Geographical patterns and environmental influencing factors of variations in Asterothamnus centraliasiaticus seed traits on Qinghai-Tibetan plateau.

Introduction: Seed traits related to recruitment directly affect plant fitness and persistence. Understanding the key patterns and influencing factors of seed trait variations is conducive to assessing plant colonization and habitat selection. However, the variation patterns of the critical seed traits of shrub species are usually underrepresented and disregarded despite their vital role in alpine desert ecosystems. Methods: This study gathered seeds from 21 Asterothamnus centraliasiaticus populations across the Qinghai-Tibetan Plateau, analyzing geographical patterns of seed traits to identify external environmental influences. Additionally, it explored how seed morphology and nutrients affect germination stress tolerance, elucidating direct and indirect factors shaping seed trait variations. Results: The results present substantial intraspecific variations in the seed traits of A. centraliasiaticus. Seed traits except seed length-to-width ratio (LWR) all vary significantly with geographic gradients. In addition, the direct and indirect effects of climatic variables and soil nutrients on seed traits were verified in this study. Climate mainly influences seed nutrients, and soil nutrients significantly affect seed morphology and seed nutrients. Furthermore, climate directly impacts seed germination drought tolerance index (GDTI) and germination saline-alkali tolerance index (GSTI). Seed germination cold tolerance index (GCTI) is influenced by climate and soil nutrients (mostly SOC). GDTI and GSTI are prominently influenced by seed morphology (largely the seed thousand-grain weight (TGW)), and GCTI is evidently affected by seed nutrients (mainly the content of soluble protein (CSP)). Discussion: The findings of this study amply explain seed trait variation patterns of shrubs in alpine desert ecosystems, possessing significant importance for understanding the mechanism of shrub adaptation to alpine desert ecosystems, predicting the outcomes of environmental change, and informing conservation efforts. This study can be a valuable reference for managing alpine desert ecosystems on the Qinghai-Tibetan Plateau.

Chronic exercise improves renal AT1 and ETB receptor functions via modulating GRK4 expression in obese Zucker rats.

BACKGROUND: Physical activity has profound benefits on health, especially in patients with cardiovascular and metabolic disease. Exercise training can reduce oxidative stress, improve renal function, and thus lower blood pressure. However, the effect of exercise training on angiotensin II type 1 receptors (AT1R) and endothelin subtype B receptors (ETBR)-mediated diuresis and natriuresis in obese Zucker rats is unclear. METHODS: Lean and obese Zucker rats were exercised or placed on a nonmoving treadmill for 8 weeks. Blood pressure was measured by tail-cuff plethysmography, and functions of AT1R and ETBR in the kidney were measured by natriuresis, respectively. RESULTS: Our data showed that exercise training improved glucose and lipid metabolism, renal function and sodium excretion in obese Zucker rats, accompanied by decreased oxidative stress and GRK4 expression in obese Zucker rats. Moreover, exercise training reduced the Candesartan-induced an increase in diuresis and natriuresis and increased ETBR agonists (BQ3020)-mediated diuresis and natriuresis in obese Zucker rats, which were associated with decreased renal AT1R expression and ETBR phosphorylation levels. CONCLUSIONS: The results demonstrate that exercise training lowers blood pressure via improving renal AT1R and ETBR function through modulating GRK4 expression in Obese Zucker Rats and provides potentially effective targets for obesity-related hypertension.

A case of POEMS syndrome comprising of a complicated diagnostic procedure: Case report.

RATIONALE: This article presents the case of a patient with recurrent chronic diarrhea and cachexia who was misdiagnosed, followed by a literature review to summarize the reasons for misdiagnosis of POEMS syndrome and the treatment strategies. PATIENT CONCERNS: The diagnosis and treatment of this patient suggest that with the improvement of M-protein detection levels, the diagnosis of patients with low M-protein levels, such as those with POEMS syndrome, has been greatly aided. DIAGNOSES: POEMS syndrome requires polyneuropathy and monoclonal plasma cell proliferation as mandatory diagnostic criteria. Therefore, patients presenting with polyneuropathy should routinely undergo M-protein testing and consider the possibility of POEMS syndrome. INTERVENTIONS: The patient, in this case, was treated primarily with relatively conservative immunomodulatory agents. OUTCOMES: During follow-up after treatment, the patient's diarrhea and malnutrition showed significant improvement. LESSONS SUBSECTIONS: POEMS syndrome has low clinical specificity and a high rate of misdiagnosis. However, once a definitive diagnosis is made, the treatment outcome is favorable.

Characterization and phylogenetic analysis of the complete chloroplast genome of Asterothamnus centraliasiaticus Novopokr. (Asteraceae: Asterothamnus).

Asterothamnus centraliasiaticus Novopokr., a species of perennial deciduous semi-shrub within the family Asteraceae, has excellent medical, economic, ecological and genetic value. In this study, the chloroplast genome of A. centraliasiaticus was first assembled using Illumina HiSeq2500 sequences. The results indicate that the complete cp genome of A. centraliasiaticus is 152,205 bp in length, and comprises a pair of inverted repeat (IR) regions of 25,031 bp each, a large single-copy (LSC) region of 83,956 bp and a small single-copy (SSC) region of 18,187 bp. The GC content of A. centraliasiaticus is 37.3%. A total of 130 genes were successfully annotated containing 85 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes. The maximum likelihood (ML) phylogenetic analysis based on the complete chloroplast genome data highly supported that A. centraliasiaticus was close to Aster lavandulifolius. These results will provide significant genetic information for the germplasm protection and reasonable development.

METTL3 facilitates renal cell carcinoma progression by PLOD2 m6A-methylation under prolonged hypoxia.

N6-methyladenosine (m6A) is the most prevalent reversible modification in eukaryotic mRNA, and it plays a critical role in tumor progression. The purpose of this study was to investigate the function and regulatory mechanisms of the methyltransferase METTL3 in renal cell carcinoma (RCC). METTL3 expression was upregulated and predicted a poor prognosis in patients with advanced RCC. METTL3 facilitated the proliferation, migration, and invasion of RCC cells, depending on its methylase activity. METTL3 positively regulated the expression of PLOD2, and both genes were triggered under prolonged hypoxia. Mechanistically, hypoxia-induced the binding of HIF-1α to the METTL3 promoter, which enhanced its transcriptional activity. METTL3-mediated m6A modifications of PLOD2 mRNA at 3'UTR region, promoting the translation of PLOD2 protein. Furthermore, silencing METTL3 impaired RCC progression in vitro. In vivo, administration of highly potent and selective METTL3 inhibitor STM2457 showed anti-tumor effects, whereas AAV9-mediated re-transduction of PLOD2 largely abolished the above phenomenon in a subcutaneous mouse model. These findings reveal that hypoxia and HIF-driven METTL3 transcription promote RCC progression by increasing PLOD2 expression in an m6A-dependent manner, suggesting that METTL3 may serve as a novel pharmaceutical intervention for RCC.

The m6A demethylase FTO targets POLQ to promote ccRCC cell proliferation and genome stability maintenance.

BACKGROUND AND AIM: As the first identified m6A demethylase, FTO has been implicated in the progression of various cancers. However, the specific mechanism of FTO in clear cell renal cell carcinoma (ccRCC) remains incompletely understood. In this study, we aimed to explore the potential molecular mechanisms influencing the progression of ccRCC. METHODS: We initially assessed the expression of FTO in tumor and adjacent tissues using TCGA database, RT-qPCR, and Western blot. We then conducted CCK-8, cell cycle analysis, and colony formation assay to investigate the impact of FTO on ccRCC cell proliferation. MeRIP-seq and RNA-seq were employed to identify potential downstream targets of FTO in ccRCC, and these findings were further validated through dual-luciferase reporter assays and MeRIP-qPCR. Then, DNA damage and cell death were assessed separately through gammaH2AX immunofluorescence detection and the LIVE/DEAD Fixable Dead Cell Stain assay, respectively. Subsequently, we identified downstream pathways influenced by FTO's regulation of POLQ through TCGA database analysis and GSEA enrichment analysis. Validation was carried out through Western blot. RESULTS: FTO is highly expressed in ccRCC tissues and cell lines. Furthermore, ROC curve demonstrates that FTO contributes to the diagnosis of ccRCC. FTO modulates m6A modification, consequently influencing the expression of POLQ, thus facilitating cell proliferation and maintaining genome stability in ccRCC. CONCLUSION: FTO could potentially serve as a diagnostic marker for ccRCC. FTO promotes the progression of ccRCC by regulating m6A modification, making the inhibition of FTO a potential novel therapeutic strategy in ccRCC.

Network pharmacology and molecular docking predictions of the active compounds and mechanism of action of Huangkui capsule for the treatment of idiopathic membranous nephropathy.

BACKGROUND: Huangkui Capsule is a single herbal concoction prepared from the flower of Abelmoschus manihot, which is used to treat idiopathic membranous nephropathy (IMN), a frequent pathologically damaging kidney condition. It has been widely utilized to treat a variety of renal disorders, including IMN, in clinical practice. However, the active compounds and mechanism of action underlying the anti-IMN effects of Huangkui Capsule remain unclear. In this study, we aimed to predict the potential active compounds and molecular targets of Huangkui Capsule for the treatment of IMN. METHODS: The possible active components of Huangkui were located using the SymMap v2 database. The targets of these drugs were predicted using Swiss Target Prediction, while IMN-related genes with association scores under 5 were gathered from the GeneCards and DisGeNET databases. The common targets of the disease and the components were determined using VENNY 2.1. Using Cytoscape 3.8.0, a drug-disease network diagram was created. Molecular docking was carried out with Pymol, AutoDock Tools, and AutoDock Vina. RESULTS: With 1260 IMN-related illness genes gathered from GeneCards and DisGeNET databases, we were able to identify 5 potentially active chemicals and their 169 target proteins in Huangkui. Based on degree value, the top 6 targets for Huangkui treatment of IMN were chosen, including AKT, MAPK3, PPARG, MMP9, ESR1, and KDR. CONCLUSION: This work theoretically explains the mechanism of action of Huangkui Capsule in treating IMN and offers a foundation for using Huangkui Capsule in treating IMN in clinical settings. The findings require additional experimental validation.

[1, 25-(OH)2-VitD3 attenuates renal tubulointerstitial fibrosis in diabetic kidney disease by inhibiting Snail1-SMAD3/SMAD4 complex formation].

Objective To investigate the effect of 1, 25-(OH)2-VitD3 (VitD3) on renal tubuleinterstitial fibrosis in diabetic kidney disease. Methods NRK-52E renal tubular epithelial cells were divided into control group (5.5 mmol/L glucose medium treatment), high glucose group (25 mmol/L glucose medium treatment) and high glucose with added VitD3 group (25 mmol/L glucose medium combined with 10-8 mmol/L VitD3). The mRNA and protein expression of Snail1, SMAD3, SMAD4, α-SMA and E-cadherin in NRK-52E cells were detected by real-time quantitative PCR and Western blot analysis respectively. The expression and localization of Snail1, SMAD3 and SMAD4 were detected by immunofluorescence cytochemical staining. The binding of Snail1 with SMAD3/SMAD4 complex to the promoter of Coxsackie-adenovirus receptor (CAR) was detected by chromatin immunoprecipitation. The interaction among Snail1, SMAD3/SMAD4 and E-cadherin were detected by luciferase assay. Small interfering RNA (siRNA) was used to inhibit the expression of Snail1 and SMAD4, and the expression of mRNA of E-cadherin was detected by real-time quantitative PCR. SD rats were randomly divided into control group, DKD group and VitD3-treated group. DKD model was established by injection of streptozotocin (STZ) in DKD group and VitD3-treated group. After DKD modeling, VitD3-treated group was given VitD3 (60 ng/kg) intragastric administration. Control group and DKD group were given normal saline intragastric administration. In the DKD group and VitD3-treated group, insulin (1-2 U/kg) was injected subcutaneously to control blood glucose for 8 weeks. The mRNA and protein levels of Snail1, SMAD3, SMAD4, α-SMA and E-cadherin in renal tissues were detected by real-time quantitative PCR and Western blot analysis respectively. Immunohistochemistry was used to detect the expression and localization of Snail1, SMAD3, SMAD4, α-SMA and E-cadherin in renal tissue. Results Compared with the control group, the mRNA and protein expressions of Snail1, SMAD3, SMAD4 and α-SMA in NRK-52E cells cultured with high glucose and in DKD renal tissues were up-regulated, while E-cadherin expression was down-regulated. After the intervention of VitD3, the expression levels of Snail1, SMAD3, SMAD4, α-SMA and E-cadherin in the DKD model improved to be close to those in the control group. Chromatin immunoprecipitation showed that Snail1 and SMAD3/SMAD4 bound to CAR promoter IV, while VitD3 prevented Snail1 and SMAD3/SMAD4 from binding to CAR promoter IV. Luciferase assay confirmed the interaction among Snail1, SMAD3/SMAD4 and E-cadherin. After the mRNA of Snail1 and SMAD4 was inhibited by siRNA, the expression of E-cadherin induced by high glucose was up-regulated. Conclusion VitD3 could inhibit the formation of Snail1-SMAD3/SMAD4 complex and alleviate the renal tubulointerstitial fibrosis in DKD.

Effect of temperature control conditions on DPF regeneration by nonthermal plasma.

A regeneration test of a diesel particulate filter (DPF) was conducted under different temperature conditions with air as the gas source and a nonthermal plasma (NTP) injection system. We investigated the influence of the ambient temperature on the DPF regeneration performance and the oxidative decomposition amount of particulate matter (PM) and analyzed the changes in the PM oxidation characteristics by thermogravimetric analysis (TGA). The higher the temperature, the lower the decomposition amount of PM was under constant temperature conditions. The decomposition amount of PM was the highest at 80 °C (3.74 g), and the PM at interface P2 was not completely removed. The volume concentrations of the DPF regeneration products (CO and CO2) were higher under variable than constant temperature conditions. In addition, the peak temperature of interface P1 occurred 10-30 min earlier, complete regeneration occurred at interface P2, and DPF regeneration occurred faster than under temperature conditions. The initial temperature of the control device was 110 °C, and the maximum mass of PM oxidation decomposition was 4.26 g after regeneration for 15 min cooling to 80 °C. The main form of elemental carbon (EC) transformed into the low ignition point component and the oxidation activity was improved after NTP injection.

Recent Progress of Transition Metal Phosphides for Photocatalytic Hydrogen Evolution.

Photocatalytic hydrogen evolution can effectively alleviate the troublesome global energy crisis by converting solar energy into the chemical energy of hydrogen. In order to realize efficient hydrogen generation, a variety of semiconductor materials have been extensively investigated, including TiO2 , CdS, g-C3 N4 , metal-organic frameworks (MOFs), and others. In recent years, to achieve higher photocatalytic performance and reach the level of large-scale industrial applications, photocatalysts decorated with transition metal phosphides (TMPs) have shone brightly because of their low cost, stable physical and chemical properties, and substitution for precious metals of TMPs. This Review highlights the preparation methods and properties associated with photocatalysis of TMPs. Moreover, the H2 generation efficiency of photocatalysts loaded with TMPs and the roles of TMPs in catalytic systems are also studied systematically. Apart from being co-catalysts, several TMPs can also serve as host catalysts to boost the activity of photocatalytic composites. Finally, the development prospects and challenges of TMPs are put forward, which is valuable for future researchers to expand the application of TMPs in photocatalytic directions and to develop more active photocatalytic systems.

Paeoniflorin: a monoterpene glycoside from plants of Paeoniaceae family with diverse anticancer activities.

OBJECTIVES: Paeoniflorin, a representative pinane monoterpene glycoside in plants of Paeoniaceae family, possesses promising anticancer activities on diverse tumours. This paper summarized the advance of Paeoniflorin on cancers in vivo and in vitro, discussed the related molecular mechanisms, as well as suggested some perspectives of the future investigations. KEY FINDINGS: Anticancer activities of paeoniflorin have been comprehensively investigated, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer, glioma, bladder cancer and leukaemia. Furthermore, the potential molecular mechanisms corresponding to the antitumour effects of Paeoniflorin might be related to the following aspects: inhibition of tumour cell proliferation and neovascularization, induction apoptosis, and inhibition of tumour invasion and metastasis. SUMMARY: Paeoniflorin has wide spectrum antitumour activities; however, in vivo and clinical investigations on antitumour effect of Paeoniflorin are lacking which should be focused on further studies. Our present review on antitumour effects of Paeoniflorin would be beneficial for the further molecular mechanisms study, candidate antitumour drug development and clinical research of Paeoniflorin in the future.

[Down-regulation of p38 MAPK and collagen by 1, 25-(OH)2-VD3 in rat models of diabetic nephropathy].

Objective To investigate the effect of 1, 25-(OH)2-VD3 on collagen type III (Col3), collagen type IV (Col4) and p38 mitogen-activated protein kinase (p38 MAPK) in rat models of type 2 diabetic nephropathy, and explore the relationships of p38MAPK with Col3 and Col4. Methods Rat models of type 2 diabetic nephropathy were induced by streptozocin (STZ, 30 mg/kg) combined with high-glucose-and-fat diet. Sixty rats were randomly divided into control group, model group, 1, 25-(OH)2-VD3 treatment group [given 1, 25-(OH)2-VD3 6 ng/(100 g.d) after modeling] and insulin group (given 2-3 U insulin after modeling). After 8 weeks' intervention, serum creatinine (Scr), blood urea nitrogen (BUN) and 24-hour proteinuria were detected in all groups. Periodic acid-Schiff (PAS) staining was used to observe the kidney pathological changes, and immunohistochemical staining and Western blotting were performed to determine p38 MAPK Col3 and Col4 expressions in rat renal interstitium. Spearman method was applied to the correlation analysis. Results Compared with the model group, blood glucose, Scr, BUN, 24-hour proteinuria and impaired renal interstitial area were all reduced in the 1, 25-(OH)2-VD3 treatment group and the insulin group. Compared with the control group, the expressions of Col3, Col4 and p38 MAPK were higher in the model group, and lower in the 1, 25-(OH)2-VD3 treatment group and the insulin group. Correlation analysis showed that 24-hour proteinuria was positively related with p38 MAPK, Col3, Col4 and immunohistochemical results; p38MAPK was positively correlated with Col3 and Col4 expressions. Conclusion Col3, Col4 and p38MAPK are up-regulated in rat models of type 2 diabetic nephropathy. The 1, 25-(OH)2-VD3 might attenuates the progression of renal interstitial fibrosis via down-regulating p38 MAPK, Col3 and Col4.

Joint mouse-human phenome-wide association to test gene function and disease risk.

Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for ∼5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of ∼4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets--by far the largest coherent phenome for any experimental cohort (www.genenetwork.org). We tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human.

[Effects of Yishen Shengjing Capsules on semen quality and gonadal hormone levels in rats with dibutyl phthalate-induced reproductive function injury].

OBJECTIVE: To study the possible pathogenesis of infertility caused by dibutyl phthalate (DBP) and investigate the effects of Yishen Shengjing Capsules (YSC, kidney-tonifying and essence-producing capsules) on DBP-induced reproductive function injury and its possible action mechanisms in male Wistar rats. METHODS: Models of DBP-induced reproductive function injury were made in 80 male Wistar rats and another 20 were used as blank controls. After modeling, the model rats were randomly divided into a model control, a high-dose YSC, a medium-dose YSC, and a low-dose YSC group. Four weeks after intervention, all the animals were sacrified for observation of the histomorphologic changes in the testis under the light microscope, measurement of sperm concentration, motility and abnormality, and determination of the levels of serum testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by radioimmunoassay. RESULTS: Compared with the blank controls, the model rats showed obvious pathological changes in testicular histomorphology, significantly decreased sperm concentration and motility, increased sperm abnormality, reduced contents of serum T and LH, and elevated the level of serum FSH (P<0.01). After 4 weeks of medication, the animals of the high-, medium-, and low-dose YSC groups, in comparison with the model controls, exhibited different degrees of recovery from testicular histomorphological damage, remarkably increased sperm concentration and motility, decreased sperm abnormality, elevated levels of serum T and LH, and reduced content of serum FSH (P<0.01). There were statistically significant differences in all the parameters above between the high-dose YSC and medium- and low-dose YSC groups (P<0.01). CONCLUSIONS: DBP reduces sperm motility and concentration, increases sperm abnormality, causes damage to the morphological structure of the rat testis, decreases the contents of serum T and LH, and elevates the level of the serum FSH. Yishen Shengjing Capsules can improve DBP-induced productive function injury, increase sperm motility and concentration, decrease sperm abnormality, elevate the level of serum T and LH, reduce the content of serum FSH, improve the morphological structure of the testis, and thus promote the reproductive function of the male rat.

rFN/Cad-11-modified collagen type II biomimetic interface promotes the adhesion and chondrogenic differentiation of mesenchymal stem cells.

Properties of the cell-material interface are determining factors in the successful function of cells for cartilage tissue engineering. Currently, cell adhesion is commonly promoted through the use of polypeptides; however, due to their lack of complementary or modulatory domains, polypeptides must be modified to improve their ability to promote adhesion. In this study, we utilized the principle of matrix-based biomimetic modification and a recombinant protein, which spans fragments 7-10 of fibronectin module III (heterophilic motif) and extracellular domains 1-2 of cadherin-11 (rFN/Cad-11) (homophilic motif), to modify the interface of collagen type II (Col II) sponges. We showed that the designed material was able to stimulate cell proliferation and promote better chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) in vitro than both the FN modified surfaces and the negative control. Further, the Col II/rFN/Cad-11-MSCs composite stimulated cartilage formation in vivo; the chondrogenic effect of Col II alone was much less significant. These results suggested that the rFN/Cad-11-modified collagen type II biomimetic interface has dual biological functions of promoting adhesion and stimulating chondrogenic differentiation. This substance, thus, may serve as an ideal scaffold material for cartilage tissue engineering, enhancing repair of injured cartilage in vivo.

A transposon in Comt generates mRNA variants and causes widespread expression and behavioral differences among mice.

BACKGROUND: Catechol-O-methyltransferase (COMT) is a key enzyme responsible for the degradation of dopamine and norepinephrine. COMT activity influences cognitive and emotional states in humans and aggression and drug responses in mice. This study identifies the key sequence variant that leads to differences in Comt mRNA and protein levels among mice, and that modulates synaptic function and pharmacological and behavioral traits. METHODOLOGY/PRINCIPAL FINDINGS: We examined Comt expression in multiple tissues in over 100 diverse strains and several genetic crosses. Differences in expression map back to Comt and are generated by a 230 nt insertion of a B2 short interspersed element (B2 SINE) in the proximal 3' UTR of Comt in C57BL/6J. This transposon introduces a premature polyadenylation signal and creates a short 3' UTR isoform. The B2 SINE is shared by a subset of strains, including C57BL/6J, A/J, BALB/cByJ, and AKR/J, but is absent in others, including DBA/2J, FVB/NJ, SJL/J, and wild subspecies. The short isoform is associated with increased protein expression in prefrontal cortex and hippocampus relative to the longer ancestral isoform. The Comt variant causes downstream differences in the expression of genes involved in synaptic function, and also modulates phenotypes such as dopamine D1 and D2 receptor binding and pharmacological responses to haloperidol. CONCLUSIONS/SIGNIFICANCE: We have precisely defined the B2 SINE as the source of variation in Comt and demonstrated that a transposon in a 3' UTR can alter mRNA isoform use and modulate behavior. The recent fixation of the variant in a subset of strains may have contributed to the rapid divergence of inbred strains.

Characterization of kynurenine aminotransferase III, a novel member of a phylogenetically conserved KAT family.

Kynurenine aminotransferase (KAT) is an enzyme responsible for synthesis of kynurenic acid (KYNA), a well established neuroprotective and anticonvulsant agent, involved in synaptic transmission and implicated in the pathophysiology of schizophrenia, Huntington's disease and other neurological disorders. We have shown previously that kat2-/- mice had lower hippocampal KYNA levels and were more hyperactive than wild-type mice. However, these abnormalities occur early and are transitory coinciding with restoration of KYNA levels, suggesting that compensatory changes or ontogenetic expression of another unknown homolog may account for the normalization of KYNA levels in the adult kat2-/- mice brain. Here, we report the isolation of a novel KAT molecule, kat3, from mouse and human brain cDNA libraries. The encoded 454 amino acids of human KAT III share 64.8% similarity to that of KAT I and 30.1% to KAT II. Northern blot analysis demonstrated that kat3 mRNA is widely expressed but with higher expression levels in liver, kidney, heart, and neuroendocrine tissues. RT-PCR and Northern analysis showed that kat3 expression starts as early as postnatal day (PND) 7 and peaks in adult. The mRNA level of kat3 and kat1 when measured together is significantly higher at PND 60 in kat2-/- mice than those of wild-type mice indicating possible co-regulation of expression levels. RNA-interference (RNAi) directed towards transcripts for either R03A10.4 or F28H6.3 in Caenorhabditis elegans which are kat1 and kat3 orthologs, respectively, did not result in any gross abnormalities. Our results show that upregulation of kat3 and kat1 may be responsible for the phenotypic rescue on kat2-/- mice.