Site-specific Patterns Research Articles

GlycoPCT: Pressure Cycling Technology-Based Quantitative Glycoproteomics Reveals Distinctive N-Glycosylation in Human Liver Biopsy Samples of Nonalcoholic Fatty Liver Disease.

Protein N-glycosylation is vital in the human liver and influences functions such as lipid metabolism, apoptosis, and inflammation. However, site-specific N-glycosylation patterns and variations in liver biopsy samples between healthy individuals and those with nonalcoholic fatty liver disease (NAFLD) remain incompletely characterized, primarily due to the limitations of current clinical glycoproteomic methods, including a large demand for clinical samples, low efficiency of tissue protein extraction, and a low recovery rate of intact N-glycopeptides (IGPs). To address this issue, we developed GlycoPCT, a quantitative glycoproteomic method based on pressure cycling technology. It enables efficient recovery of IGPs and accurate analysis of trace liver biopsy samples. Our research revealed a total of 4,459 unique IGPs and 361 glycans from 758 glycoproteins. High-mannose type, complex type, fucosylation type, and sialylation type N-glycans were significantly upregulated in the NAFLD group (p < 0.001, t test). Notably, we also identified 182 upregulated IGPs from 67 proteins (p < 0.05, FC > 1.50) and 108 downregulated IGPs from 44 proteins (p < 0.05, FC < 0.67) in the NAFLD group. Furthermore, we highlighted an essential acute phase glycoprotein, alpha-1-acid glycoprotein 1 (A1TA), which is synthesized in the liver and plays a significant role in NAFLD progression. These novel glyco-signatures provide crucial clues for the diagnosis and pathogenesis of NAFLD.

A 'how-to' guide for estimating animal diel activity using hierarchical models.

Animal diel activity patterns can aid understanding of (a) how species behaviourally adapt to anthropogenic and natural disturbances, (b) mechanisms of species co-existence through temporal partitioning, and (c) community or ecosystem effects of diel activity shifts. Activity patterns often vary spatially, a feature ignored by the kernel density estimators (KDEs) currently used for estimating diel activity. Ignoring this source of heterogeneity may lead to biased estimates of uncertainty and misleading conclusions regarding the drivers of diel activity. Thus, there is a need for more flexible statistical approaches for estimating activity patterns and testing hypotheses regarding their biotic and abiotic drivers. We illustrate how trigonometric terms and cyclic cubic splines combined with hierarchical models can provide a valuable alternative to KDEs. Like KDEs, these models accommodate circular data, but they can also account for site-to-site and other sources of variability, correlation amongst repeated measures, and variable sampling effort. They can also more readily quantify and test hypotheses related to the effects of covariates on activity patterns. Through empirical case studies, we illustrate how hierarchical models can quantify changes in activity levels due to seasonality and in response to biotic and abiotic factors (e.g. anthropogenic stressors and co-occurrence). We also describe frequentist and Bayesian approaches for quantifying site-specific (conditional) and population-averaged (marginal) activity patterns. We provide guidelines and tutorials with detailed step-by-step instructions for fitting and interpreting hierarchical models applied to time-stamped data, such as those recorded by camera traps and audio recorders. We conclude that this approach offers a viable, flexible, and effective alternative to KDEs when modelling animal activity patterns.

Site-Specific N-Glycoprofiling of Immunoglobulin G Subtypes from Donkey Milk.

Donkey milk IgG was probed for the site-specific N-glycosylation pattern through RP-UHPLC-MS/MS. The affinity-purified milk IgG was subjected to SDS-PAGE and proteomic analysis, which revealed the presence of subtypes. Multiple N-glycopeptides arising from the predicted donkey IgG1, IgG2, IgG3, IgG5, IgG6, and IgG7 subtypes' heavy-chain constant region were shown to contain glycans at the highly conserved glycosylation site NST in the CH2 domain. Differences in the peptide backbone with the NST site among subtypes generated after trypsin digestion resulted in the evaluation of the subtype-specific glycan pattern. Glycan sequence analysis indicated predominantly biantennary complex types with core fucosylation at the site NST. Interestingly, an additional site NQT in the CH1 domain of the heavy-chain constant region of IgG5 was found to possess mainly sialylated biantennary complex glycans with NeuAc and NeuGc. Structural diversity of glycans was mainly observed in the predicted donkey IgG1, IgG5, and IgG7, whereas IgG2, IgG3, and IgG6 resulted in the glycopeptides that are of low abundance in the analyzed samples. These findings would pave the way for a better understanding of donkey milk functional properties.

Abstract 4141486: Site-Specific Transcriptomic Patterns and Cell Types Associated with Hypertension

Introduction: The biology of early human hypertensive heart disease (HHD) is largely unexplored due to limited cardiac tissue access. Site-specific transcriptomics of human cardiac tissue before development of overt HHD offers a unique vantage to understand the biology of HHD in human cardiac tissue. Hypothesis: We hypothesize that transcriptomic signatures and cell subtype proportions differ in human heart tissue from HTN donors compared to normotensive (NTN) donors in a site-specific manner. Methods: We performed bulk RNA-seq on rRNA-depleted libraries from left (LV) and right (RV) mid-ventricular-wall tissue (average depth 114 million reads/sample) collected postmortem from HTN (n=3, 67% Black/Latinx) and NTN (n=2, 50% Black/Latinx) donors. We performed single-nucleus RNA-seq (snRNA-Seq) on cardiac tissue from the same donors (average of 4,062 LV nuclei). Differential gene expression, lineage identification, and Gene Set Enrichment Analysis (GSEA) were performed with publicly available software. Results: All donors were female with matched postmortem intervals (time from death to tissue preservation; HTN 19±9 hours, NTN 18±6 hours). HTN donors were older (65±7 years) than NTN donors (36±16 years). A total of 416 genes were associated with HTN (Wald test, FDR q &lt;0.05) across both ventricles (correcting for site). When tested separately, 72 (LV) or 83 (RV) genes were associated with HTN (FDR q &lt;0.05), with 13 common genes, indicating site-specific differences. GSEA of genes ranked by Wald statistic computed across both ventricles showed that transcripts involved in single-stranded DNA helicase activity, branched-chain amino acid catabolism, and NAD-dependent deacetylase activity were coordinately associated with HTN (FDR q &lt;0.05). snRNA-seq revealed 9 cell types in these samples, including immune cells and chamber-specific cardiomyocytes (CMs) with higher proportions of LV CMs and lymphocytes associated with HTN compared to NTN. MYH6 and MYL7 expression was unchanged with respect to HTN by RNA-seq but lower in LV HTN CMs compared to NTN by snRNA-seq, suggesting dysregulation of contractile programming in HTN LV CMs. Conclusion: HTN is associated with altered cardiomyocyte/lymphocyte ratios, and site-specific differential expression of cardiac contractile elements. Further study is required to validate these findings with additional samples and elucidate mechanisms driving transcriptional program differences in the hypertensive human heart.

Insights into the seasonal variation, distribution, composition and dynamics of microplastics in the Ganga River ecosystem of Varanasi City, Uttar Pradesh, India.

The current study explores the seasonal dynamics of microplastic (MP) pollution in the Ganga River of Varanasi City, Uttar Pradesh, India, focusing on water and sediment samples collected during pre-monsoon and post-monsoon periods. The analysis shows significant variations in MP occurrence, shape dynamics, color distribution, and size composition across diverse sampling sites. During the pre-monsoon season, MP concentrations ranged from 17 to 36 particles/L in water samples and 160 to 312 particles/kg in sediment, indicating a moderate to high level of contamination. Post-monsoon sampling showed higher MP concentrations at most sites, indicating the influence of seasonal hydrological changes on MP distribution. Shifts in MP shape dynamics were observed between seasons, with films, foams, fragments, and filaments showing variable distributions. Similarly, color variations in MPs exhibited site-specific patterns, with white, brown, blue, and other colors being predominant. These findings highlight the diverse sources and compositions of MPs in the river ecosystem, highlighting the complexity of MP pollution dynamics. Polymer-type distributions further elucidated the composition of MPs, with notable contributions from polyethylene terephthalate, rayon, polyester, and polyvinyl chloride. PCA analysis revealed significant shifts in particle size and shape distribution between pre-monsoon and post-monsoon periods in both water and sediment samples, with post-monsoon samples showing an increase in larger particles and filaments. These changes highlighted key factors driving the variance in microplastic contamination across different sites. The prevalence of these polymers features diverse sources of MP pollution, including textiles, packaging materials, and industrial waste. Ongoing monitoring and research are crucial to understanding its sources, distribution, and impact on river ecosystems, essential for protecting aquatic biodiversity and human health.

Long-term surveys of ungulates' effects on tree and shrub species in mountainous forests -outcomes and potential limits.

Ungulate herbivory might induce different effects on the diversity and growth of trees and shrubs. The density, distribution, and the species of ungulates as well as plant communities' composition and other factors determine whether ungulate herbivory promotes or limits plants' diversity and growth. The impacts of ungulates on woody plants are commonly surveyed with exclosure-control approaches. In practice, such surveys frequently only cover short periods of time, addressing immediate management needs. Long-term surveys, documenting lasting effects of ungulate herbivory, are highly needed, but still rare. However, the general transferability of outcomes of long-term surveys might be limited due to different disturbing factors. This study addresses two basic aspects of long-term monitoring in mountainous forests, based on a unique 30-year data set: (1) Possible long-term effects of herbivores on forest vegetation (e.g., species/structural diversity of woody plants) and (2) potential differences between short-term and long-term surveys in terms of height growth patterns. In our study, diversity of woody plant species showed great variability with no significant impact of ungulate herbivory. The presence of ungulates had a significantly negative effect on the vertical structural diversity and growth of trees. Due to the slower growth on control plots, it took trees longer to reach a 160 cm height-threshold with their terminal shoots than on exclosure plots. Our long-term control-exclosure data set indicated that long-term survey data indeed might differ from growth patterns represented by short-term surveys. This can be induced by several factors, like site-specific growth patterns of trees, occurrences of natural abiotic disturbances that influence the functional life of exclosures, and others.

Maternal e-cigarette exposure alters DNA methylome, site-specific CpG and CH methylation, and transcriptomic signatures in the neonatal brain

Maternal use of e-cigarette (e-cig) aerosols poses significant risks to fetal brain development, potentially increasing susceptibility to neurodevelopmental disorders in later life. However, the underlying mechanisms remain incompletely understood. This study aimed to understand the effects of fetal e-cig exposure on DNA methylome and transcriptomic changes in the neonatal brain. Pregnant rats were exposed to e-cig aerosols, and neonatal brains (5 males and 5 females/group) from both control and e-cig-exposed groups were used for experimental analysis. Results indicated that prenatal e-cig exposure altered site-specific DNA methylation patterns at both CpG and CH (non-CpG) sites, predominantly in intergenic and intronic regions, with sex dimorphism in methylation and gene expression changes. Gene ontology analysis revealed that e-cig exposure not only affected neuron projection development and axonogenesis but also altered pathways related to neurodegeneration and long-term depression. These findings provide novel insights into the dynamic changes of CpG and CH methylation induced by e-cig exposure, underscoring the susceptibility of the developing brain to maternal e-cig exposure and its potential implications for developmental disorders and neurodegenerative diseases later in life.

Epigenomic and Transcriptomic Profiling of Solitary Fibrous Tumors Identifies Site-Specific Patterns and Candidate Genes Regulated by DNA Methylation

A solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can arise at any anatomical site and is characterized by recurrent NAB2::STAT6 fusions and metastatic progression in 10% to 30%. The cell of origin has not been identified. Despite some progress in understanding the contribution of heterogeneous fusion types and secondary mutations to SFT biology, epigenetic alterations in extrameningeal SFT remain largely unexplored, and most sarcoma research to date has focused on the use of methylation profiling for tumor classification. We interrogated genome-wide DNA methylation in 79 SFTs to identify informative epigenetic changes. RNA-seq data from targeted panels and data from the Cancer Genome Atlas (TCGA) were used for orthogonal validation of selected findings. In unsupervised clustering analysis, the top 500 most variable cytosine-guanine sites segregated SFTs by primary anatomical site. Differentially methylated genes associated with the primary SFT site included EGFR; TBX15; multiple HOX genes; and their cofactors EBF1, EBF3, and PBX1; as well as RUNX1 and MEIS1. Of the 20 DMGs interrogated on the RNA-seq panel, 12 were significantly differentially expressed according to site. However, except TBX15, most of these also showed differential expression according to NAB2::STAT6 fusion type, suggesting that the fusion oncogene contributes to the transcriptional regulation of these genes. Transcriptomic data confirmed an inverse correlation between gene methylation and the expression of TBX15 in both SFT and TCGA sarcomas. TBX15 also showed differential mRNA expression and 5′ UTR methylation between tumors in different anatomical sites in TCGA data. In all analyses, TBX15 methylation and mRNA expression retained the strongest association with tissue of origin in SFT and other sarcomas, suggesting a possible marker to distinguish metastatic tumors from new primaries without genomic profiling. Epigenetic signatures may further help to identify SFT progenitor cells at different anatomical sites.

Dynamic interplay of soil parameters and CO2 sequestration in Solanku-runi Freshwater Pond Wetland, Tamil Nadu, India

This study investigates the dynamic interplay between soil temperature, pH levels, and CO2 sequestration across ten sample sites over a four-month periods from January to April 2018 in Solankuruni freshwater pond wetland in Madurai District, Tamil Nadu, India. The soil temperature fluctuations, ranging from 31°C to 44°C, reveal distinct site-specific patterns, with sample site six consistently exhibiting the highest temperatures. Soil temperature exhibited notable variations, influenced by factors such as soil composition, and microclimate variations. Regarding pH level, the range between 6.23 to 8.1 display variability influenced by factors like soil composition and anthropogenic influences, study site five consistently leading in pH levels. Soil CO2 sequestration varying from 1517.857 g/m² to 3357.143 g/m², highlight the influence of soil microbial activity, vegetation cover, and soil moisture content, ninth site consistently showing the highest sequestration rates. The findings reveal substantial variations in factors such as soil composition, vegetation type, microclimate, and anthropogenic activities, prominence the intricate nature of soil dynamics. These results stress the importance of understanding the interconnections among soil properties to create effective climate change mitigation strategies. Moreover, the research provides valuable understanding of the intricate connections between soil properties, emphasizing the necessity for region-specific studies to inform comprehensive environmental policies. Understanding these dynamic soil processes is crucial for advancing sustainable land management practices and boosting soil carbon sequestration in wetland ecosystems.

Trace metals in coastal marine sediments: Natural and anthropogenic sources, correlation matrices, and proxy potentials

Rapidly spreading industrialization since the 19th century has led to a drastic increase in trace metal deposition in coastal sediments. Provided that these trace metals have remained relatively immobile after deposition, their sedimentary enrichments can serve as records of local–regional pollution histories. Factors controlling this proxy potential include trace metal geochemistry (carrier-, and host phase affinity), and depositional environmental factors (redox variability, particulate shuttling, organic matter loading, bathymetry). Yet, the relative importance and interactions between these controls are still poorly understood, hampering the reliable use of trace metal-based environmental proxies. By summarizing nine site-specific correlation matrices of 16 metal (loid) s (Pb, Cd, Cu, Zn, Sb, Sn, Ni, As, Tl, V, Mo, U, Re, Fe, Mn, Al), total organic C, and S contents in short sediment cores into a single meta-matrix, we test a novel approach for quickly detecting common and contrasting trace metal enrichment patterns across different study locations. Our meta-matrix shows two trace metal groups, within which positive correlations of e.g., Pb, Cd, Zn, Cu, Sb suggest a primary “anthropogenically sourced” (group I) control, whereas known “redox-sensitive” (group II) trace metals (Mo, U, Re) are characterized by fewer positive correlations. However, some group I metals (Cd, Zn, Cu, Sb) also covary with group II metals, inferring that redox variability may obscure primary anthropogenic signals; Sb even shows advantages over Mo and U under oxic conditions. As a more robust pollution indicator we identified Pb; yet for reconstructing historical Pb atmospheric pollution signals (1970s Pb peak), it is crucial to consider the distance from shore. In near-shore environments, local (fluvial) pollution signals may overprint large-scale (atmospheric) signals. Our findings demonstrate that combining site-specific sedimentary correlation and distribution patterns with a meta-matrix considerably aids the understanding of trace metal sequestration in different coastal sedimentary environments, which thereby improves trace metal proxy reliability.

Performance of mussel Mytilus galloprovincialis under variable environmental conditions and anthropogenic pressure: A survey of two distinct farming sites in the Adriatic Sea

Changes in natural conditions and anthropogenic pollutants, alone or in combination, pose a significant challenge to coastal bivalve populations. The susceptibility of economically important bivalves to potential stressors in their farming environment has not been sufficiently investigated, despite the increase in anthropogenic pressure along the coast and the remarkable warming of seawater in recent years. Thus, the aim of this study was to evaluate the performance of mussel (Mytilus galloprovincialis) from two important farming sites in the eastern Adriatic, namely Mali Ston Bay (MSB) and Lim Bay (LB), in relation to variations of seawater parameters, reproductive cycle dynamics and tissue content of potentially harmful pollutants. The complex seasonal and site-specific patterns of chemical pollutants were determined, with tissue levels of metals, As, PAHs and PCBs largely comparable to those previously reported for the Mediterranean region. Concentrations of organochlorinated pesticides were below the level of detection. Significantly higher Cd, As and Hg concentrations were detected in the tissues of the MSB mussels. The reproductive cycle was clearly associated with the bioaccumulation of pollutants. All biochemical response parameters varied to some extent across seasons and/or between farming sites. A very pronounced seasonality was recorded for acetylcholinesterase and glutathione S-transferase activity at both sites. Metallothionein concentration and superoxide dismutase activity were generally steady throughout the study period. The most striking difference between the two sites was recorded for lipid peroxides concentrations which were predominantly significantly higher in the MSB mussels, indicating expressed pro-oxidant conditions at this site. In particular, significant correlations were found between lipid peroxides and the potentially toxic metals (Cd, As, Hg) accumulated in the mussel tissue. Data reported here are valuable as baseline information for further studies related to stress in farmed bivalves caused by oscillations of environmental factors and increasing anthropogenic pressure along the coastline.

Isotope hydrology of the intermontane Elk Valley, British Columbia: an assessment of water resources around coal mining operations

ABSTRACT This study aimed to synthesise and interpret stable isotopic data (δ 2H and δ 18O) from various sources to understand the isotope hydrology around coal mine operations in Elk Valley, B.C., Canada. The data, including precipitation, groundwaters, seeps, and mine rock drains, were used to construct a local meteoric water line (LMWL) for the Elk Valley, evaluate the spatiotemporal isotopic composition of its groundwater, and assess mine seepage and mine rock drain discharge. The study revealed a robust LMWL relation (δ 2H = 7.4 ± 0.2 · δ 18O – 4.3 ± 4.1). The groundwater and seep data indicated a winter season bias and a north–south latitudinal gradient, suggesting rapid near-surface groundwater flow without significant post-precipitation evaporation. Porewater isotope samples from unsaturated mine rock piles (MRPs) showed site-specific evaporation patterns, potentially due to convective air flows or exothermic sulphide oxidation. This research revealed the influence of groundwater and meltwater on rock drain discharge. Based on evaporative mass balance calculations, MRPs seasonally contributed ca. 5 %(December base flow) and 22 % (snowmelt) to drain discharge. The findings underscore the value of stable isotope data collections in the Elk Valley to help better define and quantify the hydrology–hydrogeology, including a better understanding of evaporative conditions in MRPs.

Localization and segmentation of atomic columns in supported nanoparticles for fast scanning transmission electron microscopy

To accurately capture the dynamic behavior of small nanoparticles in scanning transmission electron microscopy, high-quality data and advanced data processing is needed. The fast scan rate required to observe structural dynamics inherently leads to very noisy data where machine learning tools are essential for unbiased analysis. In this study, we develop a workflow based on two U-Net architectures to automatically localize and classify atomic columns at particle-support interfaces. The model is trained on non-physical image simulations, achieves sub-pixel localization precision, high classification accuracy, and generalizes well to experimental data. We test our model on both in situ and ex situ experimental time series recorded at 5 frames per second of small Pt nanoparticles supported on CeO2(111). The processed movies show sub-second dynamics of the nanoparticles and reveal site-specific movement patterns of individual atomic columns.

Site specific binding pattern of benzodiazepines with GABAA receptor and related impact on their activities in the human body: An in silico method based study

Despite of being the drugs of the same therapeutic class (Benzodiazepines), each of them shows different actions prominently. It is commonly seen that Bromazepam, Clonazepam, and, Alprazolam are prescribed for the treatment of anxiety disorders, panic disorders, and phobias. On the other hand, Midazolam, Temazepam, Flurazepam, and Nitrazepam are indicated for the treatment of insomnia and Lorazepam is considered as a drug having anticonvulsant effects. As the mechanism of action is the same, there should be some differences in the binding patterns with the proteins that create differences in their impacts on the body. A deep screening of the binding patterns of the available Benzodiazepines in the market to the GABAA receptor will be beneficial to find out the responsible amino acids for being accountable for showing any specific action. This reveal will help design new molecules with the highest beneficial effect and lowest toxicity in the body. The in silico method provides the initial level of understanding regarding the binding patterns, performing in vitro and in vivo experiments will be more specific to claim the benefits of newly designed drugs.

Spatial patterns of organic matter content in the surface soil of the salt marshes of the Venice Lagoon (Italy)

Abstract. Salt marshes are crucial eco-geomorphic features of tidal environments as they provide important ecological functions and deliver a wide range of ecosystem services. Being controlled by the interplay between hydrodynamics, geomorphology, and vegetation, the contribution of both organic matter (OM) and inorganic sediments drives salt marsh vertical accretion. This allows marshes to keep pace with relative sea level rise and likewise capture and store carbon, making them valuable allies in climate mitigation strategies. Thus, soil organic matter (SOM), i.e. the organic component of the soil, plays a key role within salt marsh environments, directly contributing to soil formation and supporting carbon storage. This study aims at inspecting spatial patterns of OM in surface salt marsh soils (top 20 cm), providing further insights into the physical and biological factors driving OM dynamics that affect salt marsh survival and carbon sink potential. Our results reveal two scales of variations in SOM content in marsh environments. At the marsh scale, OM variability is influenced by the interplay between surface elevation and changes in sediment supply linked with the distance from the marsh edge. At the system scale, OM content distribution is dominated by the gradient generated by marine and fluvial influence. The observed variations in SOM are explained by the combination of inorganic and organic input, preservation conditions, and sediment grain size. Our results highlight the importance of marshes as carbon sink environments, further emphasising that environmental conditions within a tidal system may generate strongly variable and site-specific carbon accumulation patterns, enhancing blue carbon assessment complexity.

The impact of metastatic sites on survival Rates and predictors of extended survival in patients with metastatic pancreatic cancer

Background objectivesThe aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value. MethodsWe examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016–2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen's linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression. ResultsMedian overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001). ConclusionWhile synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies.

Optimizing wind farm layout for enhanced electricity extraction using a new hybrid PSO-ANN method

With the growing need for renewable energy, wind farms are playing an important role in generating clean power from wind resources. The best wind turbine architecture in a wind farm has a major influence on the energy extraction efficiency. This paper describes a unique strategy for optimizing wind turbine locations on a wind farm that combines the capabilities of particle swarm optimization (PSO) and artificial neural networks (ANNs). The PSO method was used to explore the solution space and develop preliminary turbine layouts, and the ANN model was used to fine- tune the placements based on the predicted energy generation. The proposed hybrid technique seeks to increase energy output while considering site-specific wind patterns and topographical limits. The efficacy and superiority of the hybrid PSO-ANN methodology are proved through comprehensive simulations and comparisons with existing approaches, giving exciting prospects for developing more efficient and sustainable wind farms. The integration of ANNs and PSO in our methodology is of paramount importance because it leverages the complementary strengths of both techniques. Furthermore, this novel methodology harnesses historical data through ANNs to identify optimal turbine positions that align with the wind speed and direction and enhance energy extraction efficiency. A notable increase in power generation is observed across various scenarios. The percentage increase in the power generation ranged from approximately 7.7% to 11.1%. Owing to its versatility and adaptability to site-specific conditions, the hybrid model offers promising prospects for advancing the field of wind farm layout optimization and contributing to a greener and more sustainable energy future.

Meta-analysis of mutational site-specificity and concordance/discordance characteristics of myeloid sarcoma.

6583 Background: Myeloid sarcoma (MS) is an atypical, extramedullary manifestation of acute myeloid leukemia. Next-generation sequencing (NGS) studies have explored mutational profiles of MS tumor sites and bone marrow (BM) samples. However, site-specific molecular patterns and mutational concordance/discordance between MS sites and BM remain unclear. Methods: Relevant studies about MS retrieved from a Pubmed search (1999-2023) with information about MS site involvement and NGS data were included. With R software, a meta-analysis (MA) of descriptive data, MS tumor site, mutations, and mutational concordance/discordance was performed to obtain pooled prevalence estimates using the Freeman-Tukey double arcsine transformation, inverse variance, and random effects model. MA of median age was pooled using the methods of McGrath et al. (2023). Meta-regression (MR) was performed with mixed-effects model. Chi-square test was used for statistical analysis of categorical variables. Results: 87 patients with MS from 10 studies were identified. Median age was 53 years (95% confidence interval [CI]: 48-56), and MS was more common in males (pooled estimate of 67%, 95% CI: 54.8-78.5). Skin was the most common site involved in MS with random effects pooled estimate of prevalence of 39.4% (95% CI: 20.8-59.3), followed by lymph node (10.1%, 95% CI: 1.8-21.8), bone (5%, 95% CI: 0.2-13.3), and soft tissue (2.4%, 95% CI: 0-9.5). Pooled estimates of most common mutated genes were NPM1 (20.3%, 95% CI: 6.2-38), FLT3 (18.3%, 95% CI: 5.5-34.6), TP53 (8.4%, 95% CI: 1.8-17.7), NRAS(6.6%, 95% CI: 0.9-15.4), and IDH2 (4.3% 95% CI: 0-13.4). NPM1 (13/34), FLT3 (7/34), and IDH2 (6/28) were enriched in cutaneous MS. KIT was exclusively enriched in non-cutaneous MS (8/53) compared to cutaneous MS (0/34) (p = 0.017). Although the prevalence of small bowel MS was low (n = 3), FLT3 was mutated in all cases (p &lt; 0.01). Comparing MS tumor site to BM, pooled prevalence of mutation concordance was similar to discordance (49.8% [95% CI: 34.4-65.1] and 50.2% [95% CI: 34.9-65.6], respectively). Most common concordant mutations were FLT3 (5/28) and NRAS (5/28). NPM1 and FLT3 were most common discordant mutations and enriched in MS tumor sites (p &lt; 0.01 and p &lt; 0.05, respectively). NPM1 was a discordant mutation in MS tumor site only. Univariate MR of cutaneous MS found no significant influence from male sex and mutational concordance/discordance. Multivariate MR showed significant interaction with males and mutational discordance toward cutaneous MS (p &lt; 0.01). Conclusions: Our meta-analysis highlights potential site-specific and mutational disparities in MS. Knowledge about such differences may allow the use of targeted therapies against different molecular aberrations, emphasizing the need to sequence both BM and MS sites. Findings suggesting interaction of male sex and mutational discordance in cutaneous MS needs further validation.

Characterisation and comparison site-specific N-glycosylation of whey proteins from donkey and human colostrum and mature milk using glycoproteomics

Although the composition of donkey milk is similar to that of human milk, systematic comparisons of the site-specific N-glycosylation patterns of their whey proteins are lacking. In this study, hydrophilic interaction chromatography-based enrichment of intact N-glycopeptides, coupled with a site-specific glycoproteomics strategy, was used to systematically characterise whey N-glycoproteins in donkey colostrum (DC), donkey mature milk (DM), human colostrum (HC), and human mature milk (HM) for the first time. We identified 628, 347, 868, and 425 site-specific N-glycans mapped to 135, 67, 113, and 60 glycoproteins in DC, DM, HC, and HM, respectively. Bioinformatic analysis revealed the potential biological effects of N-glycosylation modifications on the whey proteins themselves. Our findings elucidated the composition of donkey and human milk whey N-glycoproteins and their potential structure-activity relationships and provided guidance for the production of specific functional donkey milk products and the development of donkey milk-based infant formulas.

Distinct Gastrointestinal and Reproductive Microbial Patterns in Female Holobiont of Infertility.

The microbiota is in symbiosis with the human body as a holobiont. Infertility conditions affect the female reproductive tract (FRT) and its resident microbiota. However, a disturbance in homeostasis could influence the FRT and other distal body sites, such as the gastrointestinal tract (GIT). We included 21 patients with endometriosis and other infertility-associated diseases with clinical profiles and biological samples from the FRT (endometrium, endometrial fluid, and vagina), and GIT samples (oral and feces). We performed a 16S rRNA analysis of site-specific microbial communities and estimated diversity metrics. The study found body site-specific microbial patterns in the FRT-GIT. In both study groups, Lactobacillus was the most shared Amplicon Sequence Variant (ASV), a precise identifier of microbial sequences, between endometrial and vagina samples. However, shared Gardnerella and Enterobacteriaceae ASVs were linked to other conditions but not endometriosis. Remarkably, Haemophilus was a specific GIT-shared taxon in endometriosis cases. In conclusion, infertility influences distinctly the FRT and GIT microbiomes, with endometriosis showing unique microbial characteristics. We proposed the concept of 'female holobiont' as a community that comprises the host and microbes that must maintain overall homeostasis across all body sites to ensure a woman's health. Insights into these microbial patterns not only advance our understanding of the pathophysiology of infertility but also open new avenues for developing microbe-based therapeutic interventions aimed at restoring microbial balance, thereby enhancing fertility prospects.