Schizophrenia-Like Behaviors Arising from Dysregulated Proline Metabolism Are Associated with Altered Neuronal Morphology and Function in Mice with Hippocampal PRODH Deficiency.

Despite decades of research being conducted to understand what physiological deficits in the brain are an underlying basis of psychiatric diseases like schizophrenia, it has remained difficult to establish a direct causal relationship between neuronal dysfunction and specific behavioral phenotypes. Moreover, it remains unclear how metabolic processes, including amino acid metabolism, affect neuronal function and consequently modulate animal behaviors. PRODH, which catalyzes the first step of proline degradation, has been reported as a susceptibility gene for schizophrenia.

The Roles of Histamine Receptor 1 (hrh1) in Neurotransmitter System Regulation, Behavior, and Neurogenesis in Zebrafish.

Histamine receptors mediate important physiological processes and take part in the pathophysiology of different brain disorders. Histamine receptor 1 (HRH1) is involved in the development of neurotransmitter systems, and its role in neurogenesis has been proposed. Altered HRH1 binding and expression have been detected in the brains of patients with schizophrenia, depression, and autism.

Assessment of Stakeholder Perceptions and Cost of Implementing a Telemedicine Specialty Program at Correctional Facilities in North Carolina.

Background Delivering in-person health care to the more than 1.2 million incarcerated adults can be expensive, logistically challenging, fragmented, and pose security risks. The purpose of this study was to evaluate the implementation of a specialty care telemedicine program in statewide prisons in North Carolina during the COVID-19 pandemic.

Global determination of reaction rates and lipid turnover kinetics in Mus musculus.

Metabolism is fundamental to life, but measuring metabolic reaction rates remains challenging. Here, we applied C13 fluxomics to monitor the metabolism of dietary glucose carbon in 12 tissues, 9 brain compartments, and over 1,000 metabolite isotopologues over a 4-day period. The rates of 85 reactions surrounding central carbon metabolism are determined with elementary metabolite unit (EMU) modeling.

Proline Metabolism in Neurological and Psychiatric Disorders.

Proline plays a multifaceted role in protein synthesis, redox balance, cell fate regulation, brain development, and other cellular and physiological processes. Here, we focus our review on proline metabolism in neurons, highlighting the role of dysregulated proline metabolism in neuronal dysfunction and consequently neurological and psychiatric disorders. We will discuss the association between genetic and protein function of enzymes in the proline pathway and the development of neurological and psychiatric disorders.

Changes in Patient Characteristics and Practice Outcomes of a Tele-Urgent Care Clinic Pre- and Post-COVID-19 Telehealth Policy Expansions.

Introduction: The coronavirus 2019 pandemic (COVID-19) has resulted in major changes in lifestyle practices and healthcare delivery. The goal of this study was to examine changes in practice and service outcomes in a telehealth program before and after the federal and private telehealth policy expansion during the COVID-19 pandemic. These findings are particularly useful to understand what may be needed to overcome telehealth challenges in future disasters.

Digital Health Experiences of Incarcerated Populations Using Telemedicine in North Carolina Prisons.

More than 1.2 million adults are incarcerated in the United States and hence, require health care from prison systems. The current delivery of care to incarcerated individualss is expensive, logistically challenging, risk fragmenting care, and pose security risks.

Association between lncRNA-H19 polymorphisms and hepatoblastoma risk in an ethic Chinese population.

H19 polymorphisms are associated with increased susceptibility to several cancers; however, their role in hepatoblastoma remains unclear. In this study, we investigated the association between three H19 polymorphisms (rs2839698 G>A, rs3024270 C>G, rs217727 G>A) and hepatoblastoma susceptibility in 213 hepatoblastoma patients. The rs2839698 and rs3024270 polymorphisms were associated with significantly increased hepatoblastoma risk, with the GG genotype associated with a higher risk of hepatoblastoma than the CC genotype at the rs3024270 locus.

Modeling of Solid-Tumor Microenvironment in Zebrafish (Danio Rerio) Larvae.

The zebrafish larvae have emerged as a powerful model for studying tumorigenesis in vivo, with remarkable conservation with mammals in genetics, molecular and cell biology. Zebrafish tumor models bear the significant advantages of optical clarity in comparison to that in the mammalian models, allowing noninvasive investigation of the tumor cell and its microenvironment at single-cell resolution. Here we review recent progressions in the field of zebrafish models of solid tumor diseases in two main categories: the genetically engineered tumor models in which all cells in the tumor microenvironment are zebrafish cells, and xenograft tumor models in which the tumor microenvironment is composed of zebrafish cells and cells from other species.

Association of CMYC polymorphisms with hepatoblastoma risk.

Background: Single-nucleotide polymorphisms (SNPs) in genes may affect gene expression and contribute to cancer susceptibility. This study aimed to explore the association between gene polymorphisms and hepatoblastoma risk.

Methods: Hepatoblastoma patients and cancer-free controls were recruited and matched by age and sex.

Associations of genetic polymorphisms with Hirschsprung's disease in a Southern Chinese population.

Hirschsprung's disease (HSCR) is a neurodevelopmental disorder characterized by the absence of nerves in intestine with strong genetic components. was found to be associated with HSCR in Korean population waiting for replication in an independent cohort. In the present study, ten single nucleotide polymorphisms (SNPs) in the were selected from Southern Chinese with 1470 HSCR cases and 1473 ethnically matched healthy controls.

rs11655237 C>T Polymorphism Impacts Hepatoblastoma Susceptibility in Chinese Children.

Background: Hepatoblastoma (HB) is the most common hepatic malignancy in children, accounting for approximately 80% of all childhood liver tumors. Previous genome-wide association studies (GWASs) have found that the rs11655237 C>T polymorphism is associated with the risk of several different adult cancers. However, the association between this polymorphism and HB susceptibility remains unclear.

and polymorphisms are not associated with hepatoblastoma susceptibility in Chinese children.

Background: Hepatoblastoma is the most common hepatic malignancy in children, accounting for approximately 80% of all childhood liver tumors. and , members of the gene family, are closely linked to tumorigenesis, and are frequently mutated in a variety of malignancies. They may thus play critical roles in tumorigenesis.

Pleiotropic effect of common variants in Hirschsprung disease and neuroblastoma.

Hirschsprung disease (HSCR) is a heterogeneous congenital disorder that affects the enteric nervous system, while neuroblastoma is an embryonal tumor of the sympathetic nervous system. Familial cases of both HSCR and neuroblastoma appear to be functionally linked to , which plays a key role in the development of neural crest derivatives. However, the association between common variants and disease risk is contested.

Canonical Wnt Signaling Remodels Lipid Metabolism in Zebrafish Hepatocytes following Ras Oncogenic Insult.

There is limited understanding of the effects of major oncogenic pathways and their combinatorial actions on lipid composition and transformation during hepatic tumorigenesis. Here, we report a negative correlation of Wnt/Myc activity with steatosis in human hepatocellular carcinoma (HCC) and perform functional studies using three conditional transgenic zebrafish models. Double-transgenic zebrafish larvae conditionally expressing human and zebrafish or murine together with in hepatocytes led to severe hepatomegaly and significantly attenuated accumulation of lipid droplets and cell senescence triggered by expression alone.

Association of VAMP5 and MCC genetic polymorphisms with increased risk of Hirschsprung disease susceptibility in Southern Chinese children.

Hirschsprung disease (HSCR) is a genetic disorder characterized by the absence of neural crest cells in parts of the intestine. This study aims to investigate the association of vesicle-associated membrane protein 5 () and mutated in colorectal cancer () genetic polymorphisms and their correlated risks with HSCR. We examined the association in four polymorphisms (rs10206961, rs1254900 and rs14242 in , rs11241200 in ) and HSCR susceptibility in a Southern Chinese population composed of 1473 cases and 1469 controls.

Screening in larval zebrafish reveals tissue-specific distribution of fifteen fluorescent compounds.

The zebrafish is a prominent vertebrate model for low-cost whole organism screening. In our recent screening of the distribution patterns of fluorescent compounds in live zebrafish larvae, fifteen compounds with tissue-specific distributions were identified. Several compounds were observed to accumulate in tissues where they were reported to induce side-effects, and compounds with similar structures tended to be enriched in the same tissues, with minor differences.

High Resolution Imaging of DNA Methylation Dynamics using a Zebrafish Reporter.

As one of the major epigenetic modifications, DNA methylation is constantly regulated during embryonic development, cell lineage commitment, and pathological processes. To facilitate real-time observation of DNA methylation, we generated a transgenic zebrafish reporter of DNA methylation (zebraRDM) via knockin of an mCherry-fused methyl-CpG binding domain (MBD) probe driven by the bactin2 promoter. The probe colocalized with heterochromatin, and its intensity was positively correlated with 5 mC immunostaining at a subcellular resolution in early embryos.

[Generation and phenotype analysis of zebrafish mutations of obesity-related genes lepr and mc4r].

Obesity has become a severe public health problem across the world, and seriously affects the health and life quality of human beings. Here we generated lepr and mc4r mutant zebrafish via the CRISPR/Cas9 technique, and performed morphological and functional characterizations of those mutants. We observed that there was no significant phenotypic difference between homozygous mutants and wild-type controls before 2.

Disruption of the gaa Gene in Zebrafish Fails to Generate the Phenotype of Classical Pompe Disease.

The underlying pathogenic lesions of glycogen storage disease type II (GSD II) and the diversity of this disease among different species are still under exploration. Thus, we created an acid alpha-glucosidase (gaa) gene-mutated zebrafish model of GSD II and examined the sequential pathogenic changes. gaa mRNA and protein expression, enzymatic activity, and lysosomal glycogen accumulation were assessed, and the phenotypic changes were compared between wild-type (WT) and gaa-mutated zebrafish.