Landscape Of Alterations Research Articles

Alternations of N6-methyladenosine RNA methylation landscape in pulmonary arterial hypertension

Abstract Background N6-methyladenosine (m6A) methylation is the most prevalent and abundant RNA modifications in eukaryotes. Deregulation of m6A changes by m6A-specific enzymes can affect the stability and function of transcripts. However, the relevance of m6A mRNA and m6A-specific enzymes in pulmonary arterial hypertension (PAH) have not been extensively explored. Objectives This study aimed to analyze m6A methylation transcriptomic profiling in the pulmonary arteries of PAH rats, and to find potential m6A regulators corelated with PAH epi-transcriptomic changes. Methods MeRIP-seq and RNA-seq were applied to identify differences in m6A methylation and gene expression in pulmonary artery tissues from control and monocrotaline PAH rats. The expression of a m6A regulator in pulmonary arteries was further analyzed by western blot, flow cytometry, immunohistochemical staining and immunofluorescence. The proliferation and apoptosis assays were further performed in primary rat pulmonary artery smooth muscle cells (PASMCs). Results Twenty-seven differentially expressed genes with hypermethylated or hypomethylated m6A modifications were identified. These differentially expressed genes were mainly linked to the extracellular matrix and structure, MAPK and PI3K-Akt signaling pathways. Furthermore, we firstly detected a m6A reader leucine rich pentatricopeptide repeat containing (LRPPRC) with downregulated expression in PAH rats. PASMCs with a siRNA knockdown of the LRPPRC promoted proliferation and apoptotic resistance. Conclusion This study showed that altered m6A transcriptome-wide landscape and relevant regulatory mechanisms of the PAH pulmonary artery tissues in rats, which might provide a new and potential target for therapeutic interventions in PAH.LRPPRC functional studies in PASMCs

Abstract 15845: Unraveling Postoperative Atrial Fibrillation at the Single-Cell Level

Background: Postoperative atrial fibrillation (poAF) is one of the most common complications after cardiac surgery. It increases the length of stay in the ICU and hospital, increases the risk of stroke, and leads to death. Several clinical factors, including age, obesity, and co-occurring conditions such as prior atrial fibrillation, hypertension, kidney disease, etc., are associated with poAF. We hypothesize that the atrial transcriptome differs between patients who remain in sinus rhythm following surgery and those who develop poAF, allowing the identification of genes, pathways, and cell types necessary for the understanding and treatment of poAF. Methods: Single-cell RNA sequencing (scRNA-seq) was performed to gain insights into the heterogeneous cell populations of the left atrium. It provided an in-depth view of the variability in the cellular response to poAF through the molecular changes within cells, allowing for identifying biomarkers and therapeutic targets. Changes in gene expression associated with poAF were modeled, including batch, sex, age, atrial size, and history of atrial fibrillation and covariates. Results: sc-RNA-seq data of thirty-one human left atrium samples were analyzed. The samples included 14 females and 17 males aged 35-86 years. Cell clusters were identified after the quality check, preprocessing, and normalization. Nine distinct cell types were identified, including atrial cardiomyocytes, fibroblasts, endothelial cells, smooth muscle cells, adipocytes, pericytes, myeloid, lymphoid, and neuronal cells. The atrial cardiomyocytes and fibroblasts were the most abundant identified cell types. The enrichment of these cell types and significant changes in many marker genes in the disease condition suggest their crucial role in their response to the disease. Conclusion: The comprehensive analysis revealed distinct gene expression patterns and cellular heterogeneity. It provided valuable insights into the cellular landscape and transcriptional alterations in poAF. By shedding light on the molecular mechanisms, the findings pave the way for developing targeted interventions to mitigate the impact of poAF.

DIGITALIZATION OF HIGHER EDUCATION

For an extended period, the higher education community has been diligently endeavoring to implement technologically advanced and more efficacious methodologies. The aim is to enhance effectiveness and cultivate a generation of graduates equipped to navigate the evolving labor market dynamics and adapt to the influences of globalization. The outbreak of the Covid-19 pandemic significantly catalyzed the adoption of digital education, often referred to as "E-Learning," as a predominant mode of instruction across a majority of countries. This shift was necessitated by the imperative to adhere to social distancing measures and prevent the potential collapse of the educational infrastructure. In the wake of this transformative paradigm, educational institutions were compelled to engineer inventive management approaches to effectively traverse this altered landscape, marking the dawn of a new era. This era is characterized by a profound dependence on advanced technology and unfettered information accessibility as pivotal factors for sustaining and optimizing performance.This paper aims to explain the basic ideas behind managing higher education while exploring the existing research that supports these ideas. By breaking down the various aspects and tools involved, the goal is to shed light on the complex nature of managing higher education. This exploration eventually leads to an examination of how the digitalization of education impacts different functional areas of education management. Through this in-depth analysis, a clear connection emerges between the need for digitalization and the necessity to update management systems. This connection is crucial for not only achieving but also sustaining effective operation in this new era that combines technology and education.

Balancing development and sustainability: Assessing risks and protecting aquatic biodiversity on US college and university campuses

AbstractExtensive urbanization impairs biological communities through landscape alteration and physiochemical changes to stream ecosystems. Analogous to urban development in cities, new building and facility expansion on university campuses can lead to dramatic changes in impervious cover and consequently, increased stormflow impacting downstream ecological communities. Here, we analyze the extent and relevance on a nationwide scale to determine campuses with the highest risk for ecological impairment. From the US‐wide analysis of 5761 college/university campuses, ~45% of campuses were within critical aquatic species watersheds, and >5% were identified as buffering critical habitat. The highest risk campus our study identified was selected to compare the impacts of planned, conventional development versus sustainable development on a sensitive aquatic species, the federally threatened Jollyville Plateau salamander (Eurycea tonkawae). Impervious cover, simulated increases in stormwater runoff, and total suspended solids (TSS) from the conventional expansion is estimated to lower salamander density. Conversely, an alternative campus expansion plan allowed for increased development but permitted provisions for reduced runoff and TSS, thereby maintaining current salamander densities. Our findings show that sustainable campus development plans have the potential to mitigate ecological disruption within watersheds, and that campus management and policies are critical for preserving biodiversity in the future.

Transcription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape

Introduction: Acquired mutations, most commonly in RNA splicing factors and epigenetic regulators are thought to be disease drivers of clonal myeloid disorders such as MDS and AML. Both MDS and AML are amenable to epigenetic therapies regardless of underlying mutational subtypes. This prompted our hypothesis that alterations to epigenetic and chromatin landscape is important in pathobiology of clonal myeloid disorders driven by splicing factor mutations. In this study, we demonstrate that SF3B1 mutations induce distinct changes to epigenetic landscape and chromatin organization by altering RNA Polymerase II (Pol2) transcription kinetics. Critically, such epigenetic changes are also targetable - inhibiting components in the H3K4me/Sin3/HDAC pathway reverses Pol2 transcription defects and downstream effects on chromatin organization and genomic integrity. Methods: We generated inducible isogenic K562 cell lines that express single mutant allele of SF3B1 K700Ecombining two genome editing approaches (AAV-intron trap with CRISPR/Cas9 (Boddu et al, Comms Biol, 2021)) (Fig1A). RNAPII transcription kinetics changes were assessed using ChIP-seq for Pol2 and nascent-transcriptome assays (including GRO-seq and transient transcriptome-time lapse sequencing (TT-TL-seq). Chromatin accessibility/nucleosome density and histone marks (H3K4me3, H3K27ac, H3K27me3) were assessed using ATAC-seq and low-input CUT&RUN, respectively. Key results were replicated in patient samples with SF3B1 mutations and in a Sf3b1K700E mouse model. Results: Combining genome-wide approaches (ChIP-seq (Fig1B), GRO-seq, and TT-TL seq (Fig1C)), we found that Pol2 in SF3B1 K700E redistributes into the gene body due to a primary gene-body elongation defect. This transcriptional dysregulation was reflected in downstream effects such as excess R-loops (S9.6 microscopy; Fig1D), transcription-replication conflicts (proximity ligation assay for PCNA-Pol2; Fig1E), and S-phase arrest (flow cytometry; Fig1F). Importantly, normalized Pol2 density at proximal-promoter (p-p) region was reduced in SF3B1 K700E (Fig1G). This correlated with a reduction in p-p H3K4me3 in SF3B1 K700E determined by Cut and Run (Fig1H). ATAC-seq showed a reduction in promoter accessibility (Fig1I) and increased nucleosome promoter density (Fig1J). ChIP-seq for CDK9, a component of p-TEFb pause release complex, showed higher occupancy at promoters in SF3B1 K700E (Fig1K), suggesting that premature promoter pause release of Pol2 is the major driver for the observed reduction in p-p Pol2 density. Consistent with the importance of p-p Pol2 in maintaining accessible chromatin states, our findings suggest that depletion of p-p Pol2 leads to nucleosome repositioning at promoters and loss of chromatin accessibility (Gilchrist et al, Cell, 2010). Given the extensive cross talk between chromatin and transcription, we speculated that modulating epigenetic regulators might improve Pol2 elongation defects and rescue cells from downstream effects. An unbiased shRNA rescue screen, targeting epigenetic regulators and chromatin modifier protein classes, enriched for proteins in the Sin3/HDAC pathway (ING2, HDAC2) (Fig1L). Conversely, knocking down (KD) for WDR5 (H3K4me3 writer complex) further worsened survival. HDAC2 and ING2 KD cells showed reduced R-loops and DNA damage, lower gene-body Pol2 ChIP densities (Fig1M), normalization of p-p H3K4me3 densities (Fig1N), and rescue from S-phase arrest. These effects of WDR5 and HDAC2/ING2 KD on survival in SF3B1-mutant isogenic cells was confirmed in both MDS patient samples (Fig1O)- and Sf3b1K700E murine models (Fig1P)- contexts, using in vitro colony assays. Conclusion: Our findings show that SF3B1 K700E-induced disruption of Pol2 elongation kinetics is reflected in reduced Pol2 density at proximal promoter sites and results in a corresponding reduction in chromatin accessibility and promoter H3K4me3. Through an unbiased shRNA screen, we identified epigenetic factors in the Sin3/HDAC/H3K4me pathway, which, when modulated, improved the transcription defects and their downstream effects. Our findings shed light on the mechanisms by which oncogenic mutant spliceosomes affect chromatin organization through their effects on Pol II transcription elongation and present a rationale for targeting the Sin3/HDAC complex as a potential therapeutic strategy.

Epigenetic and Transcriptional Consequences of PIM Kinase Activity and Inhibition in Diffuse Large B-Cell Lymphoma (DLBCL)

The PIM kinase family consists of 3 proto-oncogenic proteins: PIM1, PIM2 and PIM3, expressed in numerous malignancies, including DLBCL. PIM kinases regulate crucial processes, such as proliferation, apoptosis, metabolism, or migration, therefore their inhibition is of great interest as a potential therapeutic strategy. Although recent studies have shed new light on the biological role of PIMs in lymphoid cancers, the details and mechanisms of PIM's oncogenic effects and the consequences of their inhibition in DLBCL remain insufficiently understood. Earlier studies have demonstrated a potential epigenetic role of PIM through histone H3S10 phosphorylation, however, described only at a single locus. The broad genomic role of PIM in modulating transcription in lymphoma cells remains unclear. We confirmed the effect of PIM inhibition on histone modifications using small molecule inhibitors as well as genetic silencing of PIM kinases in DLBCL cell lines. PIM kinase inhibition changed the global amounts of histone modifications (including histone H4 pan-acetylation), accompanied by lower phosphorylation of RNA polymerase II, suggesting an involvement of PIMs in the RNA polymerase II pause release/elongation phase of transcription. Local histone acetylation changes in the enhancer (H3K27ac) and promoter (H3K9ac) regions in response to treatment with the pan-PIM inhibitor were also identified, coupled with gene expression profiling in DLBCL cell lines. PIM inhibition decreased the expression of genes controlled by super-enhancers (SE), i.e. wide regulatory regions responsible for the high level of expression of the most important genes for the cell, including oncogenes. The integrated results of epigenomic and transcriptomic analyses explain the changes in expression of genes associated with many pathways, including transcription, inflammatory response, apoptosis, epigenetic mechanisms or DNA damage. The induction of the latter was further experimentally confirmed by the examination of DNA breaks using γH2AX, the activating phosphorylation of CHK2 or comet assays following PIM inhibition. The conducted studies document an epigenetic function of PIM kinases, and suggest that inhibition of PIM activity leads to alterations in the DLBCL epigenetic landscape and associated changes in transcription. They also indicate that PIM inhibitors can be a therapeutic option in DLBCL. Study supported aby Foundation For Polish Science TEAM Grant # POIR.04.04.00-00-5C84/17 and Polish National Science Centre Grant # 2018/29/B/NZ5/01471.

Genomic Profiles and Associated Survival Prognosticators in Black Patients with Acute Myeloid Leukemia

Background Our knowledge of the genomics of acute myeloid leukemia (AML), which serves as the basis of clinically used prognostic biomarkers and therapeutic advances (including targeted therapies), is almost exclusively based on data from patients (pts) of European ancestry. Methods We analyzed the exomes and transcriptomes of 100 Black AML pts at diagnosis who received intensive induction chemotherapy on Alliance for Clinical Trials in Oncology (Alliance) protocols. African Ancestry was confirmed by SNP analysis. We established their genetic landscape including somatic gene mutations, structural variants, gene fusions and associated gene expression. Somatic mutation frequency was compared to whole-exome sequencing of 741 White pts at diagnosis from the Beat AML cohort analyzed by identical workflow. Survival of Black pts was compared to 1,519 White pts treated on the same Alliance protocols. Multivariable analysis was used to identify clinical and molecular features associated with outcomes. Results We identified 162 recurrently mutated genes in Black AML pts. We detected different mutation frequencies for AML-associated genes based on ancestry, and mutations in genes not previously implicated in AML, including PHIP alterations in 7% of this cohort. 38 genes were mutated in 3-5% of Black pts but in <1% of White pts . Of the 162 recurrently mutated genes in Black pts, only 41 (25%) were recurrently mutated in White pts, while 121 genes (75%) were mutated in ≤1 White patient. Only 1/741 White AML pts did not have a mutation in at least 1/ 56 recurrently mutated AML genes assessed by clinical NGS panels. By comparison, 10% of Black pts had no mutations in these genes. Analysis of gene fusions showed recurrent, cryptic CBFA2T3 fusions in 4 pts and a recurrent GGNBP2:: MYO19 fusion involving chromosome 17 not previously described in AML in 2 pts. The CBFA2T3 fusions did not cluster with CBF-AMLs by gene expression, suggesting biological differences. t-SNE visualization of gene expression showed that Black and White AML pts clustered together by known driver mutations. We identified a t-SNE cluster enriched for pts with myelodysplasia-related (MR) mutations. Notably, Black pts in this cluster were significantly younger than White pts [50 vs 58-years (y), p=0.04], suggestive of intrinsic and/or extrinsic dysplasia-causing stressors. When matched for age, performance status and study date, Black pts had higher relapse rates (63% vs 48%, p=0.05), worse disease-free (DFS, 3-y rates, 30% vs 47%, p=0.01) and overall survival (OS, 3-y rates, 31% vs 47%, p=0.007) compared to White pts. In a multivariable analysis, MR mutations (HR=2.06, p=0.03) and mutations in NPM1 (HR=2.29, p=0.009) and NRAS (HR=1.95, p=0.04) were associated with shorter DFS. Using the recently published iScore as a proxy for inflammation, we detected an enrichment of high inflammation in Black pts harboring NPM1 mutations compared to Whites (iScore high vs low; Black, 69% vs 31%, White, 45% vs 55%; p=0.08). Furthermore, when we classified pts into LSC17 prognostic groups, only 13% of Black pts in the prognostically favorable low LSC17 group were NPM1-mutated, compared with to 38% of White pts, suggesting ancestry-associated differences in the biological impact of NPM1 mutations. Mutations in IDH1/2 associated with shorter OS (HR=1.73, p=0.05) in Black pts identifying ancestry-specific risk markers. Finally, we show that the current ELN 2022 risk stratification system can be significantly improved by including NPM1, NRAS and IDH1/2 mutations as ancestry-specific adverse risk markers for Black pts ( Figure 2). Mutations in NPM1, NRAS, and IDH1/2 were enriched in a cohort of 43 Black relapsed/refractory (R/R)-AML pts via MSK-IMPACT supporting their adverse prognostic risk in Black pts. Conclusions Our work demonstrates ancestry-related differences in the genomic profiles of AML pts and calls for additional studies of ancestry-diverse populations to understand the landscape of somatic genetic alterations in AML. Further, our results emphasize the need to include ancestry-associated variants in clinical testing panels and to refine genetic risk assessment of AML by incorporating ancestry-specific prognostic biomarkers. Support: U10CA180821, U10CA180882, U24CA196171; Clinicaltrials.gov Identifiers: NCT00048958, NCT00899223, NCT00900224. https://acknowledgments.alliancefound.org.

Unraveling the impact of sialic acids on the immune landscape and immunotherapy efficacy in pancreatic cancer

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Despite the successful application of immune checkpoint blockade in a range of human cancers, immunotherapy in PDAC remains unsuccessful. PDAC...

PRRX1 Is a Master Regulator of Renal Fibroblast Cell Fate and Regulates Myofibroblast Activation in Response to TGF-β via Alteration of the Chromatin Landscape

PRRX1 Is a Master Regulator of Renal Fibroblast Cell Fate and Regulates Myofibroblast Activation in Response to TGF-β via Alteration of the Chromatin Landscape

336MO Genetic landscape and prognostic value of IRF4 alterations in diffuse large B cell lymphoma patients

336MO Genetic landscape and prognostic value of IRF4 alterations in diffuse large B cell lymphoma patients

EP03.06-03 The Landscape of NF1 Alteration in Chinese Non-Small-Cell Lung Cancer Patients

EP03.06-03 The Landscape of NF1 Alteration in Chinese Non-Small-Cell Lung Cancer Patients

Land use influences the nutrient concentration and composition of pollen and nectar rewards of wildflowers in human-dominated landscapes

Plant biodiversity is crucial to satisfy the trophic needs of pollinators, mainly through nectar and pollen rewards. However, a few studies have been directed to ascertain the intraspecific variation of chemical features and the nutritional value of nectar and pollen floral rewards in relation to the alteration of landscapes due to human activities. In this study, by using an existing scenario of land use gradients as an open air laboratory, we tested the variation in pollen and nectar nutrient profiles along gradients of urbanization and agriculture intensity, by focusing on sugar, aminoacids of nectar and phytochemicals of pollen from local wild plants. We also highlighted bioactive compounds from plants primary and secondary metabolism due to their importance for insect wellbeing and pollinator health. We surveyed 7 different meadow species foraged by pollinators and common in the main land uses studied. The results indicated that significant variations of nutritional components occur in relation to different land uses, and specifically that the agricultural intensification decreases the sugars and increases the antioxidant content of flower rewards, while the urbanization is positively associated with the total flavonoid content in pollen. These effects are more evident in some species than in others, such as Lotus corniculatus L. (Fabaceae) and Malva sylvestris L. (Malvaceae), as shown by the untargeted metabolomic investigation. This study is crucial for understanding the nutritional landscape quality for pollinators in association to different land uses and sets a base for landscape management and planning of pollinator-friendly strategies by improving the quality of plant rewards to provide benefits to pollinator health in various environmental contexts.

Sustainable land-use/Land-cover for stormwater management in three coastal watersheds in central Chile

ABSTRACT Central Chile’s Concon City urbanization trend has severely affected local hydrological processes. This research hypothesizes that switching to sustainable land-use/land-cover (LULC) in three Concon watersheds reduces the severity of their corresponding hydrological responses. High sustainability LULC zones would decrease runoff and enhance interception and infiltration, generating hydrograph curves with extended lag time and moderate peak flows. The Hydrological Simulation Program FORTRAN (HSPF) is used for simulating watershed processes. Decreases in peak flows of 31.1%, 19.8%, and 54.5%, were estimated. Therefore, sustainable LULC reduces the severity of the hydrological responses, benefiting storm water management. Real-world applications in Europe and the USA achieved comparable results. Urban master plans in Chile have favored the alteration of natural landscapes (anthropization). Per national regulations, changes to urban plans can be made every ten years. The results of this research will be valuable in future revisions of Concon’s urban plan.

Using Opportunistic Samples to Monitor West Nile Virus Infection Status in Greater Sage-grouse (Centrocercus urophasianus) in Wyoming, USA (2020-22).

The frequency of arthropod-borne viral disease in naïve hosts is subject to change based on complex interactions among vector, host, virus, and external factors (e.g., climate). Thus, continual monitoring for both disease susceptibility and host infection dynamics is needed, especially for viruses that have proven detrimental to the health of wildlife hosts of conservation concern. The Greater Sage-grouse (Centrocercus urophasianus) is a gamebird of ecological and economic importance in the western United States for which population declines have led to a Near Threatened conservation status. Although these declines have mainly been attributed to habitat loss, West Nile virus (WNV) also poses a threat, with regional transmission potentially fueled by anthropogenic landscape alterations that may facilitate mosquito breeding. With limited WNV monitoring in Greater Sage-grouse after recognition of high susceptibility to mortality early after its initial detection in the western United States, the potential long-term impacts of WNV on this species are poorly understood. We used the plaque reduction neutralization test of filter paper strip-eluted sera to assess for anti-WNV antibodies, indicating prior infection, in opportunistically collected samples. From 2020 to 2022, 85 Greater Sage-grouse in Wyoming were sampled; none had anti-WNV antibodies. This result corroborates findings of previous studies documenting low seroprevalence. With the tenuous conservation status of the species, all potential population health risks should be considered in future management strategies, especially in the face of changing climate and landscapes.

COVID-19 as a chronic stressor and the importance of individual identity: A data-driven look at academic productivity during the pandemic

The COVID-19 pandemic impacted personal and professional life. For academics, research, teaching, and service tasks were upended and we all had to navigate the altered landscape. However, some individuals faced a disproportionate burden, particularly academics with minoritized identities or those who were early career, were caregivers, or had intersecting identities. As comparative endocrinologists, we determine how aspects of individual and species-level variation influence response to, recovery from, and resilience in the face of stressors. Here, we flip that framework and apply an integrative biological lens to the impact of the COVID-19 chronic stressor on our endocrine community. We address how the pandemic altered impact factors of academia (e.g., scholarly products) and relatedly, how factors of impact (e.g., sex, gender, race, career stage, caregiver status, etc.) altered the way in which individuals could respond. We predict the pandemic will have long-term impacts on the population dynamics, composition, and landscape of our academic ecosystem. Impact factors of research, namely journal submissions, were altered by COVID-19, and women authors saw a big dip. We discuss this broadly and then report General and Comparative Endocrinology (GCE) manuscript submission and acceptance status by gender and geographic region from 2019 to 2023. We also summarize how the pandemic impacted individuals with different axes of identity, how academic institutions have responded, compile proposed solutions, and conclude with a discussion on what we can all do to (re)build the academy in an equitable way. At GCE, the first author positions had gender parity, but men outnumbered women at the corresponding author position. Region of manuscript origin mattered for submission and acceptance rates, and women authors from Asia and the Middle East were the most heavily impacted by the pandemic. The number of manuscripts submitted dropped after year 1 of the pandemic and has not yet recovered. Thus, COVID-19 was a chronic stressor for the GCE community.

Life Cycle Assessment of Sustainable Road Networks: Current State and Future Directions

The construction sector is one of the leading global contributors to environmental footprint, with road infrastructures being a significant resource consumer. The traditional practice of using virgin raw materials and extracting natural aggregates has a significant impact, causing landscape alterations and disruptions to ecosystems. As result, the focus on achieving sustainable mobility through road networks is increasing. Companies operating in the civil sector must consider the environmental performance of roads to inform their decision making. Various assessment tools are available, with life cycle assessment being a commonly employed methodology in the industrial sector. However, its application to infrastructure projects has inherent challenges, primarily due to the complexity associated with inventory management. This complexity has resulted in a limited adoption of LCA within this sector. This research explores the suitability and compatibility of existing tools, methodologies, and databases, while establishing future requirements to adapt LCA and other types of environmental analysis to the life cycle of roads. To achieve this objective, a comprehensive analysis of the scientific and technical literature is conducted in this study. The findings highlight the need for more versatile impact analysis tools, including specialized databases tailored to the specifics of road infrastructure. Such enhancements would facilitate the application of procedures outlined in ISO 14040 and ISO 14044 standards.

Bioinformatic Analysis of Recurrent Genomic Alterations and Corresponding Pathway Alterations in Ewing Sarcoma.

Ewing Sarcoma (ES) is an aggressive, mesenchymal malignancy associated with a poor prognosis in the recurrent or metastatic setting with an estimated overall survival (OS) of <30% at 5 years. ES is characterized by a balanced, reciprocal chromosomal translocation involving the EWSR1 RNA-binding protein and ETS transcription factor gene (EWS-FLI being the most common). Interestingly, murine ES models have failed to produce tumors phenotypically representative of ES. Genomic alterations (GA) in ES are infrequent and may work synergistically with EWS-ETS translocations to promote oncogenesis. Aberrations in fibroblast growth factor receptor (FGFR4), a receptor tyrosine kinase (RTK) have been shown to contribute to carcinogenesis. Mouse embryonic fibroblasts (MEFs) derived from knock-in strain of homologous Fgfr4G385R mice display a transformed phenotype with enhanced TGF-induced mammary carcinogenesis. The association between the FGFRG388R SNV in high-grade soft tissue sarcomas has previously been demonstrated conferring a statistically significant association with poorer OS. How the FGFR4G388R SNV specifically relates to ES has not previously been delineated. To further define the genomic landscape and corresponding pathway alterations in ES, comprehensive genomic profiling (CGP) was performed on the tumors of 189 ES patients. The FGFR4G388R SNV was identified in a significant proportion of the evaluable cases (n = 97, 51%). In line with previous analyses, TP53 (n = 36, 19%), CDK2NA/B (n = 33, 17%), and STAG2 (n = 22, 11.6%) represented the most frequent alterations in our cohort. Co-occurrence of CDK2NA and STAG2 alterations was observed (n = 5, 3%). Notably, we identified a higher proportion of TP53 mutations than previously observed. The most frequent pathway alterations affected MAPK (n = 89, 24% of pathological samples), HRR (n = 75, 25%), Notch1 (n = 69, 23%), Histone/Chromatin remodeling (n = 57, 24%), and PI3K (n = 64, 20%). These findings help to further elucidate the genomic landscape of ES with a novel investigation of the FGFR4G388R SNV revealing frequent aberration.

Altered landscape pattern dominates the declined urban evapotranspiration trend

Urbanization has significantly altered the regional hydrological cycle and thermal environment. However, the response of urban evapotranspiration (ETu) to these altered urban landscape patterns remains unclear. This study proposes a hybrid ETu model that combines physics processes and machine learning to evaluate trends and drivers of ETu across 480 cities in China. The results indicate that the long-term average ETu across the 480 cities is 508 mm, and the average rate of decline in ETu (DRETu) across the 480 cities is 2.19 mm/year. DRETu exhibits a positive correlation with the increasing rate of urban aridity index (AI) and fractional impermeable surface coverage (fi). The decrease in ETu is primarily caused by the altered urban landscape patterns, which include: 1) reductions in urban vegetation and water body areas resulting from urbanization; and 2) the substitution of natural forest land with landscape grasslands in urban areas. We further investigated the correlation between the urban heat island (UHI) effect and ETu and found that the intensified UHI effect is caused by an increased difference in ETu between the main urban area and the suburbs. The results of this study emphasize the significance of constructing water bodies and green infrastructure in the central urban area, as well as restoring natural forests, to enhance the thermal comfort of the urban environment.

Measuring anthropogenic impact of the ox-bow lakes in moribund Ganges deltaic India

Measuring the anthropogenic impact score (AIS) of the ox-bow lakes in order to explore the present situation and future ways of restoration is very necessary, particularly in highly populated areas. The present work targeted to do this considering 68 contributing parameters under eight AIS constituting components like pollution impact score (PIS), habitat alteration impact score (HAIS), hydrological alteration impact score (HYAIS), landscape alteration impact score (LAIS), etc. and tried to explore the major determinants behind. Machine learning (ML) algorithms were applied for computing component level and overall, AIS. A supervised correlation attribute evaluator (CAE) was applied for detecting major determinants.The result revealed out of total 44 major ox-bow lakes 40.90 % to 59.09 % (9.97 km2 to 14.69 km2) were identified as highly impacted both at the component level and overall scale as per the best predicted Random Forest (RF) model. Hydrologically connected lakes were less impacted than isolated ones. Genetically main river (Bhagirathi-Hooghly) left ox-bow lakes are less affected than those of the off-shoot channel. Larger size lakes witnessed less impact than medium and smaller lakes. Pollution, habitat, and hydrological components were found as the most dominant components of AIS. Reclamation, pollution, and eutrophication factors were identified as the dominant factors. AIS is negatively associated with fish yield and positively associated with the livelihood vulnerability of the dependent fishermen community. Since hydrological connectivity is a big issue; maintenance of it could be a good approach to its sustainability.

Edaphic Beetles (Insecta: Coleoptera) in Three Different Land Use Systems in the Eastern Amazon

Objective: The objective of this study was to evaluate edaphic beetles’ abundance, diversity indexes and composition dependence in different land-use systems (LUS) under tropical climate conditions. Method: We surveyed three different LUS such as primary forest fragment (FFP), agroforestry system (SAF) and conventional agricultural cultivation (CAC) in Eastern Amazon. The edaphic beetles were collected using pitfall traps, identified to the family taxonomic level and classified into trophic guilds (carnivore, detritivore, fungivore, and/or herbivore). Results and conclusion: All LUS showed strong dominance by Scarabaeidae and Staphylinidae families. The edaphic beetles community is influenced by the LUS, since the highest rates of abundance, average richness, diversity and evenness were found in the CAC. Edaphic beetles’ composition is dependent to natural vegetation, which accumulated richness is the greatest parameter related to natural vegetation. Research implications: No-tillage cultivation, with homogeneous vegetation formed by decayed plant material from the last culture cycle, can improve and preserve beetles’ detritivore trophic guild. Due to the edaphic beetles’ composition dependence to natural vegetation, is important to preserve forest fragments near altered landscapes to ensure better conditions for this organism’s reestablishment. Originality/value: Edaphic beetles have rarely been studied under different LUS with tropical conditions, particularly in the Eastern Amazon. Comprising these organisms distribution pattern after land-use changes is essential for ecological conservation implications.