Metabolomic Profiles in Jamaican Children With and Without Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, metabolic perturbations associated with ASD, which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls in order to identify specific metabolites that may serve as biomarkers for the disorder. We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica, an age and sex-matched cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and missing data imputation, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child's parish of birth. Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three metabolites were fatty acids, including myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. The amino acid sarcosine exhibited a significant association with ASD. These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.

Phosphoglycerate mutase regulates Treg differentiation through control of serine synthesis and one-carbon metabolism.

The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3PG), the PGAM substrate, to de novo serine synthesis. Blocking de novo serine synthesis from 3PG reversed the effect of PGAM inhibition on Treg polarization, while exogenous serine directly inhibited Treg polarization. Additionally, altering serine levels in vivo with a serine/glycine-free diet increased peripheral Tregs and attenuated autoimmunity in a murine model of multiple sclerosis. Mechanistically, we found that serine limits Treg polarization by contributing to one-carbon metabolism and methylation of Treg-associated genes. Inhibiting one-carbon metabolism increased Treg polarization and suppressive function both in vitro and in vivo in a murine model of autoimmune colitis. Our study identifies a novel physiologic role for PGAM and highlights the metabolic interconnectivity between glycolysis, serine synthesis, one-carbon metabolism, and epigenetic regulation of Treg differentiation and suppressive function.

Metabolomic profiles in Jamaican children with and without autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, the underlying metabolic perturbations associated with ASD which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls. Objective: To elucidate potential metabolomic signatures associated with ASD in children and identify specific metabolites that may serve as biomarkers for the disorder. Methods: We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica (ERAJ-2), which was a 1:1 age (±6 months)-and sex-matched cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and imputation of missing values, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child's parish of birth. Results: Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three of these metabolites were fatty acids, including myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. Additionally, the amino acid sarcosine exhibited a significant association with ASD. Conclusions: These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.

Human intervention caused massive destruction of the second largest mangrove forest, Chakaria Sundarbans, Bangladesh.

Mangroves provide essential ecosystem services including coastal protection by acting as coastal greenbelts; however, human-driven anthropogenic activities altered their existence and ecosystem functions worldwide. In this study, the successive degradation of the second largest mangrove forest, Chakaria Sundarbans situated at the northern Bay of Bengal part of Bangladesh was assessed using remote sensing approaches. A total of five multi-temporal Landsat satellite imageries were collected and used to observe the land use land cover (LULC) changes over the time periods for the years 1972, 1990, 2000, 2010, and 2020. Further, the supervised classification technique with the help of support vector machine (SVM) algorithm in ArcGIS 10.8 was used to process images. Our results revealed a drastic change of Chakaria Sundarbans mangrove forest, that the images of 1972 were comprised of mudflat, waterbody, and mangroves, while the images of 1990, 2000, 2010, and 2020 were classified as waterbody, mangrove, saltpan, and shrimp farm. Most importantly, mangrove forest was the largest covering area a total of 64.2% in 1972, but gradually decreased to 12.7%, 6.4%, 1.9%, and 4.6% for the years 1990, 2000, 2010, and 2020, respectively. Interestingly, the rate of mangrove forest area degradation was similar to the net increase of saltpan and shrimp farms. The kappa coefficients of classified images were 0.83, 0.87, 0.80, 0.87, and 0.91 with the overall accuracy of 88.9%, 90%, 85%, 90%, and 93.3% for the years 1972, 1990, 2000, 2010, and 2020, respectively. By analyzing normalized difference vegetation index (NDVI), soil adjusted vegetation index (SAVI), and transformed difference vegetation index (TDVI), our results validated that green vegetated area was decreased alarmingly with time in this study area. This destruction was mainly related to active human-driven anthropogenic activities, particularly creating embankments for fish farms or salt productions, and cutting for collection of wood as well. Together all, our results provide clear evidence of active anthropogenic stress on coastal ecosystem health by altering mangrove forest to saltpan and shrimp farm saying goodbye to the second largest mangrove forest in one of the coastal areas of the Bay of Bengal, Bangladesh.

P2Y2 purinergic receptor gene deletion protects mice from bacterial endotoxin and sepsis-associated liver injury and mortality.

The liver plays a significant role in regulating a wide range of metabolic, homeostatic, and host-defense functions. However, the impact of liver injury on the host's ability to control bacteremia and morbidity in sepsis is not well understood. Leukocyte recruitment and activation lead to cytokine and chemokine release, which, in turn, trigger hepatocellular injury and elevate nucleotide levels in the extracellular milieu. P2Y2 purinergic receptors, G protein-coupled and activated by extracellular ATP/UTP, are expressed at the cell surface of hepatocytes and nonparenchymal cells. We sought to determine whether P2Y2 purinergic receptor function is necessary for the maladaptive host response to bacterial infection and endotoxin-mediated inflammatory liver injury and mortality in mice. We report that P2Y2 purinergic receptor knockout mice (P2Y2-/-) had attenuated inflammation and liver injury, with improved survival in response to LPS/galactosamine (LPS/GalN; inflammatory liver injury) and cecal ligation and puncture (CLP; polymicrobial sepsis). P2Y2-/- livers had attenuated c-Jun NH2-terminal kinase activation, matrix metallopeptidase-9 expression, and hepatocyte apoptosis in response to LPS/GalN and attenuated inducible nitric oxide synthase and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 protein expression in response to CLP. Implicating liver injury in the disruption of amino acid homeostasis, CLP led to lower serum arginine and higher bacterial load and morbidity in the WT mice, whereas serum arginine levels were comparable to sham-operated controls in P2Y2-/- mice, which had attenuated bacteremia and improved survival. Collectively, our studies highlight the pathophysiological relevance of P2Y2 purinergic receptor function in inflammatory liver injury and dysregulation of systemic amino acid homeostasis with implications for sepsis-associated immune dysfunction and morbidity in mice.NEW & NOTEWORTHY Our studies provide experimental evidence for P2Y2 purinergic receptor-mediated potentiation of inflammatory liver injury, morbidity, and mortality, in two well-established animal models of inflammatory liver injury. Our findings highlight the potential to target P2Y2 purinergic signaling to attenuate the induction of "cytokine storm" and prevent its deleterious consequences on liver function, systemic amino acid homeostasis, host response to bacterial infection, and sepsis-associated morbidity and mortality.

Protein-Protein Interaction Network Mapping by Affinity Purification Cross-Linking Mass Spectrometry (AP-XL-MS) based Proteomics.

Protein-protein interactions (PPIs) are the physical interactions formed among proteins. These interactions are primarily functional, i.e., they arise from specific biomolecular events, and each interaction interface serves a specific purpose. A significant number of methods have been developed for protein interactions in the field of proteomics in the last decade. Advanced mass spectrometry technology significantly contributed to the development of these methods. The rapid advancement of groundbreaking MS technology has greatly aided the mapping of protein interaction from large-data sets comprehensively. This chapter describes the affinity purification (AP) mass spectrometry (MS)-based methods combined with chemical cross-linking (XL) of protein complexes. This chapter includes sample preparation methods involving cell culture, cell treatments with ligands, drugs, and cross-linkers, protein extractions, affinity purification, sodium dodecyl sulfate (SDS) polyacrylamide gel separation, in-solution or in-gel digestion, liquid-chromatography, and mass spectrometry analysis of samples (LC-MS/MS). Application of a cleavable cross-linker, dual cleavable cross-linking technology (DUCCT) in combination with the affinity purification (AP) method has also been described. Methods for data analysis using unmodified and cross-linked peptide analysis are discussed.

Quail Rearing Practices and Potential for Avian Influenza Virus Transmission, Bangladesh.

In 2015, human influenza surveillance identified a human infection with A/H9N2 in Dhaka, Bangladesh with evidence of exposure to a sick quail. We conducted in-depth interviews with household quail caregivers, pet bird retail shop owners, and mobile vendors, key informant interviews with pet bird wholesale shop owners, one group discussion with pet bird retail shop workers and unstructured observations in households, pet bird wholesale and retail markets, and mobile bird vendor's travelling areas to explore quail rearing and selling practices among households, mobile vendors, and retail pet bird and wholesale bird markets in Dhaka. Every day, quail were supplied from 23 districts to two wholesale markets, and then sold to households and restaurants directly, or through bird shops and mobile vendors. All respondents (67) reported keeping quail with other birds in cages, feeding quail, cleaning feeding pots, removing quail faeces, slaughtering sick quail, and discarding dead quail. Children played with quail and assisted in slaughtering of quail. Most respondents (94%) reported rinsing hands with water only after slaughtering and disposing of wastes and dead quail. No personal protective equipment was used during any activities. Frequent unprotected contact with quail and their by-products potentially increased the risk of cross-species avian influenza virus transmission. Avian influenza surveillance in retail pet bird and wholesale bird markets, mobile vendors, and households may identify cases promptly and reduce the risk of virus transmission.

A bibliometric analysis of sustainable development goals (SDGs): a review of progress, challenges, and opportunities.

The Sustainable Development Goals (SDGs) are a global appeal to protect the environment, combat climate change, eradicate poverty, and ensure access to a high quality of life and prosperity for all. The next decade is crucial for determining the planet's direction in ensuring that populations can adapt to climate change. This study aims to investigate the progress, challenges, opportunities, trends, and prospects of the SDGs through a bibliometric analysis from 2015 to 2022, providing insight into the evolution and maturity of scientific research in the field. The Web of Science core collection citation database was used for the bibliometric analysis, which was conducted using VOSviewer and RStudio. We analyzed 12,176 articles written in English to evaluate the present state of progress, as well as the challenges and opportunities surrounding the SDGs. This study utilized a variety of methods to identify research hotspots, including analysis of keywords, productive researchers, and journals. In addition, we conducted a comprehensive literature review by utilizing the Web of Science database. The results show that 31% of SDG-related research productivity originates from the USA, China, and the UK, with an average citation per article of 15.06. A total of 45,345 authors around the world have contributed to the field of SDGs, and collaboration among authors is also quite high. The core research topics include SDGs, climate change, Agenda 2030, the circular economy, poverty, global health, governance, food security, sub-Saharan Africa, the Millennium Development Goals, universal health coverage, indicators, gender, and inequality. The insights gained from this analysis will be valuable for young researchers, practitioners, policymakers, and public officials as they seek to identify patterns and high-quality articles related to SDGs. By advancing our understanding of the subject, this research has the potential to inform and guide future efforts to promote sustainable development. The findings indicate a concentration of research and development on SDGs in developed countries rather than in developing and underdeveloped countries.

Recognizing Zooeyia to Promote Companion Animal Welfare in Urban Bangladesh.

The One Health concept of zooeyia refers to the benefits of companion animals in human health and is gaining global research attention. This exploratory study aimed to understand contemporary experiences and perceptions of the social benefits and challenges of living with a companion animal in urban Bangladesh. Thirty-five qualitative interviews were conducted with companion animal owners (20), animal sellers (10), and livestock service department officers (5) from two major cities in Bangladesh, Dhaka and Khulna. Thematic analysis found that historically, animals had a utilitarian purpose, such as livestock for food and dogs for security. The role and perceptions of companion animals began to change for some around the turn of the century. Today, companion animal caretakers report social, psychological and physical health benefits from integrating companion animals into their lives. They also report that companion animal ownership can contribute to social problems due to the prevailing stigma against companion animals. This is rooted in the continued utilitarian role attached to companion animals by the majority of the Bangladesh population as well as religious-based non-acceptance. As a result, the Animal Welfare Act (2019) is not well implemented, posing a key concern for companion animal welfare. To tackle this, we propose various ways in which the emerging concept of zooeyia can help promote the welfare of companion animals by challenging the stigma associated with them in Bangladesh.

Evolution of cisplatin resistance through coordinated metabolic reprogramming of the cellular reductive state.

BACKGROUND: Cisplatin (CDDP) is a mainstay treatment for advanced head and neck squamous cell carcinomas (HNSCC) despite a high frequency of innate and acquired resistance. We hypothesised that tumours acquire CDDP resistance through an enhanced reductive state dependent on metabolic rewiring. METHODS: To validate this model and understand how an adaptive metabolic programme might be imprinted, we performed an integrated analysis of CDDP-resistant HNSCC clones from multiple genomic backgrounds by whole-exome sequencing, RNA-seq, mass spectrometry, steady state and flux metabolomics. RESULTS: Inactivating KEAP1 mutations or reductions in KEAP1 RNA correlated with Nrf2 activation in CDDP-resistant cells, which functionally contributed to resistance. Proteomics identified elevation of downstream Nrf2 targets and the enrichment of enzymes involved in generation of biomass and reducing equivalents, metabolism of glucose, glutathione, NAD(P), and oxoacids. This was accompanied by biochemical and metabolic evidence of an enhanced reductive state dependent on coordinated glucose and glutamine catabolism, associated with reduced energy production and proliferation, despite normal mitochondrial structure and function. CONCLUSIONS: Our analysis identified coordinated metabolic changes associated with CDDP resistance that may provide new therapeutic avenues through targeting of these convergent pathways.

Quantitative assessment of present and the future potential threat of coastal erosion along the Odisha coast using geospatial tools and statistical techniques.

The eastern coast of India is one of the regions where most of the population resides in urban areas in the low-elevation coastal zone, making it vulnerable to frequent extreme weather events. The objectives of this study are to assess the short- to long-term shoreline changes of the Odisha coast, to understand how anthropogenic influences, and particularly extreme natural events, affect these changes, and to predict shoreline changes for 2050. This study utilized multi-temporal/spectral/spatial resolution satellite images and a digital shoreline analysis (DSAS) tool to appraise the short- (at five/six-year intervals) and long-term (1990-2019) shoreline dynamics along the coastal part of Odisha over the past three decades (1990-2019). The long-term shoreline analysis shows that the mean shoreline change is about 0.67 m/year and highlights that 52.47 % (227.4 km), 34.70 % (150.4 km), and 12.83 % (55.6 km) of the total Odisha coastline exhibit erosion, accretion, and stability, respectively. During the short-term analysis, the 2000-2005 period had the highest percentage of erosion (64.27 %), followed by the 2005-2010 period with an erosional trend of 59.06 %. The 1995-2000 period showed an accretion trend, whereas, during the last period, i.e., 2015-2019, the percentage of transects depicting erosion and accretion was almost similar. In 2050, 55.85 % of the transects are expected to show accretion, while 44.15 % would show erosion or a constant trend. The study identified the hotspots of coastal erosion along delineated study zones by synthesizing data from previous studies as well. The regional analysis of shoreline change along the Odisha coast would not only provide coastal managers with critical information on shoreline dynamics but also draw attention to vulnerable areas linked to shoreline dynamicity along the coast.

Exploring customers' perceptions of food adulteration at bazaars and supermarkets in Dhaka, Bangladesh; a qualitative exploration.

BACKGROUND: Food adulteration is an increasingly recognized global public health problem. In low- and middle-income countries like Bangladesh, adulteration is difficult to detect and respond to. We explored customers' perceptions on food adulteration, perception of risk and connections between information, participant characteristics and patterns of adulterated food concerns that impact risk perception in urban Bangladesh. METHODS: A formative study was conducted in Dhaka, between June and August 2015 at a supermarket and a wet market. We explored community awareness and response to chemical contaminants (adulterants) among participants from a range of socio-economic backgrounds. The team conducted 38 in-depth interviews with 12 customers and 4 staff from a supermarket, and 12 customers and 10 vendors from a wet market. Participants were selected purposively. Audio recorded data were coded based on thematic content and analyzed manually. RESULTS: We asked participants how common foods were likely adulterated, and most gave figures of 70% or more. They reported that foods were adulterated with chemicals or artificial colors, especially fish, milk, and vegetables. The supermarket more commonly sold packaged foods with nutritional and expiry information on the label; and offered convenience in terms of building size, layout, and cleanliness. All customers from the wet market thought that foods were cheaper and fresher than from supermarkets. Supermarket customers expressed greater concern about adulterated foods than wet market customers. Most participants from both markets reported that food adulteration is invisible, adulterated foods cannot be avoided, and have long-term negative health impacts including cancer, diabetes, paralysis, heart attack, and others. Nearly half of customers from both markets were concerned about the poor nutritional value of adulterated food. Participants from both settings expressed the need for access to credible information about adulteration to help choose safe foods. The majority expressed the need for government action against those who are responsible for adulteration. CONCLUSIONS: Food adulteration was considered a major health threat. The government could act on food adulteration prevention if provided credible population-based data on disease burden, a model food sampling and testing protocol, a model for inspections, organizational strengthening and training, example social and behavioral change communications with estimated costs.

Lipopolysaccharide and statin-mediated immune-responsive protein networks revealed in macrophages through affinity purification spacer-arm controlled cross-linking (AP-SPACC) proteomics.

Toll-like receptor 4 (TLR4), a pattern recognition receptor, is activated by lipopolysaccharides (LPS) and induces the MyD88 pathway, which subsequently produces pro-inflammatory cytokines through activation of transcriptional nuclear factor (NF)-κB. Statins have been widely prescribed to reduce cholesterol synthesis for patients with cardiovascular disease. Statins may have pleiotropic effects, which include anti- and pro-inflammatory effects on cells. The molecular mechanism of the sequential influence of LPS and statin on the innate immune system remains unknown. We employed affinity purification-spacer-arm controlled cross-linking (AP-SPACC) MS-based proteomics analysis to identify the LPS- and statin-LPS-responsive proteins and their networks. LPS-stimulated RAW 264.7 macrophage cells singly and combined with the drug statin used in this study. Two chemical cross-linkers with different spacer chain lengths were utilized to stabilize the weak and transient interactors. Proteomic analysis identified 1631 differentially expressed proteins. We identified 151 immune-response proteins through functional enrichment analysis and visualized their interaction networks. Selected candidate protein-coding genes were validated, specifically squamous cell carcinoma antigens recognized by T cells 3, sphingosine-1-phosphate lyase 1, Ras-related protein Rab-35, and tumor protein D52 protein-coding genes through transcript-level expression analysis. The expressions of those genes were significantly increased upon statin treatment and decreased in LPS-stimulated macrophage cells. Therefore, we presumed that the expression changes of genes occurred due to immune response during activation of inflammation. These results highlight the immune-responsive proteins network, providing a new platform for novel investigations and discovering future therapeutic targets for inflammatory diseases.

Assessment of benthic macroinvertebrates as potential bioindicators of anthropogenic disturbance in southeast Bangladesh coast.

Many human activities can greatly influence and alter the health of aquatic ecosystems. In this regard, the quantitative analysis of macroinvertebrates and their relationships with ecological variables is an effective method in environmental monitoring programs. Here, we used the benthic macroinvertebrate community as bioindicators for assessing anthropogenic impacts on coastal waters in southeast Bangladesh. Sediment samples were collected seasonally from three different sites influenced either by mangrove forests, aquaculture activity or sewage input. The indicator value index (IndVal) analysis revealed 23 species of benthic macroinvertebrates as potential bioindicators namely Enigmonia aenigmatica, Mactra chinensis and Pharella javanica of the class Bivalvia; Tubifex tubifex of the class Clitellata; Lithopoma brevispina, Bullia vittata, Pomacea maculata and Umbonium vestiarium of the class Gastropoda; Gammarus roeselii of the class Malacostraca; and Amphicteis gunneri, Amphitrite ornata, Aricidea simplex, Cirratulus cirratus, Heterospio catalinensis, Hypereteone foliosa, Lopadorrhynchus henseni, Neanthes chingrighattensis, Micronephthys oligobranchia, Nephtys hombergii, Nereis jacksoni, Nereis zonata, Polyodontes maxillosus and Stygocapitella subterranean of the class Polychaeta. Their composition across three sites varied significantly (P < 0.05) due to influence of environmental conditions as inferred from redundancy analysis. Polychaeta, Gastropoda and Malacostraca were susceptible to sewage input, while Bivalvia and Clitellata were susceptible to aquaculture effluent. The results of this baseline study suggest that the identified benthic macroinvertebrate species can potentially be used to monitor anthropogenic disturbances in the marine environment.

Associations Between Reported Post-COVID-19 Symptoms and Subjective Well-Being, Israel, July 2021 -April 2022

The impact of individual symptoms reported post-COVID-19 on subjective well-being (SWB) is unknown. We described associations between SWB and selected reported symptoms following SARS-CoV-2 infection. We analysed reported symptoms and subjective well being from 2295 participants (of which 576 reporting previous infection) in an ongoing longitudinal cohort study taking place in Israel. We estimated changes in SWB associated with reported selected symptoms at three follow-up time points (3-6, 6-12, and 12-18 months post infection) among participants reporting previous SARS-CoV-2 infection, adjusted for key demographic variables, using linear regression. Our results suggest that the biggest and most sustained changes in SWB stems from non-specific symptoms (fatigue -7.7 percentage points (pp), confusion/ lack of concentration -10.7 pp, and sleep disorders -11.5pp, p<0.005), whereas the effect of system-specific symptoms, such as musculoskeletal symptoms (weakness in muscles and muscle pain) on SWB, are less profound and more transient. Taking a similar approach for other symptoms and following individuals over time to describe trends in SWB changes attributable to specific symptoms will help understand the post-acute phase of COVID-19 and how it should be defined and better managed.

Identification of Inflammatory Proteomics Networks of Toll-like Receptor 4 through Immunoprecipitation-Based Chemical Cross-Linking Proteomics.

Toll-like receptor 4 (TLR4) is a receptor on an immune cell that can recognize the invasion of bacteria through their attachment with bacterial lipopolysaccharides (LPS). Hence, LPS is a pro-immune response stimulus. On the other hand, statins are lipid-lowering drugs and can also lower immune cell responses. We used human embryonic kidney (HEK 293) cells engineered to express HA-tagged TLR-4 upon treatment with LPS, statin, and both statin and LPS to understand the effect of pro- and anti-inflammatory responses. We performed a monoclonal antibody (mAb) directed co-immunoprecipitation (CO-IP) of HA-tagged TLR4 and its interacting proteins in the HEK 293 extracted proteins. We utilized an ETD cleavable chemical cross-linker to capture weak and transient interactions with TLR4 protein. We tryptic digested immunoprecipitated and cross-linked proteins on beads, followed by liquid chromatography-mass spectrometry (LC-MS/MS) analysis of the peptides. Thus, we utilized the label-free quantitation technique to measure the relative expression of proteins between treated and untreated samples. We identified 712 proteins across treated and untreated samples and performed protein network analysis using Ingenuity Pathway Analysis (IPA) software to reveal their protein networks. After filtering and evaluating protein expression, we identified macrophage myristoylated alanine-rich C kinase substrate (MARCKSL1) and creatine kinase proteins as a potential part of the inflammatory networks of TLR4. The results assumed that MARCKSL1 and creatine kinase proteins might be associated with a statin-induced anti-inflammatory response due to possible interaction with the TLR4.

Boiler ash utilization in the Canadian pulp and paper industry.

Pulp and paper mill biomass boilers generate large quantities of ash in Canada with British Columbia (BC) being the highest ash generating province followed closely by Quebec. Generally, the generated ash is landfilled, particularly in BC, with only a small amount being used beneficially. It is anticipated that the difficulty associated with the management of ash will worsen over time as the industry increases its reliance on green fuel. Thus, there is a strong need to identify beneficial uses of pulp and paper boiler ash for the sake of environmental and economic sustainability. The purpose of this report is to provide the first step in this direction, a review of proposed or implemented uses for coal and hog (or wood) ash around the world. Considering both the properties of the ash and local opportunities, this could be the first step toward screening the applications that may apply to individual mills. Several large-scale practices use ash, such as land application (as a nutrient source or as a liming agent), use in the construction industry (as a replacement for cement or as a fill material), and reclamation of mine sites and stabilization of unpaved forest roads. In some cases, relatively small-scale applications have been used which included uses such as a compost component, agent for pH adjustment of liquid streams and slurries, blasting abrasive, and source of quartz for glass manufacturing to name a few. It is important to note that the chemical nature of both fly and bottom ashes can be quite variable due to the type of wood residues combusted as well as combustion equipment used and must be considered in identifying beneficial applications.

IDH1 p.R132H ctDNA and D-2-hydroxyglutarate as CSF biomarkers in patients with IDH-mutant gliomas.

INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas. METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images. RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 of the 9 samples from patients with IDH-mutant glioma, and IDH1 p.R132H mutation was detected in 5 of the 7 samples. The MAF ranged from 0.3 to 39.95%. Total 2HG level, D-2HG level, and D/L-2HG ratio in CSF were significantly higher in patients with IDH-mutant gliomas than in patients with IDH-wildtype gliomas. D-2HG level and D/L-2HG ratio correlated with total tumor volume in patients with IDH-mutant gliomas but not in patients with IDH-wildtype gliomas. CONCLUSION: Our results suggest that detection of IDH1 p.R132H mutation by ddPCR and increased D-2HG level in CSF may help identify IDH-mutant gliomas. Our results also suggest that D-2HG level and D/L-2HG ratio correlate with tumor volume in patients with IDH-mutant gliomas. Further prospective studies with larger cohorts are needed to validate these findings.

Lipidomic Profiling Identifies a Novel Lipid Signature Associated with Ethnicity-Specific Disparity of Bladder Cancer.

Bladder Cancer (BLCA) is the ninth most frequently diagnosed cancer globally and the sixth most common cancer in the US. African Americans (AA) exhibit half the BLCA incidence compared to European Americans (EA), but they have a 70% higher risk of cancer-related death; unfortunately, this disparity in BLCA mortality remains poorly understood. In this study, we have used an ethnicity-balanced cohort for unbiased lipidomics profiling to study the changes in the lipid fingerprint for AA and EA BLCA tissues collected from similar geographical regions to determine a signature of ethnic-specific alterations. We identified 86 lipids significantly altered between self-reported AA and EA BLCA patients from Augusta University (AU) cohort. The majority of altered lipids belong to phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), ly sophosphatidylcholines (lysoPCs), phosphatidylserines (PSs), and diglycerides (DGs). Interestingly, levels of four lysoPCs (lyso PCs 20:3, lyso PCs 22:1, lyso PCs 22:2, and lyso PCs 26:1) were elevated while, in contrast, the majority of the PCs were reduced in AA BLCA. Significant alterations in long-chain monounsaturated (MonoUN) and polyunsaturated (PolyUN) lipids were also observed between AA and EA BLCA tumor tissues. These first-in-field results implicate ethnic-specific lipid alterations in BLCA.