Jasmonate regulates plant resistance to Pectobacterium brasiliense by inducing indole glucosinolate biosynthesis.

Pectobacterium brasiliense (P. brasiliense) is a necrotrophic bacterium that causes the soft rot disease in Brassica rapa. However, the mechanisms underlying plant immune responses against necrotrophic bacterial pathogens with a broad host range are still not well understood. Using a flg22-triggered seedling growth inhibition (SGI) assay with 455 Brassica rapa inbred lines, we selected six B. rapa flagellin-insensitive lines (Brfin2-7) and three B. rapa flagellin-sensitive lines (Brfs1-3). Brfin lines showed compromised flg22-induced immune responses (oxidative burst, mitogen-activated protein kinase (MAPK) activation, and seedling growth inhibition) compared to the control line R-o-18; nevertheless, they were resistant to P. brasiliense. To explain this, we analyzed the phytohormone content and found that most Brfin lines had higher P. brasiliense-induced jasmonic acid (JA) than Brfs lines. Moreover, MeJA pretreatment enhanced the resistance of B. rapa to P. brasiliense. To explain the correlation between the resistance of Brfin lines to P. brasiliense and activated JA signaling, we analyzed pathogen-induced glucosinolate (GS) content in B. rapa. Notably, in Brfin7, the neoglucobrassicin (NGBS) content among indole glucosinolates (IGS) was significantly higher than that in Brfs2 following P. brasiliense inoculation, and genes involved in IGSs biosynthesis were also highly expressed. Furthermore, almost all Brfin lines with high JA levels and resistance to P. brasiliense had higher P. brasiliense-induced NGBS levels than Brfs lines. Thus, our results show that activated JA-mediated signaling attenuates flg22-triggered immunity but enhances resistance to P. brasiliense by inducing indole glucosinolate biosynthesis in Brassica rapa. This study provides novel insights into the role of JA-mediated defense against necrotrophic bacterial pathogens within a broad host range.

The neuroprotective effects of Lutongkeli in traumatic brain injury rats by anti-apoptosis mechanism.

PURPOSE: To explore the neuroprotective effects of Lutongkeli (LTKL) in traumatic brain injury (TBI) and detect the related mechanism. METHODS: TBI model was established with LTKL administration (2 and 4 g/kg/d, p.o.). Motor function of rats was examined by Rotarod test. Nissl staining was used to show neuron morphology. Furthermore, the disease-medicine common targets were obtained with the network pharmacology and analyzed with Kyoto Encyclopedia of Genes and Genomes. Lastly, the predicted targets were validated by real-time polymerase chain reaction. RESULTS: After LTKL administration, neural behavior was significantly improved, and the number of spared neurons in brain was largely increased. Moreover, 68 bioactive compounds were identified, corresponding to 148 LTKL targets; 2,855 genes were closely associated with TBI, of which 87 overlapped with the LTKL targets and were considered to be therapeutically relevant. Functional enrichment analysis suggested LTKL exerted its pharmacological effects in TBI by modulating multiple pathways including apoptosis, inflammation, etc. Lastly, we found LTKL administration could increase the mRNA level of Bcl-2 and decrease the expression of Bax and caspase-3. CONCLUSIONS: This study reported the neuroprotective effect of LTKL against TBI is accompanied with anti-apoptosis mechanism, which provides a scientific explanation for the clinical application of LTKL in the treatment of TBI.

Tumorigenic and immunological roles of Heat shock protein A2 in pancreatic cancer: a bioinformatics analysis.

OBJECTIVE: Heat shock protein A2 has been reported to be tightly associated with tumorigenesis and tumor progression. This study aimed to determine the oncogenic and immunological roles of Heat shock protein A2 in pancreatic cancer by bioinformatics. METHODS: Expression of Heat shock protein A2 in tumorous and normal specimens of pancreatic cancer was analyzed using the Cancer Genome Atlas and the Cancer Genome Atlas + Genotype-Tissue Expression data sets, respectively. Relationships of Heat shock protein A2 expression with immune infiltrates in pancreatic cancer were assessed. Heat shock protein A2-associated coexpressed genes in pancreatic cancer were obtained, followed by the implementation of enrichment analysis. RESULTS: The data demonstrated that Heat shock protein A2 was significantly overexpressed in tumorous samples compared with normal samples. Heat shock protein A2 expression was remarkably positively interrelated with CD8+ T cell, neutrophil, dendritic cell, and macrophage, but not with CD4+ T and B cells. Heat shock protein A2 expression was markedly positively relevant to both cancer-associated fibroblast and endothelial cell. Enrichment data revealed that Heat shock protein A2 was intimately involved in the tumorigenesis and progression of pancreatic cancer. CONCLUSION: Heat shock protein A2 is upregulated in pancreatic cancer and is closely associated with tumor immunity and aggressive progression.

Tumorigenic and immunological roles of Heat shock protein A2 in pancreatic cancer: a bioinformatics analysis

SUMMARY OBJECTIVE: Heat shock protein A2 has been reported to be tightly associated with tumorigenesis and tumor progression. This study aimed to determine the oncogenic and immunological roles of Heat shock protein A2 in pancreatic cancer by bioinformatics. METHODS: Expression of Heat shock protein A2 in tumorous and normal specimens of pancreatic cancer was analyzed using the Cancer Genome Atlas and the Cancer Genome Atlas + Genotype-Tissue Expression data sets, respectively. Relationships of Heat shock protein A2 expression with immune infiltrates in pancreatic cancer were assessed. Heat shock protein A2-associated coexpressed genes in pancreatic cancer were obtained, followed by the implementation of enrichment analysis. RESULTS: The data demonstrated that Heat shock protein A2 was significantly overexpressed in tumorous samples compared with normal samples. Heat shock protein A2 expression was remarkably positively interrelated with CD8+ T cell, neutrophil, dendritic cell, and macrophage, but not with CD4+ T and B cells. Heat shock protein A2 expression was markedly positively relevant to both cancer-associated fibroblast and endothelial cell. Enrichment data revealed that Heat shock protein A2 was intimately involved in the tumorigenesis and progression of pancreatic cancer. CONCLUSION: Heat shock protein A2 is upregulated in pancreatic cancer and is closely associated with tumor immunity and aggressive progression.

Effects of lifestyle interventions on glucose regulation and diabetes risk in adults with impaired glucose tolerance or prediabetes: a meta-analysis

ABSTRACT The prevalence of diabetes mellitus is increasing and is related to sedentary lifestyles and obesity. Many studies were published on the effect of lifestyle interventions on glucose regulation and delay the onset of diabetes in adults with impaired glucose tolerance (IGT) or prediabetes. This study aimed to investigate the role of lifestyle interventions in individuals with IGT or prediabetes using a meta-analytic approach. PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched from their inception up to January 2020 to select eligible randomized controlled trials (RCTs). The weighted mean difference (WMD; for fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPPG)) or relative risk (RR; for the risk of diabetes) with 95% confidence interval (CI) were calculated for pooled effect estimates using the random-effects model. Thirteen RCTs involving 3376 individuals with IGT or prediabetes were selected for this meta-analysis. The results showed that lifestyle interventions were associated with lower FPG (WMD: -0.14; 95% CI: -0.24 to -0.05 mmol/L; p=0.004) and 2hPPG (WMD: -0.66; 95% CI: -1.12 to -0.20 mmol/L; p=0.005) in adults with IGT or prediabetes. Moreover, the risk of diabetes was significantly reduced in individuals who received lifestyle interventions (RR: 0.75; 95% CI: 0.60-0.95; p=0.015). Lifestyle interventions could help improve glucose dysregulation and prevent the progression of diabetes in adults with IGT or prediabetes. Further large-scale RCTs should be conducted to assess the effects of long-term lifestyle interventions on diabetic complications in adults with IGT or prediabetes.

Effects of lifestyle interventions on glucose regulation and diabetes risk in adults with impaired glucose tolerance or prediabetes: a meta-analysis.

The prevalence of diabetes mellitus is increasing and is related to sedentary lifestyles and obesity. Many studies were published on the effect of lifestyle interventions on glucose regulation and delay the onset of diabetes in adults with impaired glucose tolerance (IGT) or prediabetes. This study aimed to investigate the role of lifestyle interventions in individuals with IGT or prediabetes using a meta-analytic approach. PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched from their inception up to January 2020 to select eligible randomized controlled trials (RCTs). The weighted mean difference (WMD; for fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPPG)) or relative risk (RR; for the risk of diabetes) with 95% confidence interval (CI) were calculated for pooled effect estimates using the random-effects model. Thirteen RCTs involving 3376 individuals with IGT or prediabetes were selected for this meta-analysis. The results showed that lifestyle interventions were associated with lower FPG (WMD: -0.14; 95% CI: -0.24 to -0.05 mmol/L; p=0.004) and 2hPPG (WMD: -0.66; 95% CI: -1.12 to -0.20 mmol/L; p=0.005) in adults with IGT or prediabetes. Moreover, the risk of diabetes was significantly reduced in individuals who received lifestyle interventions (RR: 0.75; 95% CI: 0.60-0.95; p=0.015). Lifestyle interventions could help improve glucose dysregulation and prevent the progression of diabetes in adults with IGT or prediabetes. Further large-scale RCTs should be conducted to assess the effects of long-term lifestyle interventions on diabetic complications in adults with IGT or prediabetes.

The neuroprotective effects of Lutongkeli in traumatic brain injury rats by anti-apoptosis mechanism

Purpose: To explore the neuroprotective effects of Lutongkeli (LTKL) in traumatic brain injury (TBI) and detect the related mechanism. Methods: TBI model was established with LTKL administration (2 and 4 g/kg/d, p.o.). Motor function of rats was examined by Rotarod test. Nissl staining was used to show neuron morphology. Furthermore, the disease-medicine common targets were obtained with the network pharmacology and analyzed with Kyoto Encyclopedia of Genes and Genomes. Lastly, the predicted targets were validated by real-time polymerase chain reaction. Results: After LTKL administration, neural behavior was significantly improved, and the number of spared neurons in brain was largely increased. Moreover, 68 bioactive compounds were identified, corresponding to 148 LTKL targets; 2,855 genes were closely associated with TBI, of which 87 overlapped with the LTKL targets and were considered to be therapeutically relevant. Functional enrichment analysis suggested LTKL exerted its pharmacological effects in TBI by modulating multiple pathways including apoptosis, inflammation, etc. Lastly, we found LTKL administration could increase the mRNA level of Bcl-2 and decrease the expression of Bax and caspase-3. Conclusions: This study reported the neuroprotective effect of LTKL against TBI is accompanied with anti-apoptosis mechanism, which provides a scientific explanation for the clinical application of LTKL in the treatment of TBI.

Gout of feet and ankles in different disease durations: diagnostic value of single-source DECT and evaluation of urate deposition with a novel semi-quantitative DECT scoring system

Abstract Objectives: To investigate the diagnostic performance of single-source dual-energy computed tomography (DECT) based on gemstone spectral imaging technology (including Discovery CT750HD and Revolution CT) in patients with suspected feet/ankles gouty arthritis, and evaluate the urate deposition with a novel semi-quantitative DECT scoring system. Methods: A total of 196 patients were consecutively included. Feet and ankles were evaluated in all patients by single-source DECT scan. The 2015 EULAR/ACR criteria were used as the reference for the diagnosis of gout. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of DECT for the diagnosis of gout in the early (≤1 year), middle (1-3 years), and late (> 3 years) disease durations were calculated. Besides, a novel semi-quantitative DECT scoring system was assessed for the measurement of urate deposition, and the correlation between the scores and the clinical and serological data were also evaluated. Moreover, the influences of artifacts on the diagnostic performance of DECT were also determined. Results: The sensitivity, specificity, and AUC of DECT in 196 patients were 38.10, 96.43%, and 0.673 in the early-stage group; 62.96, 100.00%, and 0.815 in the middle-stage group; and 77.55, 87.50%, and 0.825 in the late-stage group, respectively. The overall diagnostic accuracies in the AUC of DECT (Discovery CT750HD and Revolution CT) in the middle and late stages of gout were higher than that in the early stage of gout. Besides, the monosodium urate crystals were deposited on the first metatarsophalangeal joints and ankles/midfeet. Age, the presence of tophus, bone erosion, and disease duration considerably affected the total urate score. No statistical difference in the positive detection of nail artifact, skin artifact, vascular calcification, and noise artifact was found between the case and control groups. Conclusion: DECT (Discovery CT750HD and Revolution CT) showed promising diagnostic accuracy for the detection of urate crystal deposition in gout but had limited diagnostic sensitivity for short-stage gout. Longer disease duration, the presence of tophus, and bone erosion were associated with the urate crystal score system. The artifacts do not remarkably affect the diagnostic performance of DECT in gout.

Upregulation of miR-129-5p increases the sensitivity to Taxol through inhibiting HMGB1-mediated cell autophagy in breast cancer MCF-7 cells.

Although Taxol has improved the survival of cancer patients as a first-line chemotherapeutic agent, an increasing number of patients develop resistance to Taxol after prolonged treatment. The potential mechanisms of cancer cell resistance to Taxol are not completely clear. It has been reported that microRNAs (miRNAs) are involved in regulating the sensitivity of cancer cells to various chemotherapeutic agents. In this study, we aimed to explore the role of miR-129-5p in regulating the sensitivity of breast cancer cells to Taxol. Cell apoptosis and autophagy, and the sensitivity of MCF-7 cells to Taxol were assessed with a series of in vitro assays. Our results showed that the inhibition of autophagy increased the Taxol-induced apoptosis and the sensitivity of MCF-7 cells to Taxol. Up-regulation of miR-129-5p also inhibited autophagy and induced apoptosis. Furthermore, miR-129-5p overexpression increased the sensitivity of MCF-7 cells to Taxol. High mobility group box 1 (HMGB1), a target gene of miR-129-5p and a regulator of autophagy, was negatively regulated by miR-129-5p. We found that interference of HMGB1 enhanced the chemosensitivity of Taxol by inhibiting autophagy and inducing apoptosis in MCF-7 cells. Taken together, our findings suggested that miR-129-5p increased the chemosensitivity of MCF-7 cells to Taxol through suppressing autophagy and enhancing apoptosis by inhibiting HMGB1. Using miR-129-5p/HMGB1/autophagy-based therapeutic strategies may be a potential treatment for overcoming Taxol resistance in breast cancer.

Upregulation of miR-129-5p increases the sensitivity to Taxol through inhibiting HMGB1-mediated cell autophagy in breast cancer MCF-7 cells

Although Taxol has improved the survival of cancer patients as a first-line chemotherapeutic agent, an increasing number of patients develop resistance to Taxol after prolonged treatment. The potential mechanisms of cancer cell resistance to Taxol are not completely clear. It has been reported that microRNAs (miRNAs) are involved in regulating the sensitivity of cancer cells to various chemotherapeutic agents. In this study, we aimed to explore the role of miR-129-5p in regulating the sensitivity of breast cancer cells to Taxol. Cell apoptosis and autophagy, and the sensitivity of MCF-7 cells to Taxol were assessed with a series of in vitro assays. Our results showed that the inhibition of autophagy increased the Taxol-induced apoptosis and the sensitivity of MCF-7 cells to Taxol. Up-regulation of miR-129-5p also inhibited autophagy and induced apoptosis. Furthermore, miR-129-5p overexpression increased the sensitivity of MCF-7 cells to Taxol. High mobility group box 1 (HMGB1), a target gene of miR-129-5p and a regulator of autophagy, was negatively regulated by miR-129-5p. We found that interference of HMGB1 enhanced the chemosensitivity of Taxol by inhibiting autophagy and inducing apoptosis in MCF-7 cells. Taken together, our findings suggested that miR-129-5p increased the chemosensitivity of MCF-7 cells to Taxol through suppressing autophagy and enhancing apoptosis by inhibiting HMGB1. Using miR-129-5p/HMGB1/autophagy-based therapeutic strategies may be a potential treatment for overcoming Taxol resistance in breast cancer.

Morphological observation of bone marrow mesenchymal stem cells under matrigel three dimensional culture conditions / Observación morfológica de células madre mesenquimales de médula ósea en condiciones de cultivo tridimensional con matrigel

SUMMARY: Matrigel is a basement membrane matrix extracted from the EHS mouse tumor containing extracellular matrix protein, its main components are laminin, type IV collagen, nestin, heparin sulfate, growth factor and matrix metalloproteinase.At room temperature, Matrigel polymerized to form a three dimensional matrix with biological activity. It can simulate the structure, composition, physical properties and functions of the cell basement membrane in vivo, which is beneficial to the culture and differentiation of the cells in vitro, and can be used for the study of cell morphology, biochemical function, migration, infection and gene expression. In this study, Matrigel three-dimensional culture model of bone marrow mesenchymal stem cells(BMSCs) was established, and its morphology, proliferation and survival were observed. BMSCs were isolated and cultured with whole bone marrow adherence method. The Second generation BMSCs with good growth condition were selected and mixed with Matrigel to form cell gel complexes. The morphology and proliferation of mesenchymal stem cells were observed by phase contrast microscope and HE staining,Live/Dead staining was used to evaluate the cell activity.Phase contrast microscopy showed that BMSCs were reticulated in Matrigel and proliferated well, After 7 days, the matrix gel gradually became soft and collapsed, a few cell reticular crosslinking growth was seen at 14 days; HE staining showed that the cytoplasm of the cells was larger on the fourth day and the cells were elongated and cross-linked on the seventh day; Live/dead staining showed that most cells showed green fluorescence with the prolongation of culture time, on the first, 4 and 7 days, the activity of bone marrow mesenchymal stem cells in Matrigel gradually increased, and the percentages were 92.57 %, 95.54 % and 97.37 %, respectively. Matrigel three-dimensional culture system can maintain the morphology, function and proliferation ability of bone marrow mesenchymal stem cells.

RESUMEN: Matrigel es una matriz de membrana basal extraída del tumor de ratón EHS que contiene proteína de matriz extracelular. Los componentes principales son laminina, el colágeno tipo IV, nestina, sulfato de heparina, factor de crecimiento y metaloproteinasa de matriz. A temperatura ambiente, Matrigel se polimerizó para formar una matriz tridimensional. Es posible simular la estructura, la composición, las propiedades físicas y las funciones de la membrana basal celular in vivo, lo que es beneficioso para el cultivo y la diferenciación de las células in vitro, y se puede utilizar para el estudio de la morfología celular, la función bioquímica, la migración, infección y expresión génica. En este estudio, se estableció el modelo de cultivo tridimensional Matrigel de células madre mesenquimales de médula ósea (BMSC), y se observó su morfología, proliferación y supervivencia. Las BMSC fueron aisladas y cultivadas con el método de adherencia de la médula ósea completa. Se seleccionaron las BMSC de segunda generación con buenas condiciones de crecimiento y se mezclaron con Matrigel para formar complejos de gel de células. La morfología y la proliferación de las células madre mesenquimales se observaron con microscopio de contraste de fase y se tiñó con Hematoxilina-Eosina (HE); para evaluar la actividad celular se usó la tinción Live/Dead. La microscopía de contraste mostró que las BMSC se reticularon en Matrigel y proliferaron bien. Después de 7 días, se observó que el gel de matriz gradualmente se volvió blando y colapsó, y se visualizó un cruce transversal de algunas células reticulares a los 14 días. La tinción mostró que la mayoría de las células mostraron una fluorescencia verde con la prolongación del tiempo de cultivo; en los primeros 4 y 7 días, la actividad de las células madre mesenquimales de la médula ósea en Matrigel aumentó gradualmente y los porcentajes fueron de 92,57 %, 95,54 % y 97,37 %, respectivamente. El sistema de cultivo tridimensional de Matrigel puede mantener la morfología, la función y la capacidad de proliferación de las células madre mesenquimales de la médula ósea.

The emergence of the hyperinvasive vine, Mikania micrantha (Asteraceae), via admixture and founder events inferred from population transcriptomics.

Biological invasions that involve well-documented rapid adaptations to new environments provide unequalled opportunities for testing evolutionary hypotheses. Mikania micrantha Kunth (Asteraceae), a perennial herbaceous vine native to tropical Central and South America, successfully invaded tropical Asia in the early 20th century. It is regarded as one of the most aggressive weeds in the world. To elucidate the molecular and evolutionary processes underlying this invasion, we extensively sampled this weed throughout its invaded range in South-East and South Asia and surveyed its genetic structure using variants detected from population transcriptomics. Clustering results suggest that more than one source population contributed to this invasion. Computer simulations using genomewide genetic variation support a scenario of admixture and founder events during invasion. The genes differentially expressed between native and invasive populations were found to be involved in oxidative and high light intensity stress responses, pointing to a possible ecological mechanism of adaptation. Our results provide a foundation for further detailed mechanistic and population studies of this ecologically and economically important invasion. This line of research promises to provide new mitigation strategies for invasive species as well as insights into mechanisms of adaptation.

Determining the phylogenetic and phylogeographic origin of highly pathogenic avian influenza (H7N3) in Mexico.

Highly pathogenic (HP) avian influenza virus (AIV) H7N3 outbreaks occurred 3 times in the Americas in the past 10 years and caused severe economic loss in the affected regions. In June/July 2012, new HP H7N3 outbreaks occurred at commercial farms in Jalisco, Mexico. Outbreaks continued to be identified in neighbouring states in Mexico till August 2013. To explore the origin of this outbreak, time resolved phylogenetic trees were generated from the eight segments of full-length AIV sequences in North America using BEAST. Location, subtype, avian host species and pathogenicity were modelled as discrete traits upon the trees using continuous time Markov chains. A further joint analysis among segments was performed using a hierarchical phylogenetic model (HPM) which allowed trait rates (location, subtype, host species) to be jointly inferred across different segments. The complete spatial diffusion process was visualised through virtual globe software. Our result indicated the Mexico HP H7N3 originated from the large North America low pathogenicity AIV pool through complicated reassortment events. Different segments were contributed by wild waterfowl from different N. American flyways. Five of the eight segments (HA, NA, NP, M, NS) were introduced from wild birds migrating along the central North American flyway, and PB2, PB1 and PA were introduced via the western North American flyway. These results highlight a potential role for Mexico as a hotspot of virus reassortment as it is where wild birds from different migration routes mix during the winter.

Differential gene expression between wild-type and Gulo-deficient mice supplied with vitamin C.

The aim of this study was to test the hypothesis that hepatic vitamin C (VC) levels in VC deficient mice rescued with high doses of VC supplements still do not reach the optimal levels present in wild-type mice. For this, we used a mouse scurvy model (sfx) in which the L-gulonolactone oxidase gene (Gulo) is deleted. Six age- (6 weeks old) and gender- (female) matched wild-type (WT) and sfx mice (rescued by administering 500 mg of VC/L) were used as the control (WT) and treatment (MT) groups (n = 3 for each group), respectively. Total hepatic RNA was used in triplicate microarray assays for each group. EDGE software was used to identify differentially expressed genes and transcriptomic analysis was used to assess the potential genetic regulation of Gulo gene expression. Hepatic VC concentrations in MT mice were significantly lower than in WT mice, even though there were no morphological differences between the two groups. In MT mice, 269 differentially expressed transcripts were detected (≥ twice the difference between MT and WT mice), including 107 up-regulated and 162 down-regulated genes. These differentially expressed genes included stress-related and exclusively/predominantly hepatocyte genes. Transcriptomic analysis identified a major locus on chromosome 18 that regulates Gulo expression. Since three relevant oxidative genes are located within the critical region of this locus we suspect that they are involved in the down-regulation of oxidative activity in sfx mice.

Differential gene expression between wild-type and Gulo-deficient mice supplied with vitamin C

The aim of this study was to test the hypothesis that hepatic vitamin C (VC) levels in VC deficient mice rescued with high doses of VC supplements still do not reach the optimal levels present in wild-type mice. For this, we used a mouse scurvy model (sfx) in which the L-gulonolactone oxidase gene (Gulo) is deleted. Six age- (6 weeks old) and gender- (female) matched wild-type (WT) and sfx mice (rescued by administering 500 mg of VC/L) were used as the control (WT) and treatment (MT) groups (n = 3 for each group), respectively. Total hepatic RNA was used in triplicate microarray assays for each group. EDGE software was used to identify differentially expressed genes and transcriptomic analysis was used to assess the potential genetic regulation of Gulo gene expression. Hepatic VC concentrations in MT mice were significantly lower than in WT mice, even though there were no morphological differences between the two groups. In MT mice, 269 differentially expressed transcripts were detected (> twice the difference between MT and WT mice), including 107 up-regulated and 162 down-regulated genes. These differentially expressed genes included stress-related and exclusively/predominantly hepatocyte genes. Transcriptomic analysis identified a major locus on chromosome 18 that regulates Gulo expression. Since three relevant oxidative genes are located within the critical region of this locus we suspect that they are involved in the down-regulation of oxidative activity in sfx mice.