Insect mitochondrial genomes (mitogenomes) are of great interest in exploring molecular evolution, phylogenetics and population genetics. Only two mitogenomes have been previously released in the insect group Aphididae, which consists of about 5,000 known species including some agricultural, forestry and horticultural pests. Here we report the complete 16,317 bp mitogenome of Cavariella salicicola and two nearly complete mitogenomes of Aphis glycines and Pterocomma pilosum. We also present a first comparative analysis of mitochondrial genomes of aphids. Results showed that aphid mitogenomes share conserved genomic organization, nucleotide and amino acid composition, and codon usage features. All 37 genes usually present in animal mitogenomes were sequenced and annotated. The analysis of gene evolutionary rate revealed the lowest and highest rates for COI and ATP8, respectively. A unique repeat region exclusively in aphid mitogenomes, which included variable numbers of tandem repeats in a lineage-specific manner, was highlighted for the first time. This region may have a function as another origin of replication. Phylogenetic reconstructions based on protein-coding genes and the stem-loop structures of control regions confirmed a sister relationship between Cavariella and pterocommatines. Current evidence suggest that pterocommatines could be formally transferred into Macrosiphini. Our paper also offers methodological instructions for obtaining other Aphididae mitochondrial genomes.
Keeping mammalian gastrointestinal (GI) tract communities in balance is crucial for host health maintenance. However, our understanding of microbial communities in the GI tract is still very limited. In this study, samples taken from the GI tracts of C57BL/6 mice were subjected to 16S rRNA gene sequence-based analysis to examine the characteristic bacterial communities along the mouse GI tract, including those present in the stomach, duodenum, jejunum, ileum, cecum, colon and feces. Further analyses of the 283,234 valid sequences obtained from pyrosequencing revealed that the gastric, duodenal, large intestinal and fecal samples had higher phylogenetic diversity than the jejunum and ileum samples did. The microbial communities found in the small intestine and stomach were different from those seen in the large intestine and fecal samples. A greater proportion of Lactobacillaceae were found in the stomach and small intestine, while a larger proportion of anaerobes such as Bacteroidaceae, Prevotellaceae, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae were found in the large intestine and feces. In addition, inter-mouse variations of microbiota were observed between the large intestinal and fecal samples, which were much smaller than those between the gastric and small intestinal samples. As far as we can ascertain, ours is the first study to systematically characterize bacterial communities from the GI tracts of C57BL/6 mice.
Telomere reprogramming and silencing of exogenous genes have been demonstrated in mouse and human induced pluripotent stem cells (iPS cells). Pigs have the potential to provide xenotransplant for humans, and to model and test human diseases. We investigated the telomere length and maintenance in porcine iPS cells generated and cultured under various conditions. Telomere lengths vary among different porcine iPS cell lines, some with telomere elongation and maintenance, and others telomere shortening. Porcine iPS cells with sufficient telomere length maintenance show the ability to differentiate in vivo by teratoma formation test. IPS cells with short or dysfunctional telomeres exhibit reduced ability to form teratomas. Moreover, insufficient telomerase and incomplete telomere reprogramming and/or maintenance link to sustained activation of exogenous genes in porcine iPS cells. In contrast, porcine iPS cells with reduced expression of exogenous genes or partial exogene silencing exhibit insufficient activation of endogenous pluripotent genes and telomerase genes, accompanied by telomere shortening with increasing passages. Moreover, telomere doublets, telomere sister chromatid exchanges and t-circles that presumably are involved in telomere lengthening by recombination also are found in porcine iPS cells. These data suggest that both telomerase-dependent and telomerase-independent mechanisms are involved in telomere reprogramming during induction and passages of porcine iPS cells, but these are insufficient, resulting in increased telomere damage and shortening, and chromosomal instability. Active exogenes might compensate for insufficient activation of endogenous genes and incomplete telomere reprogramming and maintenance of porcine iPS cells. Further understanding of telomere reprogramming and maintenance may help improve the quality of porcine iPS cells.
Banana wilt disease, caused by the fungal pathogen Fusarium oxysporum f. sp. cubense 4 (Foc4), is regarded as one of the most devastating diseases worldwide. Cavendish cultivar ‘Yueyoukang 1’ was shown to have significantly lower disease severity and incidence compared with susceptible cultivar ‘Brazilian’ in greenhouse and field trials. De novo sequencing technology was previously performed to investigate defense mechanism in middle resistant ‘Nongke No 1’ banana, but not in highly resistant cultivar ‘Yueyoukang 1’. To gain more insights into the resistance mechanism in banana against Foc4, Illumina Solexa sequencing technology was utilized to perform transcriptome sequencing of ‘Yueyoukang 1’ and ‘Brazilian’ and characterize gene expression profile changes in the both two cultivars at days 0.5, 1, 3, 5 and 10 after infection with Foc4. The results showed that more massive transcriptional reprogramming occurs due to Foc4 treatment in ‘Yueyoukang 1’ than ‘Brazilian’, especially at the first three time points, which suggested that ‘Yueyoukang 1’ had much faster defense response against Foc4 infection than ‘Brazilian’. Expression patterns of genes involved in ‘Plant-pathogen interaction’ and ‘Plant hormone signal transduction’ pathways were analyzed and compared between the two cultivars. Defense genes associated with CEBiP, BAK1, NB-LRR proteins, PR proteins, transcription factor and cell wall lignification were expressed stronger in ‘Yueyoukang 1’ than ‘Brazilian’, indicating that these genes play important roles in banana against Foc4 infection. However, genes related to hypersensitive reaction (HR) and senescence were up-regulated in ‘Brazilian’ but down-regulated in ‘Yueyoukang 1’, which suggested that HR and senescence may contribute to Foc4 infection. In addition, the resistance mechanism in highly resistant ‘Yueyoukang 1’ was found to differ from that in middle resistant ‘Nongke No 1’ banana. These results explain the resistance in the highly resistant cultivar and provide more insights in understanding the compatible and incompatible interactions between banana and Foc4.
The moderate halophile Amycolicicoccus subflavus DQS3-9A1T is the type strain of a novel species in the recently described novel genus Amycolicicoccus, which was isolated from oil mud precipitated from oil produced water. The complete genome of A. subflavus DQS3-9A1T has been sequenced and is characteristic of harboring the genes for adaption to the harsh petroleum environment with salinity, high osmotic pressure, and poor nutrient levels. Firstly, it characteristically contains four types of alkane hydroxylases, including the integral-membrane non-heme iron monooxygenase (AlkB) and cytochrome P450 CYP153, a long-chain alkane monooxygenase (LadA) and propane monooxygenase. It also accommodates complete pathways for the response to osmotic pressure. Physiological tests proved that the strain could grow on n-alkanes ranging from C10 to C36 and propane as the sole carbon sources, with the differential induction of four kinds of alkane hydroxylase coding genes. In addition, the strain could grow in 1–12% NaCl with the putative genes responsible for osmotic stresses induced as expected. These results reveal the effective adaptation of the strain DQS3-9A1T to harsh oil environment and provide a genome platform to investigate the global regulation of different alkane metabolisms in bacteria that are crucially important for petroleum degradation. To our knowledge, this is the first report to describe the co-existence of such four types of alkane hydroxylases in a bacterial strain.
Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein–linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory.
Following oxygenation of arachidonic acid by cyclooxygenase to form prostaglandin H2 (PGH2), a variety of prostanoids can be generated with diverse physiologic effects on pain, inflammation, allergy, cardiovascular system, cancer, etc. To facilitate the quantitative analysis of prostanoids in human serum of cell culture, an ultra-high pressure LC (UHPLC)/MS/MS method was developed and validated for the measurement of six eicosanoids belonging to the cyclooxygenase pathway: PGE2, PGD2, 8-iso-PGF2α, PGF2α, 6-keto-PGF1α, and thromboxane B2 (TXB2). Selectivity, matrix effects, calibration model, precision, and accuracy (intraday and interday), lower limit of quantitation (LLOQ), recovery, stability, and sample dilution were evaluated. Fast UHPLC separation was carried out in only 0.5 min with isocratic elution, and each prostanoid was measured using negative electrospray ionization MS with collision-induced dissociation and selected reaction monitoring. UHPLC/MS/MS provided high throughput with peak widths of approximately 3 s and an LLOQ of 0.020 ng/mL for PGE2, 0.027 ng/mL for PGD2, 0.152 ng/mL for 8-iso-PGF2α, 0.179 ng/mL for PGF2α and 6-keto-PGF1α, and 0.013 ng/mL for TXB2.
Previously, we showed a mouse model (ACE8/8) of cardiac renin-angiotensin system (RAS) activation has a high rate of spontaneous ventricular tachycardia (VT) and sudden cardiac death (SCD) secondary to a reduction in connexin43 (Cx43) level. Angiotensin-II activation increases reactive oxygen species (ROS) production, and ACE8/8 mice show increased cardiac ROS. We sought to determine the source of ROS and if ROS played a role in the arrhythmogenesis.
Methods and Results
Wild-type and ACE8/8 mice with and without two weeks of treatment with L-NIO (nitric oxide synthase inhibitor), sepiapterin (precursor of tetrahydrobiopterin), MitoTEMPO (mitochondria-targeted antioxidant), TEMPOL (a general antioxidant), apocynin (NADPH oxidase inhibitor), allopurinol (xanthine oxidase inhibitor), and ACE8/8 crossed with P67 dominant negative mice to inhibit the NADPH oxidase were studied. Western blotting, detection of mitochondrial ROS by MitoSOX Red, electron microscopy, immunohistochemistry, fluorescent dye diffusion technique for functional assessment of Cx43, telemetry monitoring, and in-vivo electrophysiology studies were performed. Treatment with MitoTEMPO reduced SCD in ACE8/8 mice (from 74% to 18%, P<0.005), decreased spontaneous ventricular premature beats, decreased VT inducibility (from 90% to 17%, P<0.05), diminished elevated mitochondrial ROS to the control level, prevented structural damage to mitochondria, resulted in 2.6 fold increase in Cx43 level at the gap junctions, and corrected gap junction conduction. None of the other antioxidant therapies prevented VT and SCD in ACE8/8 mice.
Mitochondrial oxidative stress plays a central role in angiotensin II-induced gap junction remodeling and arrhythmia. Mitochondria-targeted antioxidants may be effective antiarrhythmic drugs in cases of RAS activation.
sudden cardiac death; ventricular tachycardia; oxidative stress; mitochondria
The full-genome sequence of the bluetongue virus serotype 1 (BTV-1) strain Y863, the first BTV-1 isolate of Eastern origin found in China, was determined. The virus was isolated from sheep during a severe outbreak of bluetongue in Shizhong County, Yunnan Province, southwest China, in 1979. The total size of the BTV-1 strain Y863 genome is 19,170 bp. Phylogenetic analyses demonstrate that it belongs to the major “Eastern” BTV topotype. The sequence information provided here will help in understanding the geographical origin and spread of this Chinese isolate of BTV-1, as well as aid in its comparison with global isolates of BTV-1 from sheep, cattle, and other host species origins.
Upon growth on n-hexadecane (C16), n-tetracosane (C24), and n-hexatriacontane (C36), Dietzia sp. strain DQ12-45-1b could produce different glycolipids, phospholipids, and lipopeptides. Interestingly, cultivation with C36 increased cell surface hydrophobic activity, which attenuated the negative effect of the decline of the emulsification activity. These results suggest that the mechanisms of biosurfactant production and cell surface hydrophobicity are dependent upon the chain lengths of the n-alkanes used as carbon sources.
Reactive Oxygen Species (ROS) generated by NADPH oxidase are generally known to be pro-inflammatory, and it seems to be counterintuitive that ROS play a critical role in regulating the resolution of the inflammatory response. However, we observed that deficiency of the p47phox component of NADPH oxidase in macrophages was associated with a paradoxical accentuation of inflammation in a whole animal model of non-infectious sepsis induced by endotoxin. We have confirmed this observation by interrogating four separate in vivo models that employ complementary methodology including the use of p47phox−/− mice, p47phox−/− bone marrow chimera mice, adoptive transfer of macrophages from p47phox−/− mice, and an isolated perfused lung edema model that all point to a relationship between excessive acute inflammation and p47phox deficiency in macrophages. Mechanistic data indicate that ROS deficiency in both cells and mice results in decreased production of IL-10 in response to treatment with LPS, at least in part, through attenuation of the Akt-GSK3-β signal pathway and that it can be reversed by the administration of recombinant IL-10. Our data support the innovative concept that generation of ROS is essential for counter-regulation of acute lung inflammation.
NADPH oxidase; p47phox; NF-kB; macrophage; endotoxin; sepsis
The complete genomic sequence of a bluetongue virus serotype 4 (BTV-4) strain (strain YTS-4), isolated from sentinel cattle in Yunnan Province, China, is reported here. This work is the first to document the complete genomic sequence of a BTV-4 strain from China. The sequence information will help determine the geographic origin of Chinese BTV-4 and provide data to facilitate future analyses of the genetic diversity and phylogenetic relationships of BTV strains.
Posterior pedicle screw fixation has become a popular method for treating thoracolumbar burst fractures. However, it remains unclear whether additional fusion could improve clinical and radiological outcomes. This meta-analysis was performed to evaluate the effectiveness of fusion as a supplement to pedicle screw fixation for thoracolumbar burst fractures.
MEDLINE, OVID, Springer, and Google Scholar were searched for relevant randomized and quasi-randomized controlled trials that compared the clinical and radiological efficacy of fusion versus nonfusion for thoracolumbar burst fractures managed by posterior pedicle screw fixation. Risk of bias in included studies was assessed using the Cochrane Risk of Bias tool. We generated pooled risk ratios or weighted mean differences across studies. Based on predefined inclusion criteria, 4 eligible trials with a total of 220 patients were included in this meta-analysis. The mean age of the patients was 35.1 years. 96.8% of the fractures were located at T12 to L1 level. Baseline characteristics were similar between the fusion and nonfusion groups. No significant difference was identified between the two groups regarding radiological outcome, functional outcome, neurologic improvement, and implant failure rate. The pooled data showed that the nonfusion group was associated with significantly reduced operative time (p<0.0001) and blood loss (p = 0.0003).
The results of this meta-analysis suggested that fusion was not necessary when thoracolumbar burst fracture was treated by posterior pedicle screw fixation. More randomized controlled trials with high quality are still needed in the future.
AIM: To explore effects of telomerase RNA-targeting phosphorothioate antisense oligodeoxynucleotides (PS-ASODN) on growth of human gastrointestinal stromal tumors transplanted in mice.
METHODS: A SCID mouse model for transplantation of human gastrointestinal stromal tumors (GISTs) was established using tumor cells from a patient who was diagnosed with GIST and consequently had been treated with imatinib. GIST cells cultured for 10 passages were used for inoculation into mice. Transfection of PS-ASODN was carried out with Lipotap Liposomal Transfection Reagent. GISTs that subsequently developed in SCID mice were subjected to intra-tumoral injection once daily from day 7 to day 28 post-inoculation, and mice were divided into the following four groups according to treatment: PS-ASODN group (5.00 μmoL/L of oligonucleotide, each mouse received 0.2 mL once daily); imatinib group (0.1 mg/g body weight); liposome negative control group (0.01 mL/g); and saline group (0.01 mL/g). On day 28, the mice were sacrificed, and tumor attributes including weight and longest and shortest diameters were measured. Tumor growth was compared between treatment groups, and telomerase activity was measured by enzyme-linked immunosorbent assay. Apoptosis was examined by flow cytometry. Real-time polymerase chain reaction was used to detect expression of the mRNA encoding the apoptosis inhibition B-cell leukemia/lymphoma 2 (bcl-2) gene.
RESULTS: In the PS-ASODN group, tumor growth was inhibited by 59.437%, which was markedly higher than in the imatinib group (11.071%) and liposome negative control group (2.759%) [tumor inhibition = (mean tumor weight of control group - mean tumor weight of treatment group)/(mean tumor weight of control group) × 100%]. Telomerase activity was significantly lower (P < 0.01) in the PS-ASODN group (0.689 ± 0.158) compared with the imatinib group (1.838 ± 0.241), liposome negative control group (2.013 ± 0.273), and saline group (2.004 ± 0.163). Flow cytometry revealed that the apoptosis rate of tumor cells treated with PS-ASODN was 20.751% ± 0.789%, which was higher (P < 0.01) than that of the imatinib group (1.163% ± 0.469%), liposome negative control group (1.212% ± 0.310%), and saline group (1.172% ± 0.403%). Expression of bcl-2 mRNA in the transplanted GISTs was markedly downregulated (P < 0.01) in the PS-ASODN group (7.245 ± 0.739) compared with the imatinib group (14.153 ± 1.618) and liposome negative control group (16.396 ± 1.351).
CONCLUSION: PS-ASODN can repress GIST growth, mediated perhaps by inhibition of telomerase activity and downregulation of bcl-2 expression.
Gastrointestinal stromal tumor; Phosphorothioate antisense oligonucleotides; Imatinib; Tumor inhibitory rate; Telomerase activity
AIM: To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF).
METHODS: Chinese experimental miniature swine were randomly divided into four groups (n = 7), and all animals were given D-galactosamine (D-gal) to induce ALF. Group A animals were then injected with 40 mL saline via the portal vein 24 h after D-gal induction; Group B animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h, 2 d and 4 d after D-gal induction; Group C received approximately 1 × 108 green fluorescence protein (GFP)-labeled MSCs (GFP-MSCs) suspended in 40 mL normal saline via the portal vein 24 h after D-gal induction; Group D animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h after D-gal induction, MSCs transplantation was then carried out at 24 h after D-gal induction, and finally 2 mg/kg IL-1Ra was injected via the ear vein 1 d and 3 d after surgery as before. Liver function, serum inflammatory parameters and pathological changes were measured and the fate of MSCs was determined.
RESULTS: The optimal efficiency of transfection (97%) was achieved at an multiplicity of infection of 80, as observed by fluorescence microscopy and flow cytometry (FCM). Over 90% of GFP-MSCs were identified as CD44+ CD90+ CD45- MSCs by FCM, which indicated that most GFP-MSCs retained MSCs characteristics. Biochemical assays, the levels of serum inflammatory parameters and histological results in Group D all showed a significant improvement in liver injury compared with the other groups (P < 0.05). The number of GFP-MSCs in Group D was also greater than that in Group B, and the long-term cell proliferation rate was also better in Group D than in the other groups.
CONCLUSION: MSCs transplantation is useful in ALF, IL-1Ra plays an important role in alleviating the inflammatory condition, and combination therapy with MSCs transplantation and IL-1Ra is a promising treatment for ALF.
Interleukin-1 receptor antagonist; Mesenchymal stem cells; Cell transplantation; Acute liver failure; Inflammatory environment
To investigate the knowledge, attitudes and practices (KAP) for dietary sodium intake among adult residents of Shandong Province, China
In 2011, we conducted a cross sectional survey among a representative sample of 15,350 adults aged 18 to 69 years using a standardized questionnaire to assess their KAP for sodium. Variation in the KAPs by gender, and residence location were compared using the Chi-square tests. Predictors for the ‘intention to’ and ‘currently taking action to’ reduce sodium intake were determined by multivariate logistic regression with adjustment for confounding factors.
KAPs for dietary sodium intake among urban residents was generally more favorable than among rural residents. Women were likely to have more favorable KAPs than men. About four fifth of subjects reported that they favored a low sodium diets. However, 31% reported that consumption of less sodium results in less physical strength. Overall, 70% indicated their intention to reduce sodium intake, although only 39 % reported that they had taken action to reduce sodium. Multiple logistic regression analyses indicated that favorable actions to dietary sodium reduction were more likely to occur among those who were aware of the link between sodium and hypertension, and less likely among those who had unfavorable attitudes towards dietary sodium reduction.
Increasing knowledge levels about the benefits of sodium reduction will be a key success factor for effective sodium reduction initiatives and is linked to favorable behavioral change. Emphasis should be placed on the rural area.
This study was designed to explore the relationship between obesity, diabetes mellitus (DM), and female breast cancer in Eastern China.
A 1:3 matched case–control study was carried out, comprising 123 women with breast cancer and 369 controls. All of the 492 subjects were selected from a previous epidemiological survey of 122,058 women in Eastern China.
There were significant differences between the case and control groups in waist circumference and body mass index (BMI), but not in waist to hip ratio or hip circumference. There was a significant difference between the two groups in BMI for post-menopausal women, and a significant difference in waist circumference for pre-menopausal women. After adjustment for other factors, BMI was still significantly associated with breast cancer (odds ratio (OR) = 1.58, 95% confidence interval (CI) 1.14 to 2.19). DM was significantly associated with breast cancer (OR = 3.35, 95% CI 1.02 to 11.01) in the univariate analysis but not in the multivariate analysis (P = 0.059).
Obesity might be a risk factor for female breast cancer. We found different strengths of association for women with different menopausal status when we examined the relationship between obesity and breast cancer. The association between DM and female breast cancer should be further confirmed with larger sample sizes.
Breast cancer; Female; Obesity; Diabetes mellitus; Case–control study
Objective: To evaluate the pharmacological effects of traditional Chinese medicine, bear bile capsule and Huangqi granule, on recurrent parotitis in children. Methods: In this prospective, controlled, and randomized study, a total of 151 young children were divided into three groups: Group A included massaging the children’s parotid region and melting vitamin C in their mouth daily; Group B included swallowing bear bile capsule and Huangqi granule daily; and Group C included massages and vitamin C as prescribed in Group A, and traditional Chinese medicine as prescribed in Group B. Children were treated individually for one month and then a follow-up study was conducted for 1 to 3.5 years. Analysis of variance (ANOVA) and Ridit analysis were employed for statistical analysis. Results: The recurrence rate decreased in every group, but was significantly more in Groups B and C when compared to Group A. The recurrences significantly decreased (P<0.01) in Group B and their recovery rate was as high as 63%, significantly better than those of the other groups (P<0.01). Conclusions: Huangqi and bear bile could be a novel clinical approach for treating recurrent parotitis in children.
Juvenile recurrent parotitis; Therapy; Pediatrics; Traditional Chinese medicine; Prospective study
Endothelial cells (ECs) form cell-cell adhesive junctional structures maintaining vascular integrity. This barrier is dynamically regulated by vascular endothelial growth factor (VEGF) receptor signaling. We created an inducible knockin mouse model to study the contribution of the integrin-associated focal adhesion tyrosine kinase (FAK) signaling on vascular function. Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation, rapid FAK localization to cell-cell junctions, binding of the FAK FERM domain to the vascular endothelial cadherin (VE-cadherin) cytoplasmic tail, and direct FAK phosphorylation of β-catenin at tyrosine-142 (Y142) facilitating VE-cadherin-β-catenin dissociation and EC junctional breakdown. Kinase inhibited FAK is in a closed conformation that prevents VE-cadherin association and limits VEGF-stimulated β-catenin Y142 phosphorylation. Our studies establish a role for FAK as an essential signaling switch within ECs regulating adherens junction dynamics.
FAK; VEGF; knockin mouse; vascular permeability; β-catenin
Pine wilt disease (PWD) caused by the pine wood nematode (PWN), Bursaphelenchus xylophilus, is one of the most devastating diseases of Pinus spp. The PWN was therefore listed as one of the most dangerous forest pests in China meriting quarantine. Virulence of the PWN is closely linked with the spread of PWD. However, main factors responsible for the virulence of PWNs are still unclear. Recently epiphytic bacteria carried by PWNs have drawn much attention. But little is known about the relationship between endophytic bacteria and virulence of B. xylophilus. In this research, virulence of ten strains of B. xylophilus from different geographical areas in six provinces of China and four pine species were tested with 2-year-old seedlings of Pinus thunbergii. Endophytic bacteria were isolated from PWNs with different virulence to investigate the relationship between the bacteria and PWN virulence. Meanwhile, the carbon metabolism of endophytic bacteria from highly and low virulent B. xylophilus was analyzed using Biolog plates (ECO). The results indicated that ten strains of PWNs showed a wide range of virulence. Simultaneously, endophytic bacteria were isolated from 90% of the B. xylophilus strains. The dominant endophytic bacteria in the nematodes were identified as species of Stenotrophomonas, Achromobacter, Ewingella, Leifsonia, Rhizobium, and Pseudomonas using molecular and biochemical methods. Moreover, S. maltophilia, and A. xylosoxidans subsp. xylosoxidans were the predominant strains. Most of the strains (80%) from P. massoniana contained either S. maltophilia, A. xylosoxidans, or both species. There was a difference between the abilities of the endophytic bacteria to utilize carbon sources. Endophytic bacteria from highly virulent B. xylophilus had a relatively high utilization rate of carbohydrate and carboxylic acids, while bacteria from low virulent B. xylophilus made better use of amino acids. In conclusion, endophytic bacteria widely exist in B. xylophilus from different pines and areas; and B. xylophilus strains with different virulence possessed various endophytic bacteria and diverse carbon metabolism which suggested that the endophytic bacteria species and carbon metabolism might be related with the B. xylophilus virulence.
pine wilt disease; Bursaphelenchus xylophilus; endophytic bacteria; virulence; Pinus massoniana; P. thunbergii.
The present study investigates a potential computational role of dynamical electrical synapses in neural information process. Compared with chemical synapses, electrical synapses are more efficient in modulating the concerted activity of neurons. Based on the experimental data, we propose a phenomenological model for short-term facilitation of electrical synapses. The model satisfactorily reproduces the phenomenon that the neuronal correlation increases although the neuronal firing rates attenuate during the luminance adaptation. We explore how the stimulus information is encoded in parallel by firing rates and correlated activity of neurons, and find that dynamical electrical synapses mediate a transition from the firing rate code to the correlation one during the luminance adaptation. The latter encodes the stimulus information by using the concerted, but lower neuronal firing rate, and hence is economically more efficient.
electrical synapses; short-term plasticity; information processing; adaptation; dynamical encoding
There are two widely used transient middle cerebral artery occlusion (MCAO) methods, which differ in the use of unilateral or bilateral carotid artery reperfusion (UNICAR and BICAR). Of the two methods, UNICAR is easier to perform. This study was designed to comprehensively compare the two reperfusion methods to determine if there are any differences in outcomes.
The UNICAR and BICAR groups each included 9 rats. At baseline, the average pO2 was 20.54 ± 9.35 and 26.43 ± 7.39, for the UNICAR and BICAR groups, respectively (P = 0.519). Changes in pO2, as well as other physiological parameters measured within the ischemic lesion, were similar between the UNICAR and BICAR groups during 90 min of MCAO and the first 30 min of reperfusion (all P > 0.05). Furthermore, both the Bederson score and Garcia score, which are used for neurological assessment, were also similar (both P > 0.05). There were also no significant differences in T2WI lesion volume, DWI lesion volume, PWI lesion volume, or TTC staining infarct volume between the two groups (all P > 0.05).
UNICAR and BICAR have similar capability for inducing acute brain ischemic injury and can be considered interchangeable up to 24 hours after reperfusion.
Middle cerebral artery occlusion; Ischemia; Reperfusion method; Bilateral Carotid reperfusion; Unilateral Carotid reperfusion; Neurological deficits; Diffusion weighted imaging; Perfusion weighted imaging; Partial oxygen pressure
A 59-year-old man underwent liver radiofrequency ablation under laparotomy for recurrent hepatic carcinoma located in the caudate lobe, however, near-fatal bleeding occurred 1 wk after the operation. The intra-operative ultrasound study during laparotomy revealed left hepatic artery pseudoaneurysm. Suture and packing with ribbon gauze was used to obtain hemostasis. A secondary hemorrhage followed 11 h later and hepatic angiography was performed immediately. Bleeding from the pseudoaneurysm in a branch of the left hepatic artery was found and the artery branch was embolized with coils. Other than slight bile leakage, post-embolization continued satisfactorily. Bleeding did not reoccur. The follow up visit 1 mo later found the pseudoaneurysm disappearing and no tumor recurrence.
Hepatocellular carcinoma; Radiofrequency ablation; Complication; Hepatic angiography; Embolization
Kinase-inhibited FAK limits VCAM-1 production via nuclear localization and promotion of GATA4 turnover.
Vascular cell adhesion molecule–1 (VCAM-1) plays important roles in development and inflammation. Tumor necrosis factor–α (TNF-α) and focal adhesion kinase (FAK) are key regulators of inflammatory and integrin–matrix signaling, respectively. Integrin costimulatory signals modulate inflammatory gene expression, but the important control points between these pathways remain unresolved. We report that pharmacological FAK inhibition prevented TNF-α–induced VCAM-1 expression within heart vessel–associated endothelial cells in vivo, and genetic or pharmacological FAK inhibition blocked VCAM-1 expression during development. FAK signaling facilitated TNF-α–induced, mitogen-activated protein kinase activation, and, surprisingly, FAK inhibition resulted in the loss of the GATA4 transcription factor required for TNF-α–induced VCAM-1 production. FAK inhibition also triggered FAK nuclear localization. In the nucleus, the FAK-FERM (band 4.1, ezrin, radixin, moesin homology) domain bound directly to GATA4 and enhanced its CHIP (C terminus of Hsp70-interacting protein) E3 ligase–dependent polyubiquitination and degradation. These studies reveal new developmental and anti-inflammatory roles for kinase-inhibited FAK in limiting VCAM-1 production via nuclear localization and promotion of GATA4 turnover.