Microbial nitrogen bubble formation in porous media.

Microbially induced nitrogen (N2) gas bubbles can desaturate subsurface areas and thus have been considered as an alternative ground improvement technique for mitigating soil liquefaction potential caused by earthquakes. However, the detailed mechanisms of subsurface N2 bubbles are not well understood and remain a subject of ongoing research. In this study, a transparent microfluidic device was utilized to mimic biological N2 gas bubble formation by nitrate-reducing bacteria and to visually characterize the entire process. During N2 gas formation, a limited number of bubble nucleation sites were identified, which gradually expanded upward through the preferential pore channels. N2 gas bubbles tended to create interconnected gas pockets rather than existing as evenly distributed small gas cavities. The degree of water saturation gradually reduced over a week as the bubbles were produced. The gas ganglia repeatedly grew until they reached the top boundary, which triggered a drastic expulsion of bubbles by ebullition. Despite fluctuations in saturation level, the residual saturation was maintained at around 73 %. Comparative experimental case studies of CO2 gas bubble formation were conducted to identify contrasting gas formation mechanisms. CO2 gas bubbles were generated via the abiotic decompression of a supersaturated CO2 solution under two distinct rates of pressure reduction. Rapid CO2 bubble formation led to uniform nucleation and 41 % residual saturation, while slower formation yielded 35 % due to stable liquid displacement by the gas front. This study highlights the potential of the microfluidic device as an experimental tool for visualizing subsurface gas formation mechanisms. The insights gained could further enhance and optimize geotechnical applications involving gas formation in highly saturated soils.

Synonymous variant at the terminal nucleotide in exon 3 of F7 causes abnormal splicing: A case report.

BACKGROUND: Synonymous variants are non-pathogenic due to non-substitution of amino acids. However, synonymous exonic terminal nucleotide substitutions may affect splicing. Splicing variants are easily analyzed at RNA level for genes expressed in blood cells. Minigene analysis provides another method for splicing variant analysis of genes that are poorly or not expressed in peripheral blood. METHODS: Whole exome sequencing was performed to screen for potential pathogenic mutations in the proband, which were validated within the family by Sanger sequencing. The pathogenicity of the synonymous mutation was analyzed using the minigene technology. RESULTS: The proband harbored the compound heterogeneous variants c. [291G >A; 572-50C >T] and c.681 + 1G >T in F7, of which the synonymous variant c.291G >A was located at the terminal position of exon 3. Minigene analysis revealed exon3 skipping due to this mutation, which may have subsequently affected protein sequence, structure, and function. CONCLUSION: Our finding confirmed the pathogenicity of c.291G >A, thus extending the pathogenic mutation spectrum of F7, and providing insights for effective reproductive counseling.

Post-implantation analysis of genomic variations in the progeny from developing fetus to birth.

The analysis of genomic variations in offspring after implantation has been infrequently studied. In this study, we aim to investigate the extent of de novo mutations in humans from developing fetus to birth. Using high-depth whole-genome sequencing, 443 parent-offspring trios were studied to compare the results of de novo mutations (DNMs) between different groups. The focus was on fetuses and newborns, with DNA samples obtained from the families' blood and the aspirated embryonic tissues subjected to deep sequencing. It was observed that the average number of total DNMs in the newborns group was 56.26 (54.17-58.35), which appeared to be lower than that the multifetal reduction group, which was 76.05 (69.70-82.40) (F = 2.42, P = 0.12). However, after adjusting for parental age and maternal pre-pregnancy body mass index (BMI), significant differences were found between the two groups. The analysis was further divided into single nucleotide variants (SNVs) and insertion/deletion of a small number of bases (indels), and it was discovered that the average number of de novo SNVs associated with the multifetal reduction group and the newborn group was 49.89 (45.59-54.20) and 51.09 (49.22-52.96), respectively. No significant differences were noted between the groups (F = 1.01, P = 0.32). However, a significant difference was observed for de novo indels, with a higher average number found in the multifetal reduction group compared to the newborn group (F = 194.17, P < 0.001). The average number of de novo indels among the multifetal reduction group and the newborn group was 26.26 (23.27-29.05) and 5.17 (4.82-5.52), respectively. To conclude, it has been observed that the quantity of de novo indels in the newborns experiences a significant decrease when compared to that in the aspirated embryonic tissues (7-9 weeks). This phenomenon is evident across all genomic regions, highlighting the adverse effects of de novo indels on the fetus and emphasizing the significance of embryonic implantation and intrauterine growth in human genetic selection mechanisms.

Can Artificial Intelligence Chatbots Improve Mental Health?: A Scoping Review.

BACKGROUND AND OBJECTIVES: Mental health disorders, including anxiety and depression, are the leading causes of global health-related burden and have increased dramatically since the 1990s. Delivering mental healthcare using artificial intelligence chatbots may be one option for closing the gaps in mental healthcare access. The overall aim of this scoping review was to describe the use, efficacy, and advantages/disadvantages of using an artificial intelligence chatbot for mental healthcare (stress, anxiety, depression). METHODS: PubMed, PsycINFO, CINAHL, and Web of Science databases were searched. When possible, Medical Subject Headings terms were searched in combination with keywords. Two independent reviewers reviewed a total of 5768 abstracts. RESULTS: Fifty-four articles were chosen for further review, with 10 articles included in the final analysis. Regarding quality assessment, the overall quality of the evidence was lower than expected. Overall, most studies showed positive trends in improving anxiety, stress, and depression. DISCUSSION: Overall, using an artificial intelligence chatbot for mental health has some promising effects. However, many studies were done using rudimentary versions of artificial intelligence chatbots. In addition, lack of guardrails and privacy issues were identified. More research is needed to determine the effectiveness of artificial intelligence chatbots and to describe undesirable effects.

Emerging trends and hotspots in cervical intraepithelial neoplasia research from 2013 to 2023: A bibliometric analysis.

Background: Cervical intraepithelial neoplasia (CIN) encompasses a range of cervical lesions that are closely linked to cervical invasive carcinoma. Early detection and timely treatment of CIN are crucial for preventing the progression of the disease. However, no bibliometric analysis has been conducted in this area. This research aimed to employ bibliometric analysis to summarize the current research hotspots and estimate future research trends in the CIN field. Methods: Publications related to CIN (2013-2023) were retrieved from the Science-Citation-Index-Expanded-of-Web-of-Science-Core-Collection. CiteSpace, VOSviewer, and the bibliometric-Online-Analysis-Platform-of-Literature-Metrology were employed to analyze the yearly research output, collaborating institutions or countries, leading researchers, principal journals, co-referenced sources, and emerging keywords. Results: In total, 4677 articles on CIN that were published from 2013 to 2023 and met our criteria were extracted. Major publishing platforms were predominantly USA until 2017 when China emerged as the leading source of publications about CIN. The USA was the leading nation in international collaborations. The National-Cancer-Institute (NCI) was the institution with the most publications. Schiffman Mark produced the highest number of articles, with a total of 92. Ten major clusters were identified through co-cited keyword clustering, including prevalence, human papillomavirus, DNA methylation, p16, methylation, conization, HPV genotyping tests (VALGENT), deep learning, vaginal microbiome, and immunohistochemistry. Keyword burst analysis showed that photodynamic therapy and deep learning emerged as prominent research focal points with significant impact in resent three years. Conclusion: Global publications on CIN research showed a relatively stable trend over the past eleven years. Current research hotspots are deep learning and photodynamic therapy. This research offered organized data and insightful guidance for future studies, which may help better prevent, screen, and treat CIN.

Injectable Oxygen-Carrying Microsphere Hydrogel for Dynamic Regulation of Redox Microenvironment of Wounds.

The delayed healing of infected wounds can be attributed to the increased production of reactive oxygen species (ROS) and consequent damages to vascellum and tissue, resulting in a hypoxic wound environment that further exacerbates inflammation. Current clinical treatments including hyperbaric oxygen therapy and antibiotic treatment fail to provide sustained oxygenation and drug-free resistance to infection. To propose a dynamic oxygen regulation strategy, this study develops a composite hydrogel with ROS-scavenging system and oxygen-releasing microspheres in the wound dressing. The hydrogel itself reduces cellular damage by removing ROS derived from immune cells. Simultaneously, the sustained release of oxygen from microspheres improves cell survival and migration in hypoxic environments, promoting angiogenesis and collagen regeneration. The combination of ROS scavenging and oxygenation enables the wound dressing to achieve drug-free anti-infection through activating immune modulation, inhibiting the secretion of pro-inflammatory cytokines interleukin-6, and promoting tissue regeneration in both acute and infected wounds of rat skins. Thus, the composite hydrogel dressing proposed in this work shows great potential for dynamic redox regulation of infected wounds and accelerates wound healing without drugs.

The role of DNA damage response in human embryonic stem cells exposed to atmospheric oxygen tension: Implications for embryo development and differentiation.

Previous retrospective cohort studies have found that, compared with oxygen tension in the uterus and fallopian tubes (2 %-8 %), exposure of pre-implantation embryos to atmospheric oxygen tension (AtmO2, 20 %) during assisted reproductive technology(ART) can affect embryo quality, pregnancy outcomes and offspring health. However, current research on the effects and mechanisms of AtmO2 on the development of embryos and offspring is mainly limited to animal experiments. Human embryonic stem cells (hESCs) play a special and irreplaceable role in the study of early human embryonic development. In this study, we used hESCs as a model to elucidate the possible effects and mechanisms of AtmO2 exposure on human embryonic development. We found that exposure to AtmO2 can reduce cell viability, produce oxidative stress, increase DNA damage, initiate DNA repair, activate autophagy, and increase cell apoptosis. We also noticed that approximately 50 % of hESCs survived, adapted and proliferated through high expression of self-renewal and pluripotency regulatory factors, and affected embryoid body differentiation. These data indicate that hESCs experience oxidative stress, accumulation of DNA damage, and activate DNA damage response under the selective pressure of AtmO2.Some hESCs undergo cell death, whereas other hESCs adapt and proliferate through increased expression of self-renewal genes. The current findings provide in vitro evidence that exposure to AtmO2 during the early preimplantation stage negatively affects hESCs.

Concurrent brain structural and functional alterations in the thalamus of adult survivors of childhood brain tumors: a multimodal MRI study.

Adult survivors of childhood brain tumors often present with cognitive deficits that affect their quality of life. Studying brain structure and function in brain tumor survivors can help understand the underlying mechanisms of their cognitive deficits to improve long-term prognosis of these patients. This study analyzed voxel-based morphometry (VBM) derived from T1-weighted MRI and the amplitude of low-frequency fluctuation (ALFF) from resting-state functional magnetic resonance imaging (rs-fMRI) to examine the structural and functional alterations in 35 brain tumor survivors using 35 matching healthy individuals as controls. Compared with healthy controls, brain tumor survivors had decreased gray matter volumes (GMV) in the thalamus and increased GMV in the superior frontal gyrus. Functionally, brain tumor survivors had lower ALFF values in the inferior temporal gyrus and medial prefrontal area and higher ALFF values in the thalamus. Importantly, we found concurrent but negatively correlated structural and functional alterations in the thalamus based on observed significant differences in GMV and ALFF values. These findings on concurrent brain structural and functional alterations provide new insights towards a better understanding of the cognitive deficits in brain tumor survivors.

SAGL: A self-attention-based graph learning framework for predicting survival of colorectal cancer patients.

BACKGROUND AND OBJECTIVE: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. The accurate survival prediction for CRC patients plays a significant role in the formulation of treatment strategies. Recently, machine learning and deep learning approaches have been increasingly applied in cancer survival prediction. However, most existing methods inadequately represent and leverage the dependencies among features and fail to sufficiently mine and utilize the comorbidity patterns of CRC. To address these issues, we propose a self-attention-based graph learning (SAGL) framework to improve the postoperative cancer-specific survival prediction for CRC patients. METHODS: We present a novel method for constructing dependency graph (DG) to reflect two types of dependencies including comorbidity-comorbidity dependencies and the dependencies between features related to patient characteristics and cancer treatments. This graph is subsequently refined by a disease comorbidity network, which offers a holistic view of comorbidity patterns of CRC. A DG-guided self-attention mechanism is proposed to unearth novel dependencies beyond what DG offers, thus augmenting CRC survival prediction. Finally, each patient will be represented, and these representations will be used for survival prediction. RESULTS: The experimental results show that SAGL outperforms state-of-the-art methods on a real-world dataset, with the receiver operating characteristic curve for 3- and 5-year survival prediction achieving 0.849±0.002 and 0.895±0.005, respectively. In addition, the comparison results with different graph neural network-based variants demonstrate the advantages of our DG-guided self-attention graph learning framework. CONCLUSIONS: Our study reveals that the potential of the DG-guided self-attention in optimizing feature graph learning which can improve the performance of CRC survival prediction.

Molecular characterization of Drosophila melanogaster thymidylate kinase.

Drosophila has been used as an animal model to study pathogenic mechanism of neurological disorders. Thymidylate kinase (TMPK) is an essential enzyme in dTTP synthesis catalyzing the phosphorylation of dTMP to dTDP. Loss of function mutations in the DTYMK gene, coding for TMPK, cause severe microcephaly in human patients. In this study, Drosophila melanogaster TMPK (DmTMPK) was cloned, expressed, purified and characterized. Unlike human TMPK, DmTMPK phosphorylated not only dTMP and dUMP but also dGMP and dIMP although with low efficiency. ATP and dATP are the most efficient phosphate donor but at higher concentration (>1 mM) ATP inhibited DmTMPK activity. Sequence and structural model analysis explain why DmTMPK could phosphorylate purine nucleoside monophosphates. This study has laid a solid foundation for future study of TMPK function in Drosophila.

Single-atom tailored atomically-precise nanoclusters for enhanced electrochemical reduction of CO2-to-CO activity.

The development of facile tailoring approach to adjust the intrinsic activity and stability of atomically-precise metal nanoclusters catalysts is of great interest but remians challenging. Herein, the well-defined Au8 nanoclusters modified by single-atom sites are rationally synthesized via a co-eletropolymerization strategy, in which uniformly dispersed metal nanocluster and single-atom co-entrenched on the poly-carbazole matrix. Systematic characterization and theoretical modeling reveal that functionalizing single-atoms enable altering the electronic structures of Au8 clusters, which amplifies their electrocatalytic reduction of CO2 to CO activity by ~18.07 fold compared to isolated Au8 metal clusters. The rearrangements of the electronic structure not only strengthen the adsorption of the key intermediates *COOH, but also establish a favorable reaction pathway for the CO2 reduction reaction. Moreover, this strategy fixing nanoclusters and single-atoms on cross-linked polymer networks efficiently deduce the performance deactivation caused by agglomeration during the catalytic process. This work contribute to explore the intrinsic activity and stability improvement of metal clusters.

A Gas Therapy Strategy for Intestinal Flora Regulation and Colitis Treatment by Nanogel-Based Multistage NO Delivery Microcapsules.

Current approaches to treating inflammatory bowel disease focus on the suppression of overactive immune responses, the removal of reactive intestinal oxygen species, and regulation of the intestinal flora. However, owing to the complex structure of the gastrointestinal tract and the influence of mucus, current small-molecule and biologic-based drugs for treating colitis cannot effectively act at the site of colon inflammation, and as a result, they tend to exhibit low efficacies and toxic side effects. In this study, nanogel-based multistage NO delivery microcapsules are developed to achieve NO release at the inflammation site by targeting the inflammatory tissues using the nanogel. Surprisingly, oral administration of the microcapsules suppresses the growth of pathogenic bacteria and increases the abundance of probiotic bacteria. Metabolomics further show that an increased abundance of intestinal probiotics promotes the production of metabolites, including short-chain fatty acids and indole derivatives, which modulate the intestinal immunity and restore the intestinal barrier via the interleukin-17 and PI3K-Akt signaling pathways. This work reveals that the developed gas therapy strategy based on multistage NO delivery microcapsules modulates the intestinal microbial balance, thereby reducing inflammation and promoting intestinal barrier repair, ultimately providing a new therapeutic approach for the clinical management of colitis.

Real-world use of first-line pembrolizumab + platinum + taxane combination regimens in recurrent / metastatic head and neck squamous cell carcinoma.

Introduction: The programmed death-1 (PD-1) immune checkpoint inhibitor pembrolizumab is currently approved in the US for the first-line (1L) treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), either alone or in combination with platinum and 5-fluorouracil (5-FU). However, the toxicity of 5-FU has motivated the study of alternate combinations that replace 5-FU with a taxane. The objective of the current study was to describe the baseline characteristics, treatment patterns and sequences, and real-world outcomes of individuals receiving pembrolizumab + platinum + taxane as 1L treatment for R/M HNSCC in the US. Methods: This was a retrospective study of US adults ≥18 years of age receiving pembrolizumab + platinum + taxane as 1L treatment for R/M HNSCC, using electronic health record data from a nationwide de-identified database. Real-world overall survival (rwOS), time on treatment (rwToT), and time to next treatment (rwTTNT) outcomes were assessed using Kaplan-Meier analysis. Results: The study population comprised 83 individuals (80.7% male) with a median age of 64 years. The most common tumor site was the oropharynx (48.2%); 70.0% of these tumors were HPV-positive. A total of 71.1% of the study population had an Eastern Cooperative Oncology Group performance status of 0-1 at index date, 71.8% had a combined positive score for programmed death ligand-1 (PD-L1) expression of ≥1, and 30.8% had a score of ≥20. The median (95% CI) rwOS was 14.9 (8.8-23.3) months, rwToT was 5.3 (4.0-8.2) months, and rwTTNT was 8.7 (6.8-12.3) months. Among the 24 individuals who received a subsequent therapy, the most common second-line therapies were cetuximab-based (n = 9) or pembrolizumab-containing (n = 8) regimens. Conclusions: The rwOS and other real-world outcomes observed for this study population further support pembrolizumab + platinum + taxane combination therapy as a potential 1L treatment option for R/M HNSCC.

CyVerse: Cyberinfrastructure for open science.

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 124,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in three countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.

In situ Mo-doped ZnIn2S4/Ni-Ni Hofmann-type coordination polymer composites for photocatalytic hydrogen evolution reaction.

Solar energy-assisted hydrogen production technology is an essential tool for exploring hydrogen energy. To date, semiconductors have been used as the primary photocatalyst to generate hydrogen via photocatalytic water splitting. However, the high photogenerated electron-hole recombination rate of semiconductor photocatalysts results in a low hydrogen production rate. Herein, the synergistic effect of Mo-ion doping and the incorporation of Ni-based Hofmann-type coordination polymer (Ni-Ni HCP) on the photocatalytic performance of ZnIn2S4 (ZIS) is investigated. The hydrogen production rate of the prepared in-situ Mo doped ZnIn2S4 wrapped Ni-Ni HCP (Ni-Ni HCP/Mo-ZIS) sample under visible-light irradiation is 26.7 mmol g-1h-1, which is 10 times that of pure ZIS. Hydrogen production rate test, microscopic characterization, and density functional theory calculation confirm that the proposed dual modulation approach (combined ion doping and heterogeneous structure construction) could effectively increase the photocatalytic efficiency of ZIS. The stability of prepared samples is also examined by four-cycle photocatalytic hydrogen production tests. The proposed integrated method opens a new route for advancing renewable energy technology towards a sustainable future.

A Retrospective Study of the Patient State Index During General Anesthesia in Infants and Young Children.

This study described electroencephalogram (EEG) parameters in children under general anesthesia, which could monitor patient-specific brain responses to anesthetics and assess the effects of anesthesia. The objective was to detect the patient state index (PSI) and associated factors. We analyzed EEG parameters in patients in the age range 1 to 36 months. Patients were stratified into 2 groups as those aged 1 to 12 months and 13 to 36 months. Sixty-two patients were involved. Spectral edge frequency (SEF), PSI, and blood pressure were lower, and burst suppression rate (BSR) and heart rate were higher in the 1 to 12 months group. The SEF was associated with PSI in both groups. Age and blood pressure were positively associated with PSI, and BSR was negatively related to PSI in children under 1 year of age. Blood pressure was not associated with PSI in the 13 to 36 months age group. We found that the PSI levels did not accurately assess the depth of anesthesia in children under 1 year of age.

Emerging trends and hotspots of the itch research: A bibliometric and visualized analysis.

AIMS: Itch, a common uncomfortable sensory experience, occurs frequently in inflammatory or allergic disorders. In recent years, with the discovery of itch-specific pathways in the peripheral and central nervous system, the association between immunology and neural pathways has gradually emerged as the main mechanism of itch. Although many studies have been conducted on itch, no bibliometric analysis study focusing on this topic has been conducted. This study aimed to explore the research hotspots and trends in the itch field from a bibliometric perspective. METHODS: Publications relevant to itch, published from 2003 to 2022, were retrieved from the Science Citation Index-Expanded of Web of Science Core Collection. Publications were critically reviewed and analyzed with CiteSpace software, Vosviewer, and the bibliometric online analysis platform. Visual maps were conducted in terms of annual production, collaborating countries or institutions, productive authors, core journals, co-cited references, and keyword bursts. RESULTS: 2395 articles on itch that met our criteria were identified and the quantity of publications has been increasing rapidly since 2012. The USA was the most influential country. University Hospital Münster was the institution with the most publications. Gil Yosipovitch was the most prolific author. Atopic dermatitis (AD), intradermal serotonin, chronic pruritus, mechanical itch, gastrin-releasing peptide, substance p, interleukin-31 receptor, histamine-induced itch, bile acid, scratching behavior, and h-4 receptor were the top 11 clusters in co-citation cluster analysis. Keyword burst analysis suggested that treatment, inflammation, and AD are current research hotspots. CONCLUSION: Global publications on itch research have increased steadily and rapidly over the past 20 years. Inflammation and AD are current research hotspots. The neuroimmunological and neuroinflammatory mechanisms of itch, as well as clinical assessment methods and therapeutic targets, will be novel research directions in the future. This study provides guidance for further itch research.

Single-cell transcriptomics reveals variations in monocytes and Tregs between gout flare and remission.

Gout commonly manifests as a painful, self-limiting inflammatory arthritis. Nevertheless, the understanding of the inflammatory and immune responses underlying gout flares and remission remains ambiguous. Here, based on single-cell RNA-Seq and an independent validation cohort, we identified the potential mechanism of gout flare, which likely involves the upregulation of HLA-DQA1+ nonclassical monocytes and is related to antigen processing and presentation. Furthermore, Tregs also play an essential role in the suppressive capacity during gout remission. Cell communication analysis suggested the existence of altered crosstalk between monocytes and other T cell types, such as Tregs. Moreover, we observed the systemic upregulation of inflammatory and cytokine genes, primarily in classical monocytes, during gout flares. All monocyte subtypes showed increased arachidonic acid metabolic activity along with upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2). We also detected a decrease in blood arachidonic acid and an increase in leukotriene B4 levels during gout flares. In summary, our study illustrates the distinctive immune cell responses and systemic inflammation patterns that characterize the transition from gout flares to remission, and it suggests that blood monocyte subtypes and Tregs are potential intervention targets for preventing recurrent gout attacks and progression.

Zebrafish as a model for study of disorders in pyrimidine nucleotide metabolism.

Pyrimidine nucleotides are not only the building blocks of DNA and RNA but also participate in multiple cellular metabolic processes, including protein, lipid and polysaccharide biosynthesis. Pyrimidine nucleotides are synthesized by two distinct pathways-the de novo and salvage pathways. Disorders in pyrimidine nucleotide metabolism cause severe neurodegenerative disorders in human. For example, deficiency in thymidylate kinase, an essential enzyme in dTTP synthesis, causes severe microcephaly in human patients. Zebrafish mutants selected by insertion mutagenesis that results in inactive enzymes in pyrimidine metabolism showed also neurological and developmental disorders. In this work I have summarized current data on neurological and developmental disorders caused by defects in enzymes in pyrimidine nucleotide metabolism in zebrafish and compared to human. All these data suggest that zebrafish is a useful animal model to study pathogenic mechanism of neurological disorders due to defect in pyrimidine nucleotide metabolism.