, the predictive method provides the system with exceptional resistance against common energy-limited DoS attacks and the ability to compensate for information loss caused by DoS attacks. Finally, a numerical simulation proves that the proposed approach is feasible.

4.
Proc Natl Acad Sci U S A ; 121(16): e2314900121, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38588417

ABSTRACT

Microbes grow in a wide variety of environments and must balance growth and stress resistance. Despite the prevalence of such trade-offs, understanding of their role in nonsteady environments is limited. In this study, we introduce a mathematical model of "growth debt," where microbes grow rapidly initially, paying later with slower growth or heightened mortality. We first compare our model to a classical chemostat experiment, validating our proposed dynamics and quantifying Escherichia coli's stress resistance dynamics. Extending the chemostat theory to include serial-dilution cultures, we derive phase diagrams for the persistence of "debtor" microbes. We find that debtors cannot coexist with nondebtors if "payment" is increased mortality but can coexist if it lowers enzyme affinity. Surprisingly, weak noise considerably extends the persistence of resistance elements, pertinent for antibiotic resistance management. Our microbial debt theory, broadly applicable across many environments, bridges the gap between chemostat and serial dilution systems.


Subject(s)
Bacteria , Biochemical Phenomena
5.
Proc Natl Acad Sci U S A ; 121(16): e2318160121, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38598339

ABSTRACT

Organic carbon availability in soil is crucial for shaping microbial communities, yet, uncertainties persist concerning microbial adaptations to carbon levels and the ensuing ecological and evolutionary consequences. We investigated organic carbon metabolism, antibiotic resistance, and virus-host interactions in soils subjected to 40 y of chemical and organic fertilization that led to contrasting carbon availability: carbon-poor and carbon-rich soils, respectively. Carbon-poor soils drove the enrichment of putative genes involved in organic matter decomposition and exhibited specialization in utilizing complex organic compounds, reflecting scramble competition. This specialization confers a competitive advantage of microbial communities in carbon-poor soils but reduces their buffering capacity in terms of organic carbon metabolisms, making them more vulnerable to environmental fluctuations. Additionally, in carbon-poor soils, viral auxiliary metabolic genes linked to organic carbon metabolism increased host competitiveness and environmental adaptability through a strategy akin to "piggyback the winner." Furthermore, putative antibiotic resistance genes, particularly in low-abundance drug categories, were enriched in carbon-poor soils as an evolutionary consequence of chemical warfare (i.e., interference competition). This raises concerns about the potential dissemination of antibiotic resistance from conventional agriculture that relies on chemical-only fertilization. Consequently, carbon starvation resulting from long-term chemical-only fertilization increases microbial adaptations to competition, underscoring the importance of implementing sustainable agricultural practices to mitigate the emergence and spread of antimicrobial resistance and to increase soil carbon storage.


Subject(s)
Carbon , Soil , Soil/chemistry , Carbon/metabolism , Agriculture/methods , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Soil Microbiology
6.
Cell Rep ; 43(4): 114076, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38607917

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3' end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/physiology , SARS-CoV-2/genetics , COVID-19/virology , COVID-19/transmission , Virus Replication , Mutation/genetics , Respiratory Mucosa/virology , Genetic Fitness , Animals , Epithelial Cells/virology , Chlorocebus aethiops , Adaptation, Physiological/genetics , Vero Cells
7.
Elife ; 132024 Apr 19.
Article in English | MEDLINE | ID: mdl-38639482

ABSTRACT

Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (SLITRK2 and FMR1) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked MIR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the MIR-506 family led to reduced male fertility in mice. Despite normal sperm counts, motility, and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked MIR-506 family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the MIR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.


Subject(s)
MicroRNAs , Semen , Male , Animals , Mice , Semen/metabolism , Spermatogenesis/genetics , Spermatozoa/metabolism , Testis/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Mammals/genetics
8.
BMC Ecol Evol ; 24(1): 53, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38658833

ABSTRACT

BACKGROUND: Lizards of the genus Podarcis are widespread in the Mediterranean region, including islands and island archipelagos. These small-bodied lizards have a predominantly protective green-brown colouration. However, some populations display unusual patterns, in which the colouration is predominantly blue or uniformly black. This study explores the factors that influence this chromatic variation, whether environmental (climate and island conditions) or evolutionary (phylogenetic trait conservatism). The colouration of 1400 individuals (27 species) was analysed in the CIELAB colour space. RESULTS: Pagel's λ indicated that colouration is weakly conserved within phylogenetic lineages. Although the island surface plays a key role in the chromatic variability of these lacertids, geographic isolation and climate hold less influence. The colouration of some small island populations tends to be uniform and dark, possibly due to intense intraspecific competition and lower predatory pressure. CONCLUSIONS: This study highlights the importance of island populations in understanding the processes that favour the emergence of extreme phenotypes in small ectothermic vertebrates.


Subject(s)
Lizards , Lizards/physiology , Animals , Mediterranean Region , Color , Pigmentation/physiology , Phylogeny , Islands , Climate , Biological Evolution , Phenotype , Environment
9.
Biomark Res ; 12(1): 41, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38644503

ABSTRACT

Regulatory T cells (Tregs) are essential to the negative regulation of the immune system, as they avoid excessive inflammation and mediate tumor development. The abundance of Tregs in tumor tissues suggests that Tregs may be eliminated or functionally inhibited to stimulate antitumor immunity. However, immunotherapy targeting Tregs has been severely hampered by autoimmune diseases due to the systemic elimination of Tregs. Recently, emerging studies have shown that metabolic regulation can specifically target tumor-infiltrating immune cells, and lipid accumulation in TME is associated with immunosuppression. Nevertheless, how Tregs actively regulate metabolic reprogramming to outcompete effector T cells (Teffs), and how lipid metabolic reprogramming contributes to the immunomodulatory capacity of Tregs have not been fully discussed. This review will discuss the physiological processes by which lipid accumulation confers a metabolic advantage to tumor-infiltrating Tregs (TI-Tregs) and amplifies their immunosuppressive functions. Furthermore, we will provide a summary of the driving effects of various metabolic regulators on the metabolic reprogramming of Tregs. Finally, we propose that targeting the lipid metabolism of TI-Tregs could be efficacious either alone or in conjunction with immune checkpoint therapy.

10.
bioRxiv ; 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38645188

ABSTRACT

Engineered DNA will slow the growth of a host cell if it redirects limiting resources or otherwise interferes with homeostasis. Populations of engineered cells can rapidly become dominated by "escape mutants" that evolve to alleviate this burden by inactivating the intended function. Synthetic biologists working with bacteria rely on genetic parts and devices encoded on plasmids, but the burden of different engineered DNA sequences is rarely characterized. We measured how 301 BioBricks on high-copy plasmids affected the growth rate of Escherichia coli. Of these, 59 (19.6%) negatively impacted growth. The burden imposed by engineered DNA is commonly associated with diverting ribosomes or other gene expression factors away from producing endogenous genes that are essential for cellular replication. In line with this expectation, BioBricks exhibiting burden were more likely to contain highly active constitutive promoters and strong ribosome binding sites. By monitoring how much each BioBrick reduced expression of a chromosomal GFP reporter, we found that the burden of most, but not all, BioBricks could be wholly explained by diversion of gene expression resources. Overall, no BioBricks reduced the growth rate of E. coli by >45%, which agreed with a population genetic model that predicts such plasmids should be "unclonable" because escape mutants will take over during growth of a bacterial colony or small laboratory culture from a transformed cell. We made this model available as an interactive web tool for synthetic biology education and added our burden measurements to the iGEM Registry descriptions of each BioBrick.

11.
Behav Sci (Basel) ; 14(4)2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38667120

ABSTRACT

With the increased emphasis on competition in academic settings, anxiety is becoming more common, which inevitably has some impact on students' learning processes and results. This study aimed to explore how competition-induced anxiety influences students' subjective cognitive load (SCL), attention levels, and test scores. We also investigated the mediating role of the behavioral inhibition system/behavioral activation system (BIS/BAS) in those factors. A total of 101 college students were recruited in Study 1 to learn from five micro-lectures from massive open online courses (MOOCs) under competitive and non-competitive conditions. The results showed that participants' state anxiety (SA) scores were higher after the experiment, participants under the competition condition had higher test scores, and the relationship between SA/ trait anxiety (TA) and SCL could be mediated by the BIS. To obtain more objective data on learning processes (attention levels), we conducted Study 2, which collected behavioral and EEG data from 42 college students during the online learning. The results showed that the competition group had higher SA, lower attention levels, and worse test scores, and the relationship between SA/TA and attention levels could be mediated through the BIS. The present study not only expands previous research by finding that BIS functioning plays an important role in the effects of anxiety on cognitive load and attention but also offers implications for using competitive strategies to motivate students according to their aptitudes.

12.
Cell Rep ; 43(4): 114015, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38568810

ABSTRACT

The type VI secretion system (T6SS), a widespread protein delivery apparatus, plays a role in bacterial competition by delivering toxic effectors into neighboring cells. Identifying new T6SS effectors and deciphering the mechanism that governs their secretion remain major challenges. Here, we report two orphan antibacterial T6SS effectors in the pathogen Pantoea agglomerans (Pa). These effectors share an N-terminal domain, Pantoea type six (PIX), that defines a widespread class of polymorphic T6SS effectors in Enterobacterales. We show that the PIX domain is necessary and sufficient for T6SS-mediated effector secretion and that PIX binds to a specialized Pa VgrG protein outside its C-terminal toxic domain. Our findings underline the importance of identifying and characterizing delivery domains in polymorphic toxin classes as a tool to reveal effectors and shed light on effector delivery mechanisms.


Subject(s)
Bacterial Proteins , Type VI Secretion Systems , Type VI Secretion Systems/metabolism , Bacterial Proteins/metabolism , Protein Domains , Pantoea/metabolism , Protein Binding
13.
Front Psychol ; 15: 1393963, 2024.
Article in English | MEDLINE | ID: mdl-38638508

ABSTRACT

This study aimed to analyze the differences in the precompetitive anxiety and self-confidence according to the side of play, the ranking and the match outcome, under different competitive scenarios, in high level men's padel players from Finland who trained under pressure prior to the competition. 10 men's padel players (28.60 (4.17) years old) from the highest category participated in the research. The CSAI-2R (Competitive State Anxiety Inventory-2 Revised) and STAI-S (State-Trait Anxiety Inventory - State) questionnaires were used and descriptive and inferential analyzes were performed, including Mann-Whitney's U tests. The findings illuminate that, across the player spectrum, somatic anxiety and self-confidence levels are higher before competition compared to training matches. This trend holds true for left-side, higher-ranked and match winning players. Even lower-ranked players exhibit heightened self-confidence preceding competitions. These insights offer valuable considerations for players, coaches, and sports psychologists, fostering a deeper understanding of the intricate interplay between pressure training, competition, and the athlete's psychological landscape.

14.
Ecol Appl ; : e2974, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38646794

ABSTRACT

A wide range of approaches has been used to manage the spread of invasive species, yet invaders continue to be a challenge to control. In some cases, management actions have no effect or may even inadvertently benefit the targeted invader. Here, we use the mid-20th century management of the Red Imported Fire Ant, Solenopsis invicta, in the US as a motivating case study to explore the conditions under which such wasted management effort may occur. Introduced in approximately 1940, the fire ant spread widely through the southeast US and became a problematic pest. Historically, fire ants were managed with broad-spectrum pesticides; unfortunately, these efforts were largely unsuccessful. One hypothesis suggests that, by also killing native ants, mass pesticide application reduced competitive burdens thereby enabling fire ants to invade more quickly than they would in the absence of management. We use a mechanistic competition model to demonstrate the landscape-level effects of such management. We explicitly model the extent and location of pesticide applications, showing that the same pesticide application can have a positive, neutral, or negative effect on the progress of an invasion, depending on where it is applied on the landscape with respect to the invasion front. When designing management, the target species is often considered alone; however, this work suggests that leveraging existing biotic interactions, specifically competition with native species, can increase the efficacy of management. Our model not only highlights the potential unintended consequences of ignoring biotic interactions, but also provides a framework for developing spatially explicit management strategies that take advantage of these biotic interactions to work smarter, not harder.

15.
Food Chem ; 448: 139021, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38574711

ABSTRACT

The widespread use of glyphosate (Gly) poses significant risks to environmental and human health, underscoring the urgent need for its sensitive and rapid detection. In this work, we innovated by developing a novel material, ionic liquids, which formed the ionic probe "[P66614]2[2,3-DHN]-Cu2+ (PDHN-Cu2+)" through coordination with Cu2+. This probe capitalized on the distinctive fluorescence quenching properties of ionic liquids in the presence of Cu2+, driven by synergistic interactions between anions and cations. Glyphosate disrupted the PDHN-Cu2+ coordination structure due to its stronger affinity for Cu2+, triggering a "turn-on" fluorescence response. Impressively, PDHN-Cu2+ enabled the sensitive detection of glyphosate within just one minute, achieving a detection limit as low as 71.4 nM and excellent recovery rates of 97-103% in diverse samples. This groundbreaking approach, utilizing ionic probes, lays a robust foundation for the accurate and real-time monitoring of pesticides, employing a strategy based on synergism and competitive coordination.

16.
Curr Opin Psychol ; 57: 101814, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38626690

ABSTRACT

In this work, we propose that humor violates norms that can build consensus or escalate conflict in negotiations. Drawing on social identity theory, we propose that humor commits norm violations that are more likely to be perceived as benign among ingroup observers in negotiations, but perceived as offensive to outgroup observers in negotiations. We introduce the Comedy, Consensus, and Conflict Framework to shed light on the interpersonal effect of humor on negotiations. When humor is expressed to an ingroup observer, relative to neutral communication, humor is more likely to violate weak norms that govern social group membership resulting in the violation as being perceived as benign, which promotes cooperative behaviors in negotiations such as concessions and collaborative problem-solving. By contrast, when humor is expressed to an outgroup observer, relative to neutral communication, humor is more likely to violate strong norms that define social group membership resulting in the violation as being interpreted as offensive, which triggers competitive behaviors in negotiations such as aggressive offers and hardened positions. Furthermore, we suggest that humor not only generates appraisals of social identity threats, but also affective responses that influence negotiation behavior. Finally, we expand our theoretical model about humor to consider key relational factors that influence norm strength, which motivates whether negotiators appraise norm violations as offensive or benign.

17.
Int J Sports Physiol Perform ; : 1-8, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38626892

ABSTRACT

PURPOSE: This study aimed to investigate the peak performance characteristics of the world top-8 swimmers and the key factors involved in the journey toward achieving better peak performance. METHODS: The results of the world top-8 swimmers from 2001 to 2022 were collected from the World Aquatics performance database. Progression to peak performance was tracked with individual quadratic trajectories (1191 cases). Utilizing k-means clustering to group competitive feature variables, this study investigated key developmental factors through a binary logistic regression model, using the odds ratio (OR) to represent whether a factor was favorable (OR > 1) or unfavorable (OR < 1). RESULTS: Significant differences (P < .001) in the peak age between men (23.54/3.80) and women (22.31/4.60) were noticed, while no significant differences (P > .05) in the peak-performance window for both sexes appeared. Peak performance occurred at later ages for the sprint for both sexes, and women had a longer duration in peak-performance window for sprint (P < .05). Peak-performance occurred at later ages for the breaststroke and butterfly for both sexes (P < .05). Binary logistic regression revealed that high first-participation performance (OR = 1.502), high major-competition performance (OR = 4.165), early first-major-competition age (OR = 1.441), participation frequency above 4 times/year in both phase 2 (4.3-8.0 times/y, OR = 3.940; 8.1-20.0 times/y, OR = 5.122) and phase 3 (4.1-7.5 times/y: OR = 5.548; 7.7-15.0 times/y: OR = 7.526), and a career length of 10 years or more (10-15 y, OR = 2.102; 16-31 y, OR = 3.480) were favorable factors for achieving better peak performance. CONCLUSIONS: Peak performance characteristics varied across sex, swimming stroke, and race distance in the world top-8 swimmers. Meanwhile, the research indicated that certain specific developmental factors were key conditions for the world top-8 swimmers to achieve better peak performance in the future.

18.
Pers Soc Psychol Bull ; : 1461672241242182, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38629766

ABSTRACT

This research investigated how an instance of intergroup helping affects intergroup attitudes and cooperative behavior. Past research demonstrates that helping behavior elicits prosociality, both reciprocally and toward uninvolved third parties. However, much of this research has either ignored group membership altogether or has assumed a shared group identity between benefactor and beneficiary. Where intergroup helping has been directly evaluated, more negative intergroup attitudes are often observed. The current study examined the effects of an instance of intergroup helping, introduced during a card game, on the beneficiary's attitudes of closeness and cooperative trading behavior as well as those of ingroup and outgroup witnesses to the helping act. Results from this well-powered study (N = 1,249) indicate that although intergroup helping is less likely to impact feelings of closeness, intergroup cooperative trading increases for both the beneficiary and the intergroup observers. These findings add to the understanding of how helping impacts intergroup relations.

19.
Angew Chem Int Ed Engl ; : e202405428, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563631

ABSTRACT

The extensively studied Prussian blue analogs (PBAs) in various batteries are limited by their low discharge capacity, or subpar rate etc., which are solely reliant on the cation (de)intercalation mechanism. In contrast to the currently predominant focus on cations, we report the overlooked anion-cation competition chemistry (Cl-, K+, Zn2+) stimulated by high-voltage scanning. With our designed anion-cation combinations, the KFeMnHCF cathode battery delivers comprehensively superior discharge performance, including voltage plateau >2.0 V (vs. Zn/Zn2+), capacity >150 mAh g-1, rate capability with capacity maintenance above 96 % from 0.6 to 5 A g-1, and cyclic stability exceeding 3000 cycles. We further verify that such comprehensive improvement of electrochemical performance utilizing anion-cation competition chemistry is universal for different types of PBAs. Our work would pave a new and efficient road towards the next-generation high-performance PBAs cathode batteries.

20.
Cancer Lett ; 589: 216831, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38574882

ABSTRACT

How tumors arise or the cause of precancerous lesions is a fundamental question in cancer biology. It is generally accepted that tumors originate from normal cells that undergo uncontrolled proliferation owing to genetic alterations. At the onset of adenoma formation, cancer driver mutations confer clonal growth advantage, enabling mutant cells to outcompete and eliminate the surrounding healthy cells. Hence, the development of precancerous lesions is not only attributed to the expansion of pre-malignant clones, but also relies on the relative fitness of mutated cells compared to the neighboring cells. Colorectal cancer (CRC) is an excellent model to investigate cancer origin as it follows a stereotypical process from mutant cell hyperplasia to adenoma formation and progression. Here, we review the evolving understanding of colonic tumor development, focusing on how cell intrinsic and extrinsic factors impact cell competition and the "clone war" between cancer-initiating cells and normal stem cells. We also discuss the promises and limitations of targeting cell competitiveness in cancer prevention and early intervention. The field of tumor initiation is currently in its infancy, elucidating the adenoma origin is crucial for designing effective prevention strategies and early treatments before cancer becomes incurable.


Subject(s)
Adenoma , Colonic Neoplasms , Colorectal Neoplasms , Precancerous Conditions , Humans , Precancerous Conditions/genetics , Mutation , Adenoma/genetics , Adenoma/prevention & control , Adenoma/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/prevention & control , Colorectal Neoplasms/pathology
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