Invasive Potential Research Articles

Nuclear localization of APLF facilitates breast cancer metastasis

Most breast cancer deaths result from metastases. We previously reported that DNA repair factor and histone chaperone Aprataxin PNK-like Factor (APLF) is involved in EMT-associated metastasis of triple negative breast cancer (TNBC) cells. However, non-metastatic cells also expressed APLF, the implications of which in disease advancement remain uncertain. Here, we demonstrate that the metastatic prognosis of breast cancer cells may be determined by the cellular localization of APLF. Using TNBC patient samples and cell lines, we discovered that APLF was localized in the nucleus and cytoplasm, whereas other subtypes of breast cancer had cytosolic or perinuclear localization. To investigate metastatic properties in vitro and in vivo, we modeled APLF differential localization by stably producing APLF-tagged nuclear localization signal (NLS) in the luminal subtype MCF7 cells in the absence of putative APLF NLS. Nuclear APLF in non-metastatic MCF7 cells demonstrated pronounced migration, invasion and metastatic potential. We obtained the mechanistic insight from molecular studies that PARP1 could facilitate the transport of APLF from the cytosol to the nucleus, assisting in the metastasis of TNBC cells linked with EMT. Inhibition of PARP1 enzymatic activity with olaparib abrogated the nuclear expression of APLF with loss in expression of genes associated with EMT. Thus, our findings reveal that cellular localization of APLF may predict the risk of breast cancer to metastasize and hence could be exploited to determine the disease progression. We anticipate that the inhibition of cytosolic PARP1-APLF interaction may potentially aid in the prevention of breast cancer metastasis in TNBC patients.

Climate change impacts on worldwide ecological niche and invasive potential of Sternochetus mangiferae.

Present climate studies on invasive species imply that climate change will alter the habitat suitability of invasive pests, especially given the projected rise in average global temperatures by the end of 2100. However, globally, limited information exists on the habitat suitability of the mango stone weevil, Sternochetus mangiferae Fabricius, which impedes the development of early detection and preventive measures. Herein, we used the MaxEnt model to estimate the potential global geographical distribution of S. mangiferae. Our results revealed that thermal conditions played a significant role in explaining the invasion risk of S. mangiferae. Habitat suitability was found in all continents, except Antarctica. Under the present condition, habitat suitability covered 5.67 × 107 km2. For ssp126, habitat suitability will decrease from the 2060s (5.58 × 107 km2) and 2080s (5.57 × 107 km2). Similarly, under ssp585, suitable areas will decrease from 5.62 × 107 to 5.51 × 107 km2 for the 2060s and 2080s, respectively. Our study has estimatedvariability in the habitat suitability of S. mangiferae which establishes a foundation for determining global riskassessment and response plans for the pest. This study also identifies areas where the pest is inherently more vulnerable to the impacts of changing climates and enables forecasting of its potential distribution in a dynamic world. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

AMIGO2 enhances the invasive potential of colorectal cancer by inducing EMT.

In our previous studies, we identified amphoterin-inducible gene and open reading frame 2 (AMIGO2) as a driver gene for liver metastasis and found that AMIGO2 expression in cancer cells worsens the prognosis of patients with colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) is a trigger for CRC to acquire a malignant phenotype, such as invasive potential, leading to metastasis. However, the role of AMIGO2 expression in the invasive potential of CRC cells remains unclear. Thus, this study aimed to examine AMIGO2 expression and elucidate the mechanisms by which it induces EMT and promotes CRC invasion. Activation of the TGFβ/Smad signaling pathway was found involved in AMIGO2-induced EMT, and treatment with the TGFβ receptor inhibitor LY2109761 suppressed AMIGO2-induced EMT. Studies using CRC samples showed that AMIGO2 expression was highly upregulated in the invasive front, where AMIGO2 expression was localized to the nucleus and associated with EMT marker expression. These results suggest that the nuclear translocation of AMIGO2 induces EMT to promote CRC invasion by activating the TGFβ/Smad signaling pathway. Thus, AMIGO2 is an attractive therapeutic target for inhibiting EMT and metastatic CRC progression.

Microbiome flexibility enhances the resilience of the potentially invasive coral Tubastraea aurea to abrupt environmental changes: Insights from a shallow water hydrothermal vent transplantation study

To comprehend the effects of potentially invasive coral Tubastraea aurea on marine ecosystems, it is crucial to understand their adaptive strategies to survive environmental changes and perturbations. Therefore, a cross-transplantation study was conducted to assess the microbiome's role in the resilience of T. aurea to sudden environmental changes.Hydrographic analyses revealed distinct ecological conditions at two sites: a hydrothermal vent (HV) site, characterized by harsh environmental conditions serving as a natural laboratory for future oceanic changes, and a regular coastal site Fulong (FU). Both sites showed significant differences in pH, temperature, and dissolved oxygen. Using Oxford Nanopore Technologies, we examined bacterial dynamics in coral tissue, mucus and ambient sediment samples following cross-transplantation experiments. We observed a rapid shift in dominant bacterial groups post-transplantation with transplanted corals acquiring microbiomes similar to native corals from their respective sites within 16 days. The bacteria Endozoicomonas euniceicola and Ruegeria profundi were dominant in both native and transplanted corals, suggesting their critical role in coral resilience. Furthermore, the enrichment of certain bacterial taxa post-transplantation suggests that opportunistic species also contribute to host acclimatization. Functional profiling data indicated that there was site-specific adaptation because corals had acquired beneficial bacterial assemblages to assist them cope with environmental stressors. More specifically, there was a switch towards sulfur and nitrogen metabolism in corals that moved to high sulfidic environments, while corals transplanted into normal coastal environments showed enriched photoautotrophic processes due to their symbionts. Our study underscored the highly flexible microbiome of T. aurea and its pivotal role in facilitating host resilience to environmental perturbations, particularly in the context of its potential invasiveness. Hence, these findings contribute to the understanding of coral-microbiome dynamics and emphasize the necessity of considering microbially-mediated resilience in managing potentially invasive coral species in marine ecosystems around the world, especially as ocean conditions continue to change.

Facilitators or predators? The role of seed-feeding beetles in the germination of an ornamental and invasive plant in an urban environment

Leucaena leucocephala is a forage legume that provides cellulose, firewood, and shade in cities, although it presents a dangerous allelopathic and invasive potential. Its main natural enemy is the endophytic beetle Acanthoscelides macrophthalmus (Chrysomelidae: Bruchinae), whose larvae penetrate seeds and can consume the entire endosperm and embryos. However, there is much to explore on how the abundance of larvae inside the seed affects the plant germination, resulting in an antagonistic (predation) or mutualistic (facilitation) interaction. Our goal was to test how these beetles affect the germination of L. leucocephala seeds from an urban environment in Uberlândia, MG. We hypothesized that a single larva inside the seed facilitates germination since the exit holes left break the physical dormancy and enable water imbibition. On the other hand, two or more larvae inside the same seed result in predation, as the amount of endosperm is not enough for beetle satiation before they attack the seed embryo. We collected 100 pods, dissected them, and quantified and qualified the seeds. In the germination experiment, we used healthy seeds (control), scarified healthy seeds (physical treatment), and attacked seeds (one, two, or more larvae). We found that beetles infested 74% of the sampled seeds. Independently of the abundance of larvae inside the seed, attacked seeds did not germinate. The scarified seeds germinate faster and in greater quantity. Therefore, our hypothesis was rejected for the studied plant population. Acanthoscelides macrophthalmus acts only as a predator in an antagonistic interaction that decreases the germination rate of L. leucocephala.

Production of biostable drinking water using a lab-scale biological trickling filter enriched with hydrogen-oxidizing bacteria

Safeguarding the drinking water quality remains a challenge from the production site to the tap. Alternatively to chemical disinfection, biostable drinking water could serve as a more sustainable approach to produce microbially safe drinking water and to maintain the microbial quality in the drinking water distribution system (DWDS). In this study, the potential of hydrogen-oxidizing bacteria (HOB) to produce biostable drinking water was examined in a continuous trickling filter supplied with hydrogen gas. A biofilm was naturally enriched for 5 months and the bacterial regrowth, invasion potential, and nutrient composition of the water were determined. Treatment improved the biostability significantly, and it is hypothesized that nutrient limitation, especially phosphorous, was a driving force. As a result, the regrowth and invasion potential were lowered, as shown with specific biostability bioassays. Overall, this study demonstrates the proof-of-concept of HOB for producing biostable drinking water through nutrient limitation.

Updates in Microglial Research with Respect to Brain Cancer

Microglia resides in the microenvironment of the central nervous system (CNS) and is thought to play a key role in the development and progression of brain cancer. This is because it was shown that microglia comprised a large portion of the total brain tumour mass. Besides, the origin of microglia cells in brain tumours is worth understanding as it is important to distinguish the resident macrophages from the circulating macrophages when discussing the pathology of brain tumours. Activated microgliosis has been linked to increased inflammatory mediators like cytokines, growth factors, matrix metalloproteinases (MMPs) and many more, which would facilitate tumourigenesis. Brain tumour cells also proliferate under the influence of signalling pathways, such as the toll-like receptor 2 signals. Vascular endothelial growth factor (VEGF) which is an angiogenic factor aids in the growth of tumour cells. Brain cancer cells rely on suppressing the effector arm of immune system to evade attacks by downregulating major histocompatibility complexes (MHC) class II molecules and inducing the conversion of microglia to an immunosuppressive phenotype. Glioblastoma stem cells (GSCs) that give rise to brain cancers communicate with microglia cells, which determines their growth and invasion potential. Understanding the molecular interactions of brain cancer and microglia cells would help unlock novel treatments via means of immunotherapy, immunosuppressants and utilising microglia cells to deliver nanoparticle drugs to effectively target and treat brain cancer.

Comparison of a Novel Posterior Integrated Transfixation Sacroiliac Joint Fusion Approach to the Posterolateral and Lateral Approaches: A Cadaveric Biomechanical and Computational Analysis of the Fixation, Invasiveness, and Fusion Area.

To concurrently assess and compare the fixation efficacy, invasiveness, and fusion potential of a posterior integrated transfixation cage system to the posterolateral threaded implant and lateral triangular rod systems, in a cadaveric model. Twelve (12) cadaveric sacroiliac joint specimens were utilized and tested within the single-leg stance multidirectional pure moment bending model. Each specimen was tested in the intact, destabilized, treated (using posterior, posterolateral, and lateral systems), and post-fatigue conditions by applying 0 to ± 7.5 Nm of moment in flexion-extension, axial rotation, and lateral bending while measuring the angular range of motion between the sacrum and ilium. Computational models were reconstructed from Computed Tomography (CT) scans and manufacturer surgical technique guides. The models were utilized to quantify the volume of bone removed during implantation and the surface area available for fusion. The posterior integrated transfixation cage system and the lateral triangular rods produced equivalent motion reduction in all motion planes (P > 0.583). The posterolateral cylindrical threaded implant produced less motion reductions than the posterior and lateral implants in flexion-extension (6% ± 3% vs 37% ± 10% and 33% ± 11%, respectively, P <0.05). The posterior system removed 22%-60% less bone volume from the sacrum and ilium (P<0.10), introduced 200%-270% more implant surface to the joint space (P<0.01) and decorticated 75%-375% more joint surface area (P<0.01). The posterior integrated transfixation single-implant cage system is superior to the posterolateral cylindrical threaded single-implant system. Its performance in osteopenic bone is equivalent to the lateral triangular rod system in healthy bone; however, the posterior integrated transfixation cage system requires a single implant, while the lateral triangular rod system requires three. The posterior implant removes the least bone volume and has the most surface area for fusion, providing a significantly better opportunity for robust sacroiliac joint arthrodesis.

MiR-4448/Girdin/Akt/AMPK axis inhibits EZH2-mediated EMT and tumorigenesis in small-cell lung cancer.

Small-cell lung cancer (SCLC) shows high enhancer of zeste homolog 2 (EZH2) expressions. EZH2-mediated epigenetics promote epithelial-mesenchymal transition (EMT), enhancing invasive and metastatic potential in malignancies. MicroRNAs (miRNAs), small noncoding RNAs, modulate EMT, determining tumor phenotypes. However, the association between miRNAs and EZH2 in SCLC remains to be clarified-we aimed to identify a novel tumorigenic mechanism through miRNAs, EZH2, and EMT in SCLC, leading to future therapeutic applications. We analyzed EZH2 and E-cadherin expressions in lung cancer cell lines and tumor tissues from 34 SCLC patients and confirmed EZH2 siRNA-mediated EMT inhibition. miRNA expression profiles were compared between EZH2 knockdown SCLC cells and negative control SCLC cells using miRNA array. We identified a target miRNA of EZH2 showing expressional differences in EZH2-knockdown cells and analyzed the impact of the miRNA on EZH2-mediated EMT and tumorigenesis. All SCLC cells showed increased EZH2 and decreased E-cadherin expressions. SCLC tissues had higher EZH2 and lower E-cadherin expressions than other lung cancer tissues. miRNA array revealed that miR-4448 expression increased in EZH2-knockdown SCLC cells. miR-4448 overexpression reduced tumor cell growth and prevented EMT. miR-4448 bound to the 3'UTR of the girdin gene and suppressed its expression, thereby decreasing Akt phosphorylation at Ser473. Attenuated Akt phosphorylation resulted in AMP-activated protein kinase (AMPK) phosphorylation at Thr172 and 183, enhancing EZH2 phosphorylation at Thr311. SCLC characterized high EZH2 expression and promoted EMT, compared with non-small cell lung cancer. miR-4448 inhibited Girdin expression, reducing Akt phosphorylation, and enhancing AMPK and EZH2 phosphorylation. Eventually, miR-4448 prevented EZH2-mediated EMT and tumorigenesis by modulating the Girdin/Akt/AMPK axis in SCLC. miR-4448 might be a potential SCLC inhibitor.

The expression level of VEGFR2 regulates mechanotransduction, tumor growth and metastasis of high grade serous ovarian cancer cells

Recent data shows that alterations in the expression and/or activation of the vascular endothelial growth factor receptor 2 (VEGFR2) in high grade serous ovarian cancer (HGSOC) modulate tumor progression. However, controversial results have been obtained, showing that in some cases VEGFR2 inhibition can promote tumorigenesis and metastasis. Thus, it is urgent to better define the role of the VEGF/VEGFR2 system to understand/predict the effects of its inhibitors administered as anti-angiogenic in HGSOC. Here, we modulated the expression levels of VEGFR2 and analyzed the effects in two cellular models of HGSOC. VEGFR2 silencing (or its pharmacological inhibition) promote the growth and invasive potential of OVCAR3 cells in vitro and in vivo. Consistent with this, the low levels of VEGFR2 in OV7 cells are associated with more pronounced proliferative and motile phenotypes when compared to OVCAR3 cells, and VEGFR2 overexpression in OV7 cells inhibits cell growth. In vitro data confirmed that VEGFR2 silencing in OVCAR3 cells favors the acquisition of an invasive phenotype by loosening cell-ECM contacts, reducing the size and the signaling of focal adhesion contacts (FAs). This is translated into a reduced FAK activity at FAs, ECM-dependent alterations of mechanical forces through FAs and YAP nuclear translocation. Together, the data show that low expression, silencing or inhibition of VEGFR2 in HGSOC cells alter mechanotransduction and lead to the acquisition of a pro-proliferative/invasive phenotype which explains the need for a more cautious use of anti-VEGFR2 drugs in ovarian cancer.

Assessing the climatic niche changes and global invasion risk of Solanum elaeagnifolium in relation to human activities

As an invasive plant, Solanum elaeagnifolium has posed a serious threat to agriculture and natural ecosystems worldwide. In order to better manage and limit its spread, we established niche models by combining distribution information and climate data from the native and invasive ranges of S. elaeagnifolium to analyze its niche changes during its colonization. Additionally, we evaluated its global invasion risk. Our results showed that the distribution of S. elaeagnifolium is affected by temperature, precipitation, altitude, and human activities. Solanum elaeagnifolium exhibits different degrees of niche conservatism and niche shift in different invasion ranges.During the global invasion of S. elaeagnifolium, both the niche shift and conservatism were observed, however, niche shift was particularly significant due to the presence of unoccupied niches (niche unfilling). Solanum elaeagnifolium generally occupied a relatively stable niche. However, a notable expansion was observed primarily in Europe and China. In Australia and Africa, its niche largely remains a subset of its native niche. Compared to the niche observed in its native range, its realized niche in China and Europe has shifted toward lower temperature and higher precipitation levels. Conversely, in Africa, the niche has shifted toward lower precipitation levels, while in Australia, it has shifted toward higher temperature. Our model predicted that S. elaeagnifolium has high invasion potential in many countries and regions. The populations of S. elaeagnifolium in China and Africa have reached the adapted stage, while the populations in Australia and Europe are currently in the stabilization stage. In addition, our research suggests that the potential distribution of S. elaeagnifolium will expand further in the future as the climate warms. All in all, our study suggests that S. elaeagnifolium has high potential to invade globally. Due to its high invasive potential, global surveillance and preventive measures are necessary to address its spread.

Scorpion mud turtle breeding in the Amazon: zootechnical and environmental activity for the species conservation

Commercial captive turtle breeding is an opportunity for Kinosternon scorpioides scorpioides conservation, as predatory hunting, destruction and habitat degradation are the main threats to its natural populations. In this sense, the goal of this study is to provide a synthesis of knowledge about the species Embrapa-developed captive breeding system. Below, we have set up the themes in a way that makes sense in the captivity flow, discussing important information about the species in the environmental context and its management from the initial breeding stock formation up to reproductive aspects, highlighting animal behaviour and the environmental approach of the activity, to support commercial breeding from the species conservation perspective. The discussion and conclusions have shown that the species has a low invasive potential in Brazilian biomes; the captivity site needs not much space, facilities or water; captive breeding is a zootechnical and environmentally appropriate activity for the species’ conservation because it is a way to avoid spending on programs that are made only for this purpose; and increasing knowledge of reproduction using molecular genetic tools is important. Keywords: conservation, chelonian, Kinosternon scorpioides, jurará, turtle breeding

Analytical prediction model for edge water invasion flow rate in SAGD heavy oil reservoirs

SAGD (Steam Assisted Gravity Drainage) technology is a highly developed method for the extracting heavy oil. In the Liaohe Oilfield in China, there are 72 SAGD well groups within a massive heavy oil reservoir containing edge water and the risk associated with edge water invasion is substantial. Currently, the injected steam is less than 50 m away from the edge water, which increases the urgency to address the potential invasion of edge water. If the edge water flows into the reservoir, it will impact nearly 8.0 × 105 tons of crude oil production. Recognizing the importance of mitigating the edge water invasion, this paper proposes a prediction model for the edge water invasion flow rate in SAGD reservoirs. The model integrates mass and heat transfer dynamics between the steam chamber and edge water, the relative permeabilities of oil and water phases, and the viscosity-temperature relationship of water. The model is validated through numerical simulations and field data. The findings indicate that for SAGD reservoirs with a permeability greater than 1 D, maintaining a minimum distance of 25 m between the edge water and the steam chamber is advisable, especially when the pressure differential is 0.5 MPa. Furthermore, the prediction model is used to forecast the edge water breakthrough time and evaluate water invasion risk. A prediction chart for the edge water invasion flow rate is developed, providing a practical tool for estimating invasion flow rate curves. Also, a method of edge water invasion warning is established, with a corresponding chart that offers a quick assessment of water invasion risks in heavy oil reservoirs. Overall, this research lays a foundational framework for understanding and managing the edge water invasion in SAGD operations, offering critical insights for the future study aimed at addressing the challenge posed by edge water in heavy oil reservoirs.

The Biology of Invasive Native Plant as an Ex-situ Collection: A Case Study of Epipremnum pinnatum (L.) Engl. (Araceae) in Bogor Botanical Garden, Indonesia

The Bogor Botanical Garden (BBG) is a pivotal center for plant research and conservation, boasting a diverse collection of over 12,000 individual plants spanning various species. However, among the plant collections at BBG, some of them have the potential to be invasive. Therefore, this study aimed to uncover the plant collections at BBG with invasive potential and analyze the distribution of one of the most dominant collections, Epipremnum pinnatum (L.) Engl. The method employed in this research involved a literature review to identify which plant collections have invasive potential and a vegetation analysis on the distribution of E. pinnatum within BBG. Additionally, ANOVA analysis and regression models were employed to explore the relationship between environmental factors and E. pinnatum abundance. Results revealed that BBG hosted 78 potentially invasive plant species, with E. pinnatum comprising 28 individuals. Spatial analysis indicates a clustered distribution of E. pinnatum, influenced by seed dispersal mechanisms, environmental factors, and biotic interactions. Correlation analysis links soil pH, soil moisture, and canopy cover to E. pinnatum distribution. Canopy cover demonstrates a significant positive correlation with E. pinnatum abundance, suggesting its importance in providing favorable microclimates for growth. Regression analysis further supports canopy cover as a predictor of E. pinnatum presence. However, while a strong statistical association was observed, causal relationships require further investigation. This study underscores the complexity of ecological dynamics in BBG and emphasizes the need for comprehensive research to define underlying mechanisms driving plant distributions and interactions.

Interconnections within the tumor microenvironment: extracellular vesicles as critical players of metabolic reprogramming in tumor cells

Metabolic reprogramming is an intrinsic characteristic of cancer, contributing to its establishment and progression, survival, high proliferation rates, and increased migratory and invasive potential; tumor cells establish an intimate relationship with the surrounding microenvironment, where sustained communication allows the stromal fraction of the tumor microenvironment (TME) to supply energetic substrates and facilitate the biosynthesis of macromolecules, thereby promoting tumor progression. In this context, extracellular vesicles (EVs) emerge as potential communication vehicles, carrying inside content reflecting the cellular environment of origin and thus modulating the phenotype of recipient cells. The potential of EVs as modulators in the TME has been highlighted and is now consensual; however, most available articles have focused on revealing the effect of EVs in modulating tumor phenotypes and signaling pathways in tumor cells. Regarding the metabolic modulation sustained by EVs, studies have demonstrated the role of cancer cells’ EVs as modulators of surrounding cells, like immune cells, fibroblasts, and adipocytes. Therefore, this review aims to: i. highlight the most recent studies evaluating the role of cellular vesicles released by those cells within the microenvironment in the metabolic reprogramming of cancer cells; ii. compile scientific evidence proposing how EVs could modulate the metabolic profile of tumor stem cells and lymphocytes, particularly given the lack of studies focused on such approaches; and iii. highlight possible effects of vesicles, as the metabolic modulation induced by these vesicles could have anticancer potential.

Orbital solitary fibrous tumor

Introduction: Solitary fibrous tumor (SFT) is a rare borderline mesenchymal tumor typically arising in the pleura and involving the orbit as its most common extra-pleural locationCase description: We herein describe two cases of orbital SFT arising in both a 69-year-old woman presenting with progressive proptosis of the left eye and a 49-year-old woman presenting with binocular diplopia. The diagnoses relied on histopathological analysis of biopsy samples. Because of the poor local prognosis, we decided to perform an orbital exenteration in the first case. In the second case, a complete resection surgery was performed.Conclusion: SFT presents classics histological features and immunohistochemical markers that are essential to the diagnosis.SFT is classified as a benign tumor, but in some cases, it can show aggressive behavior with the potential for local tissue invasion and, more scarcely, distant metastasis. This is why complete resection remains the treatment of choice for SFT.

How Does Cancer Occur? How Should It Be Treated? Treatment from the Perspective of Alkalization Therapy Based on Science-Based Medicine.

This review article investigates the relationship between mitochondrial dysfunction and cancer progression, emphasizing the metabolic shifts that promote tumor growth. Mitochondria are crucial for cellular energy production, but they also play a significant role in cancer progression by promoting glycolysis even under oxygen-rich conditions, a phenomenon known as the Warburg effect. This metabolic reprogramming enables cancer cells to maintain an alkaline internal pH and an acidic external environment, which are critical for their proliferation and survival in hypoxic conditions. The article also explores the acidic tumor microenvironment (TME), a consequence of intensive glycolytic activity and proton production by cancer cells. This acidic milieu enhances the invasiveness and metastatic potential of cancer cells and contributes to increased resistance to chemotherapy. Alkalization therapy, which involves neutralizing this acidity through dietary modifications and the administration of alkalizing agents such as sodium bicarbonate, is highlighted as an effective strategy to counteract these adverse conditions and impede cancer progression. Integrating insights from science-based medicine, the review evaluates the effectiveness of alkalization therapy across various cancer types through clinical assessments. Science-based medicine, which utilizes inductive reasoning from observed clinical outcomes, lends support to the hypothesis of metabolic reprogramming in cancer treatment. By addressing both metabolic and environmental disruptions, this review suggests that considering cancer as primarily a metabolic disorder could lead to more targeted and effective treatment strategies, potentially improving outcomes for patients with advanced-stage cancers.

Combination treatment with histone deacetylase and carbonic anhydrase 9 inhibitors shows therapeutic potential in experimental diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) remains a significant therapeutic challenge due to the lack of effective and safe treatment options. This study explores the potential of combining histone deacetylase (HDAC) and carbonic anhydrase 9 (CA9) inhibitors in treating DIPG. Analysis of RNA sequencing data and tumor tissue from patient samples for the expression of the carbonic anhydrase family and hypoxia signaling pathway activity revealed clinical relevance for targeting CA9 in DIPG. A synergy screen was conducted using CA9 inhibitor SLC-0111 and HDAC inhibitors panobinostat, vorinostat, entinostat, and pyroxamide. The combination of SLC-0111 and pyroxamide demonstrated the highest synergy and was selected for further analysis. Combining SLC-0111 and pyroxamide effectively inhibited DIPG cell proliferation, reduced cell migration and invasion potential, and enhanced histone acetylation, leading to decreased cell population in S Phase. Additionally, the combination therapy induced a greater reduction in intracellular pH than either agent alone. Data from this study suggest that the combination of SLC-0111 and pyroxamide holds promise for treating experimental DIPG, and further investigation of this combination therapy in preclinical models is warranted to evaluate its potential as a viable treatment for DIPG.

Limited population structure but signals of recent selection in introduced African Fig Fly (Zaprionus indianus) in North America.

Invasive species have devastating consequences for human health, food security, and the environment. Many invasive species adapt to new ecological niches following invasion, but little is known about the early steps of adaptation. Here we examine population genomics of a recently introduced drosophilid in North America, the African Fig Fly, Zaprionus indianus. This species is likely intolerant of subfreezing temperatures and recolonizes temperate environments yearly. We generated a new chromosome-level genome assembly for Z. indianus. Using resequencing of over 200 North American individuals collected over four years in temperate Virginia, plus a single collection from subtropical Florida, we tested for signatures of recolonization, population structure, and adaptation within invasive populations. We show founding populations are sometimes small and contain close genetic relatives, yet temporal population structure and differentiation of populations is mostly absent across recurrent recolonization events. Although we find limited signals of genome-wide spatial or temporal population structure, we identify haplotypes on the X chromosome that are repeatedly differentiated between Virginia and Florida populations. These haplotypes show signatures of natural selection and are not found in African populations. We also find evidence for several large structural polymorphisms segregating within North America populations and show X chromosome evolution in invasive populations is strikingly different from the autosomes. These results show that despite limited population structure, populations may rapidly evolve genetic differences early in an invasion. Further uncovering how these genomic regions influence invasive potential and success in new environments will advance our understanding of how organisms evolve in changing environments.

Investigation of the distribution patterns in moinids (Crustacea: Cladocera: Moinidae) forming ephippia with two resting eggs

During last two decades, morphological and genetic studies of the microcrustaceans from the family Moinidae Goulden, 1968 (Crustacea: Branchiopoda: Cladocera) were intensified. However, species diversity within this family remains underestimated. It refers to both subtropical and tropical areas of different continents that have traditionally been less studied compared with Central Europe and some other Palaearctic regions. In addition to this, only a restricted set of morphological characteristics is used for the discrimination of species within the genus Moina Baird, 1850. Most common moinid taxa are considered species complexes rather than single species, making any biogeographic reconstruction difficult. Here, we present an investigation of distribution patterns in moinids that form ephippia with two resting eggs based on both a reexamination of data from the literature and from specimens in museum and personal collections. Also, we redescribed morphology of poorly known taxa from the arid regions of the Old World—Moina belli Gurney, 1904 and M. kaszabi Forró, 1988 and clarify their diagnostic morphological characters and distributional ranges. We found that M. belli and M. kaszabi are morphologically very similar. In both species, setae 1 and 2 of thoracic limb I are armed bilaterally by fine, densely located short setulae. Reliable differences between M. belli and M. kaszabi concern armature of the valve posteroventral portion. Among the moinids with two resting eggs in the ephippium, M. belli and M. kaszabi are morphologically closer to M. macrocopa (Straus, 1820) and M. americana Goulden, 1968. All these species have: (1) a dorsal head pore; (2) fine long hairs on head, valve and preanal margin of postabdomen; (3) thoracic limb I of male with a long exopodite. In general, an investigated group of moinids includes both species with relatively compact and very broad distributional ranges. We concluded that maximum diversity of the moinids forming ephippia with two resting eggs is characteristic of southern portions of Palaearctic and Nearctic zoogeographical regions and approximately corresponds to subtropical climate zone. We need to underline that M. macrocopa and M. americana have a great invasive potential. Both species were anthropogenically introduced in South America and have been successfully naturalized there. Their distribution in tropical regions of the Old World and Australia requires new precise investigations. A group of moinids forming ephippia with two resting eggs can be considered as a convenient model for biogeographical reconstructions, including studies on changes in aquatic ecosystems due to global climate warming, eutrophication and the introduction of non-native species. There is no doubt that subsequent joint application of morphological and genetic data will shed more light on the global phylogeographic structure of the entire family Moinidae.