Phenotypic Plasticity Research Articles

Wave exposure influences kelp morphological and biomechanical phenotypic plasticity

Despite global and local declines in kelp ecosystems, luxuriant kelp beds persist at the Eastern Shore Islands (ESI) in Nova Scotia, Canada. Kelp beds in other regions of Nova Scotia were defoliated as the invasive bryozoan Membranipora membranacea and warming temperatures weakened kelp tissues and enhanced erosion and dislodgment. We propose that the high wave exposure at the ESI causes morphological and biomechanical phenotypic plasticity of kelp tissues. We compared differences in morphology and mechanical properties of the kelps Laminaria digitata and Saccharina latissima across 3 sites with different wave exposures, and differences in mechanical properties across blade lengths. Both species showed morphological plasticity; higher wave exposure resulted in longer and thicker stipes and thicker blades with increased branching. The mechanical properties of L. digitata showed increased breaking stress (strength) and strain (extensibility) with higher wave exposure, whereas S. latissima did not show mechanical plasticity with increasing exposure. For both species, blades were weaker but more extensible at the meristem and stronger but less extensible near the distal end of the blade. Larger and stronger kelp from high-exposure areas may promote the persistence of kelp beds in the ESI despite local stressors.

Growth Patterns of Small Pelagic Fish in West Africa

Small pelagic fishes play important ecological roles in marine ecosystems, constitute some of the most economically valuable fisheries resources, and play a vital role in West African food security. Often living in upwelling regions, these species appear to have developed mechanisms to cope with environmental variability, such as opportunistic reproductive tactics, enhancing their growth performance, or increasing their egg production by following the more predictable system attributes of seasonal cycles. To test this hypothesis, we investigated size-dependent patterns of the two growth mechanisms (i.e., growth rate) of two West African small pelagic populations (Ethmalosa fimbriata and Sardinella maderensis) in upwelling environments. These results were discussed with other areas in African tropical Atlantic waters. The monthly mean length of both species showed a large variation over the study period. Based on the fish length-frequency data and a coastal upwelling index, we found that the growth peaks of the species tended to occur during the most intense periods of upwelling (March–April). This study showed a significant decrease in size compared with other species found in other regions. It demonstrates how the geographical distribution of the same species, together with location-specific variation in temperature and food, can combine to determine local and regional growth responses in pelagic fish. Changes in growth rate may be an adaptive tactic in response to environmental change, as well as phenotypic plasticity in fish. This knowledge is essential to predict future changes in fish productivity and distribution vs. climate and to provide effective advice for ecosystem-based management.

Local adaptation and phenotypic plasticity drive leaf trait variation in the California endemic toyon (Heteromeles arbutifolia).

To survive climate change and habitat loss, plants must rely on phenotypic changes in response to the environment, local adaptation, or migration. Understanding the drivers of intraspecific variation is critical to anticipate how plant species will respond to climate change and to inform conservation decisions. Here we explored the extent of local adaptation and phenotypic plasticity in Heteromeles arbutifolia, toyon, a species endemic to the California Floristic Province. We collected leaves from 286 individuals across toyon's range and used seeds from 37 individuals to establish experimental gardens in the northern and southern parts of toyon's range. We measured leaf functional traits of the wild-collected leaves and functional and fitness traits of the offspring grown in the experimental gardens. We then investigated the relationships between traits and source environment. Most traits we investigated responded plastically to the environment, and some traits in young seedlings were influenced by maternal effects. We found strong evidence that variation in leaf margins is a result of local adaptation to variation in temperature and temperature range. However, the source environment was not related to fitness traits or survival in the experimental gardens. Our findings reiterate the adaptive role of toothed leaf margins in colder and more seasonally variable environments. Additionally, we provide evidence that fitness of toyon is not dependent on where they are sourced, and thus toyon can be sourced across its range for restoration purposes.

Arrested development and increased incidence of sandprawn embryonic aberrations along an intertidal human recreation gradient.

Anthropogenic pressures are increasing in coastal ecosystems globally, yet identifying robust indicators of change and managing coastal resources can be complicated by phenotypic plasticity and differential life-history responses of key organisms. We illustrate this using biogeochemical and sandprawn (Kraussillichirus kraussi) response metrics along a human recreation gradient (trampling, sandprawn harvesting) in a South African lagoonal ecosystem. Benthic compaction, oxygen depletion and high porewater ammonia concentrations were associated with greatest recreation intensity. Sandprawn abundance was similar across the recreation gradient and body condition was counter-intuitively greater in areas with maximum recreation, but with higher frequencies of embryonic aberrations and arrested development. These findings suggest different vulnerabilities of life-history stages of sandprawns to recreation, with embryonic stages being highly susceptible. We suggest that embryonic aberrations and developmental changes in endobenthic crustaceans may be sensitive bioindicators of recreation-induced changes in sedimentary systems.

Influence of captive breeding environment on the locomotor performance and metabolism of the threatened Alcatraz Snouted Treefrog, Ololygon alcatraz

AbstractEx situ conservation is a complementary strategy to in situ efforts and is vital for safeguarding endangered species through maintenance and breeding in captivity with potential for reintroductions into natural environments. However, it is crucial to recognize that prolonged captivity can lead to diminished abilities of organisms over generations. Factors linked to the impact of phenotypic plasticity during development, such as restricted movement, may affect organism performance during ex situ conservation efforts, potentially making reintroduction into the wild unfeasible. Consequently, it is imperative to analyze physiological differences between captive‐bred and wild individuals. Therefore, this study investigates how captivity influences locomotor performance, morphology, and metabolic capacities of adults and juveniles of the threatened treefrog Ololygon alcatraz, in comparison to natural populations. We obtained proportional measurements of individuals and assessed their locomotor performance through jumping exercise. We also measured the metabolic capacities of the frogs by examining the activity of enzymes involved in energetic metabolic pathways in their skeletal muscle fibers. We found that wild adult frogs had larger limbs, greater jumping abilities, and a more glycolytic profile, while captive adult frogs had smaller limbs and increased aerobic enzyme activity compared to their wild counterparts. These differences probably arise from phenotypic plasticity in ontogenetic development that differs between captive and natural environments, as juveniles do not show such differences. These results highlight the need for innovative strategies in managing captive O. alcatraz populations, which will aid in their successful translocation to the wild and strengthen ex situ conservation efforts.

Hyperspectral Leaf Reflectance Detects Interactive Genetic and Environmental Effects on Tree Phenotypes, Enabling Large-Scale Monitoring and Restoration Planning Under Climate Change.

Plants respond to rapid environmental change in ways that depend on both their genetic identity and their phenotypic plasticity, impacting their survival as well as associated ecosystems. However, genetic and environmental effects on phenotype are difficult to quantify across large spatial scales and through time. Leaf hyperspectral reflectance offers a potentially robust approach to map these effects from local to landscape levels. Using a handheld field spectrometer, we analyzed leaf-level hyperspectral reflectance of the foundation tree species Populus fremontii in wild populations and in three 6-year-old experimental common gardens spanning a steep climatic gradient. First, we show that genetic variation among populations and among clonal genotypes is detectable with leaf spectra, using both multivariate and univariate approaches. Spectra predicted population identity with 100% accuracy among trees in the wild, 87%-98% accuracy within a common garden, and 86% accuracy across different environments. Multiple spectral indices of plant health had significant heritability, with genotype accounting for 10%-23% of spectral variation within populations and 14%-48% of the variation across all populations. Second, we found gene by environment interactions leading to population-specific shifts in the spectral phenotype across common garden environments. Spectral indices indicate that genetically divergent populations made unique adjustments to their chlorophyll and water content in response to the same environmental stresses, so that detecting genetic identity is critical to predicting tree response to change. Third, spectral indicators of greenness and photosynthetic efficiency decreased when populations were transferred to growing environments with higher mean annual maximum temperatures relative to home conditions. This result suggests altered physiological strategies further from the conditions to which plants are locally adapted. Transfers to cooler environments had fewer negative effects, demonstrating that plant spectra show directionality in plant performance adjustments. Thus, leaf reflectance data can detect both local adaptation and plastic shifts in plant physiology, informing strategic restoration and conservation decisions by enabling high resolution tracking of genetic and phenotypic changes in response to climate change.

Deciphering normal and cancer stem cell niches by spatial transcriptomics: opportunities and challenges.

Cancer stem cells (CSCs) often exhibit stem-like attributes that depend on an intricate stemness-promoting cellular ecosystem within their niche. The interplay between CSCs and their niche has been implicated in tumor heterogeneity and therapeutic resistance. Normal stem cells (NSCs) and CSCs share stemness features and common microenvironmental components, displaying significant phenotypic and functional plasticity. Investigating these properties across diverse organs during normal development and tumorigenesis is of paramount research interest and translational potential. Advancements in next-generation sequencing (NGS), single-cell transcriptomics, and spatial transcriptomics have ushered in a new era in cancer research, providing high-resolution and comprehensive molecular maps of diseased tissues. Various spatial technologies, with their unique ability to measure the location and molecular profile of a cell within tissue, have enabled studies on intratumoral architecture and cellular cross-talk within the specific niches. Moreover, delineation of spatial patterns for niche-specific properties such as hypoxia, glucose deprivation, and other microenvironmental remodeling are revealed through multilevel spatial sequencing. This tremendous progress in technology has also been paired with the advent of computational tools to mitigate technology-specific bottlenecks. Here we discuss how different spatial technologies are used to identify NSCs and CSCs, as well as their associated niches. Additionally, by exploring related public data sets, we review the current challenges in characterizing such niches, which are often hindered by technological limitations, and the computational solutions used to address them.

Immune defense adaptation of Strauchbufo raddei population in heavy metal polluted area: Insights from developmental and environmental perspectives

The adjustment of immune defense mechanisms is a crucial aspect of biological adaptation to stressful environments. Amphibians, with their unique metamorphic process, experience distinct life stages and exhibit diverse immune defense components. While previous studies have focused on specific immune changes during particular life stages under stress, this research addresses a critical gap by exploring the adaptive immune defense strategies of Strauchbufo raddei in heavy metal-polluted environments. We conducted laboratory experiments, exposing offspring from both polluted and unpolluted areas to control and heavy metal treatments, while continuously monitoring changes in immune components during key metamorphic stages. Notably, we examined the role of the skin microbiome, a crucial but often overlooked barrier against pathogens. The results indicated that individuals from polluted areas exhibited some tolerance to heavy metal exposure, though overall immune function remained diminished. During metamorphosis, when immune defenses are most vulnerable, the skin microbiome rapidly enriched beneficial bacteria, preventing pathogenic colonization and playing a pivotal role in maintaining immune defense in contaminated environments. Moreover, our research highlights energy allocation strategies involving corticosterone and body fat content, enabling populations to maintain development despite immune compromise. The immune adaptations observed may be fixed through genetic assimilation, suggesting a rapid evolutionary response to environmental stress. However, this reduces phenotypic plasticity, making populations more vulnerable to future environmental changes. This study provides key insights into the survival strategies of amphibian populations in heavy metal-contaminated areas, laying the foundation for future research on molecular and evolutionary adaptations.

Expression of CD68 and CD163 in malignant epithelial cells of oral squamous cell carcinoma: phenotypic shift or mere cell fusion

Background / purposeThe progression of epithelial to mesenchymal tissue (EMT) is a highly intricate process that facilitates the transformation of cancer cells, allowing them to changeover their characteristic epithelial properties to mesenchymal attributes. This notable change empowers the cells with enhanced mobility and the ability to migrate to distant locations. Furthermore, it is imperative to adopt the idea of macrophage tumor cell fusion to achieve comprehensive considerate of this phenomenon. Our primary objective was to conduct a thorough investigation of macrophage-restricted antigens expression, specifically CD68 and CD163, in malignant epithelial cells of oral cavity squamous cell carcinoma (OSCC) to elucidate aforementioned perceptions. Materials and methodsCD68 and CD163 immunohistochemical expression were assessed in oral squamous cell carcinoma (OSCC), encompassing both the neoplastic cells and the tumor-associated macrophages (TAMs). ResultsBoth CD68 and CD163 antigens were revealed in OSCC malignant epithelial cells in a granular cell pattern, localized in membrane and cytoplasm of tumor cells respectively as well as in the infiltrating TAMs. ConclusionThe macrophage antigens were not limited to the infiltrating tumor-associated macrophages (TAMs), but were also observed in a substantial proportion of OSCC malignant epithelial cells within the tumor parenchyma. This particular expression pattern may represent a subset of tumor cells that have undergone an epithelial to a mesenchymal phenotypic transition. In addition, fusion of macrophages with tumor cells cannot be excluded; both might be associated with increased metastatic activity of OSCC.

Genome-Wide Association Study of Sweet Potato Storage Root Traits Using GWASpoly, a Gene Dosage-Sensitive Model

Sweet potato (Ipomoea batatas) is an important food crop that plays a pivotal role in preserving worldwide food security. Due to its polyploid genome, high heterogeneity, and phenotypic plasticity, sweet potato genetic characterization and breeding is challenging. Genome-wide association studies (GWASs) can provide important resources for breeders to improve breeding efficiency and effectiveness. GWASpoly was used to identify 28 single nucleotide polymorphisms (SNPs), comprising 21 unique genetic loci, associated with sweet potato storage root traits including dry matter (4 loci), subjective flesh color (5 loci), flesh hue angle (3 loci), and subjective skin color and skin hue angle (9 loci), in 384 accessions from the USDA sweet potato germplasm collection. The I. batatas ‘Beauregard’ and I. trifida reference genomes were utilized to identify candidate genes located within 100 kb from the SNPs that may affect the storage traits of dry matter, flesh color, and skin color. These candidate genes include transcription factors (especially Myb, bHLH, and WRKY family members), metabolite transporters, and metabolic enzymes and associated proteins involved in starch, carotenoid, and anthocyanin synthesis. A greater understanding of the genetic loci underlying sweet potato storage root traits will enable marker-assisted breeding of new varieties with desired traits. This study not only reinforces previous research findings on genes associated with dry matter and β-carotene content but also introduces novel genetic loci linked to these traits as well as other root characteristics.

E2F1-induced autocrine IL-6 inflammatory loop mediates cancer-immune crosstalk that predicts T cell phenotype switching and therapeutic responsiveness

Melanoma is a metastatic, drug-refractory cancer with the ability to evade immunosurveillance. Cancer immune evasion involves interaction between tumor intrinsic properties and the microenvironment. The transcription factor E2F1 is a key driver of tumor evolution and metastasis. To explore E2F1’s role in immune regulation in presence of aggressive melanoma cells, we established a coculture system and utilized transcriptome and cytokine arrays combined with bioinformatics and structural modeling. We identified an E2F1-dependent gene regulatory network with IL6 as a central hub. E2F1-induced IL-6 secretion unleashes an autocrine inflammatory feedback loop driving invasiveness and epithelial-to-mesenchymal transition. IL-6-activated STAT3 physically interacts with E2F1 and cooperatively enhances IL-6 expression by binding to an E2F1-STAT3-responsive promoter element. The E2F1-STAT3/IL-6 axis strongly modulates the immune niche and generates a crosstalk with CD4+ cells resulting in transcriptional changes of immunoregulatory genes in melanoma and immune cells that is indicative of an inflammatory and immunosuppressive environment. Clinical data from TCGA demonstrated that elevated E2F1, STAT3, and IL-6 correlate with infiltration of Th2, while simultaneously blocking Th1 in primary and metastatic melanomas. Strikingly, E2F1 depletion reduces the secretion of typical type-2 cytokines thereby launching a Th2-to-Th1 phenotype shift towards an antitumor immune response. The impact of activated E2F1-STAT3/IL-6 axis on melanoma-immune cell communication and its prognostic/therapeutic value was validated by mathematical modeling. This study addresses important molecular aspects of the tumor-associated microenvironment in modulating immune responses, and will contribute significantly to the improvement of future cancer therapies.

Elevated expression levels of the protein kinase DYRK1B induce mesenchymal features in A549 lung cancer cells

BackgroundThe protein kinase DYRK1B is a negative regulator of cell proliferation but has been found to be overexpressed in diverse human solid cancers. While DYRK1B is recognized to promote cell survival and adaption to stressful conditions, the consequences of elevated DYRK1B levels in cancer cells are largely uncharted.MethodsTo elucidate the role of DYRK1B in cancer cells, we established a A549 lung adenocarcinoma cell model featuring conditional overexpression of DYRK1B. This system was used to characterize the impact of heightened DYRK1B levels on gene expression and to monitor phenotypic and functional changes.ResultsA549 cells with induced overexpression of wild type DYRK1B acquired a mesenchymal cell morphology with diminished cell-cell contacts and a reorganization of the pericellular actin cytoskeleton into stress fibers. This transition was not observed in cells overexpressing a catalytically impaired DYRK1B variant. The phenotypic changes were associated with increased expression of the transcription factors SNAIL and SLUG, which are core regulators of epithelial mesenchymal transition (EMT). Further profiling of DYRK1B-overexpressing cells revealed transcriptional changes that are characteristic for the mesenchymal conversion of epithelial cells, including the upregulation of genes that are related to cancer cell invasion and metastasis. Functionally, DYRK1B overexpression enhanced the migratory capacity of A549 cells in a wound healing assay.ConclusionsThe present data identify DYRK1B as a regulator of phenotypic plasticity in A549 cells. Increased expression of DYRK1B induces mesenchymal traits in A549 lung adenocarcinoma cells.

Progressive plasticity during colorectal cancer metastasis.

As cancers progress, they become increasingly aggressive-metastatic tumours are less responsive to first-line therapies than primary tumours, they acquire resistance to successive therapies and eventually cause death1,2. Mutations are largely conserved between primary and metastatic tumours from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression and therapy resistance3-5. However, we lack an understanding of metastatic cell states and the mechanisms by which they transition. Here, in a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that, although primary tumours largely adopt LGR5+ intestinal stem-like states, metastases display progressive plasticity. Cancer cells lose intestinal cell identities and reprogram into a highly conserved fetal progenitor state before undergoing non-canonical differentiation into divergent squamous and neuroendocrine-like states, a process that is exacerbated in metastasis and bychemotherapy and is associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues compared with their intestinal lineage-restricted primary tumour counterparts. We identify PROX1 as a repressor of non-intestinal lineage in the fetal progenitor state, and show thatdownregulation of PROX1 licenses non-canonical reprogramming.

The Adaptive Mechanism of Ginseng Rhizomes in Response to Habitat Changes

Panax ginseng, a perennial medicinal plant, utilizes its dried roots and rhizomes for medicinal purposes. Currently, in China, ginseng cultivation employs two methods: under-forest and farmland planting. These methods create distinct habitats, significantly influencing the ginseng’s rhizome morphology and, consequently, its economic value. In this study, two-year-old ginsengs were transplanted into farmland (TCG), a larch forest (TLCG) and a Quercus mongolica forest (TQCG) to analyze the differences in rhizome phenotypes caused by habitat changes. The results showed that there were significant differences in light intensity and the soil’s available phosphorus and potassium contents between farmland and forest environments. The differences in habitats led to different adaptability of the ginseng’s rhizome morphology. Compared with TCG, the rhizomes of TLCG and TQCG were significantly elongated by 48.36% and 67.34%, respectively. After the rhizomes’ elongation in TLCG and TQCG, there was an increase in indole-3-acetic acid (IAA) contents and a decrease in lignin contents. By analyzing the expression of key genes, we found that, compared with TCG, the expression of key enzymes of lignin biosynthesis genes such as PgCOMT and PgCCR4 were down-regulated. The difference in ginseng’s rhizome length is related to the signal transduction pathway of auxin and gibberellin. In addition, we preliminarily screened out transcription factors PgWRKY75, PgDIV, and PgbHLH93.1, which can actively respond to habitat changes and play important roles in the elongation of ginseng rhizomes. In summary, this study elucidates the phenotypic plasticity strategy of ginseng rhizomes in response to habitat changes and delineates the regulatory mechanism behind phenotypic adaptation, offering novel insights into ginseng’s morphogenesis.

Plant responses to urban gradients: Extinction, plasticity, adaptation

Abstract Biodiversity‐oriented urban management and planning require information on the drivers of wildlife composition and ecosystem function within cities. Urban landscapes impose environmental gradients along which species may be filtered away, or respond by showing adaptive variation in functional trait values. Such trait variation may in turn be due to a species' phenotypic plasticity, or a consequence of microevolution leading to local adaptation. This study investigates three possible plant responses to urban environmental gradients, with different evolutionary consequences: extinction, plasticity and adaptation. We assessed whether individual functional traits (LMA—leaf mass per area, plant height and flower length), population performance traits (seed mass and germination rate), as well as species frequency in the plant community, responded to gradients in mowing frequency, soil fertility and structure, temperature and surrounding mean building height, among four herbaceous plant species present in the metropolitan area of Strasbourg. Using a common garden experiment, we tested whether the observed trait variation was hereditary, and may thus constitute evidence for local adaptation. Our results detected the three types of expected responses. Plantago lanceolata is plastic to urban gradients, and Trifolium pratense showed both plastic and hereditary responses. Dactylis glomerata and Medicago lupulina showed all three responses: they both declined under increasing mowing frequency, were plastic to surrounding mean building height, and showed hereditary responses to different urban gradients. Urban management and planning therefore impact on the evolutionary capabilities of plants in cities. In the case of management this is highlighted by the detected trends in species' traits and frequency in response to mowing. The consequences of urban planning are evidenced by mean building height eliciting most often plastic and adaptive responses. Synthesis. Herbaceous plants often change their morphology in response to urban conditions: grass cutting, altered soils, warmer temperatures and being surrounded by tightly packed buildings. These changes are sometimes hereditary, which suggests that city management and planning affect the ability of plants to survive and evolve in urban environments.

Alternations in inflammatory macrophage niche drive phenotypic and functional plasticity of Kupffer cells

Inflammatory signals lead to recruitment of circulating monocytes and induce their differentiation into pro-inflammatory macrophages. Therefore, whether blocking inflammatory monocytes can mitigate disease progression is being actively evaluated. Here, we employ multiple lineage-tracing models and show that monocyte-derived macrophages (mo-mac) are the major population of immunosuppressive, liver metastasis-associated macrophages (LMAM), while the proportion of Kupffer cells (KC) as liver-resident macrophages is diminished in metastatic nodules. Paradoxically, genetic ablation of mo-macs results in only a marginal decrease in LMAMs. Using a proliferation-recording system and a KC-tracing model in a monocyte-deficient background, we find that LMAMs can be replenished either via increased local macrophage proliferation or by promoting KC infiltration. In the latter regard, KCs undergo transient proliferation and exhibit substantial phenotypic and functional alterations through epigenetic reprogramming following the vacating of macrophage niches by monocyte depletion. Our data thus suggest that a simultaneous blockade of monocyte recruitment and macrophage proliferation may effectively target immunosuppressive myelopoiesis and reprogram the microenvironment towards an immunostimulatory state.

Expression of seed hydration memory through phenotypic plasticity of Senna spectabilis var. excelsa seedlings under water deficit

Expression of seed hydration memory through phenotypic plasticity of Senna spectabilis var. excelsa seedlings under water deficit

Comparative Analysis of Some Morpho-cultural Characters of Venturia inaequalis (Apple Scab Pathogen) under Kashmir Conditions

Apple (Malus × domestica Borkh.) represents one of the most widely cultivated and economically important temperate fruit crops in the world. However, its cultivation faces significant challenges due to various fungal pathogens, particularly apple scab inflicted by Venturia inaequalis, which has a profound impact on the yield and quality of apple, resulting in substantial economic loss. The pervasive nature of V. inaequalis and its ability to damage crops poses a serious threat to sustainable apple production. In this study, the morpho-cultural characteristics of V. inaequalis were systematically analyzed and compared between the Shopian and Baramullah districts of the Kashmir Valley. Ten isolates from each district were grown on Malt Extract Agar (MEA) and Potato Dextrose Agar (PDA) for comparative analysis. The colonies were characterized by a compact hue ranging from greyish-green to blackish and exhibited a densely velvety texture. Mycelial growth was predominantly aerial, with some isolates displaying partial irregularity in colony margins, while others exhibited greater uniformity. The mean colony radii for potato dextrose agar and malt extract agar media was measured as 23.01 mm and 28.50 mm for the Shopian district, and 28.09 mm and 33.33 mm for the Baramullah district, respectively. The mean conidial spore density was recorded at 27.87 spores/cm² for the Baramullah district and 34.67 spores/cm² for the district Shopian, respectively. This variation could be attributed to several factors, including genetic diversity within the pathogen populations, differences in altitude, climate, and other environmental factors, the selection pressure exerted by fungicide applications, the emergence of novel pathogen races, and phenotypic plasticity driven by the differing agricultural practices and microclimatic conditions in the respective regions.

AKT and the Hallmarks of Cancer.

Nearly a quarter century ago, Hanahan and Weinberg conceived six unifying principles explaining how normal cells transform into malignant tumors. Their provisional set of biological capabilities acquired during tumor development  cancer hallmarks  would evolve to fourteen tenets as knowledge of cancer genomes, molecular mechanisms, and the tumor microenvironment expanded, most recently adding four emerging enabling characteristics: phenotypic plasticity, epigenetic reprogramming, polymorphic microbiomes, and senescent cells. AKT kinases are critical signaling molecules that regulate cellular physiology upon receptor tyrosine kinases and phosphatidylinositol 3-kinase activation. The complex branching of the AKT signaling network involves several critical downstream nodes that significantly magnify its functional impact, such that nearly every organ system and cell in the body may be affected by AKT activity. Conversely, tumor intrinsic dysregulation of AKT can have numerous adverse cellular and pathological ramifications, particularly in oncogenesis, as multiple tumor suppressors and oncogenic proteins regulate AKT signaling. Herein, we review the mounting evidence implicating the AKT pathway in the aggregate of currently recognized hallmarks of cancer underlying the complexities of human malignant diseases. The challenges, recent successes, and likely areas for exciting future advances in targeting this complex pathway are also discussed.

Synergistic phenotypic adaptations of motile purple sulphur bacteria Chromatium okenii during lake-to-laboratory domestication.

Isolating microorganisms from natural environments for cultivation under optimized laboratory settings has markedly improved our understanding of microbial ecology. Artificial growth conditions often diverge from those in natural ecosystems, forcing wild isolates into distinct selective pressures, resulting in diverse eco-physiological adaptations mediated by modification of key phenotypic traits. For motile microorganisms we still lack a biophysical understanding of the relevant traits emerging during domestication and their mechanistic interplay driving short-to-long-term microbial adaptation under laboratory conditions. Using microfluidics, atomic force microscopy, quantitative imaging, and mathematical modeling, we study phenotypic adaptation of Chromatium okenii, a motile phototrophic purple sulfur bacterium from meromictic Lake Cadagno, grown under laboratory conditions over multiple generations. Our results indicate that naturally planktonic C. okenii leverage shifts in cell-surface adhesive interactions, synergistically with changes in cell morphology, mass density, and distribution of intracellular sulfur globules, to suppress their swimming traits, ultimately switching to a sessile lifeform. A computational model of cell mechanics confirms the role of such phenotypic shifts in suppressing the planktonic lifeform. By investigating key phenotypic traits across different physiological stages of lab-grown C. okenii, we uncover a progressive loss of motility during the early stages of domestication, followed by concomitant deflagellation and enhanced surface attachment, ultimately driving the transition of motile sulfur bacteria to a sessile state. Our results establish a mechanistic link between suppression of motility and surface attachment via phenotypic changes, underscoring the emergence of adaptive fitness under laboratory conditions at the expense of traits tailored for natural environments.