Differential contributions of G protein- or arrestin subtype-mediated signalling underlie urocortin 3-induced somatostatin secretion in pancreatic δ cells.

BACKGROUND AND PURPOSE: Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic ß cells activates the CRF2 receptor (CRF2R) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis. EXPERIMENTAL APPROACH: Here, we used Arrb1-/-, Arrb2-/-, Gsfl/fl and Gqfl/fl knockout mice, the G11-shRNA-GFPfl/fl lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of Gs, G11 and ß-arrestin1 to CRF2R contributed to UCN3-induced SST secretion in pancreatic δ cells. KEY RESULTS: Our study showed that CRF2R coupled to a panel of G protein and arrestin subtypes in response to UCN3 engagement. While RyR3 phosphorylation by PKA at the S156, S2706 and S4697 sites may underlie the Gs-mediated UCN3- CRF2R axis for SST secretion, the interaction of SYT1 with ß-arrestin1 is also essential for efficient SST secretion downstream of CRF2R. The specific expression of the transcription factor Stat6 may contribute to G11 expression in pancreatic δ cells. Furthermore, we found that different UCN3 concentrations may have distinct effects on glucose homeostasis, and these effects may depend on different CRF2R downstream effectors. CONCLUSIONS AND IMPLICATIONS: Collectively, our results provide a landscape view of signalling mediated by different G protein or arrestin subtypes downstream of paracrine UCN3- CRF2R signalling in pancreatic ß-δ-cell circuits, which may facilitate the understanding of fine-tuned glucose homeostasis networks.

Correlation Between Lipoprotein-Related Phospholipase A2 and Metabolic Syndrome.

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been recognized as a valuable biomarker for identifying the risk of cardiovascular diseases and inflammation. Furthermore, there is strong evidence to suggest that metabolic syndrome is closely associated with chronic inflammation. Accordingly, the present study endeavors to examine the potential correlation between metabolic syndrome and the levels of Lp-PLA2. Methods: To explore the relationship between Lp-PLA2 levels and metabolic syndrome, and to establish the predictive cut-off value of Lp-PLA2, a retrospective analysis was conducted using medical data from a sample of 3549 Chinese adults (comprising 2182 men and 1367 women) aged between 18 and 50 years, who had undergone health check-ups. In addition, the study also sought to investigate any potential differences in Lp-PLA2 levels based on sex and age. Results: The analysis of the data indicated that participants had a mean age of 44.2 years, a mean Lp-PLA2 level of 589 IU/L, and a metabolic syndrome prevalence of 22%. Lp-PLA2 levels were significantly different between males and females, and a significant correlation was observed between Lp-PLA2 levels and clinical and metabolic characteristics, including BMI, cholesterol, and triglycerides. Interestingly, Lp-PLA2 demonstrated potential as an indicator of metabolic syndrome, particularly in females, despite other biomarkers, such as TG/HDL-C and WHR, exhibiting better area under the curve. Conclusion: Our findings suggest that Lp-PLA2 may serve as a useful biomarker for identifying individuals at risk of developing metabolic syndrome, particularly in females. Further research is needed to explore the potential of Lp-PLA2 as a diagnostic and therapeutic target for metabolic syndrome.

Predicting the outcomes of hepatocellular carcinoma downstaging with the use of clinical and radiomics features.

BACKGROUND: Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. METHODS: Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. RESULTS: Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. CONCLUSIONS: The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.

Oxygen Challenge Imaging Reveals Differences in Metabolic Activity Between Kurtosis Lesion and Diffusion/Kurtosis Lesion Mismatch in a Rodent Model of Acute Stroke.

OBJECTIVE: Accurate identification of potentially salvageable tissues is critical for improving acute stroke treatment. A previous study showed that the kurtosis lesion exhibited insignificant response after prompt reperfusion treatment, while the diffusion/kurtosis lesion mismatch could recover after reperfusion. We hypothesized that these 2 regions are in different metabolic states. MATERIALS AND METHODS: Transient oxygen challenge (OC) is a procedure that uses oxygen as a metabolic bio-tracer and has been performed to explore metabolic activity in tissues. We combined OC with multiparameter magnetic resonance imaging (including diffusion kurtosis imaging and T2* mapping sequences) to study metabolic activity in the ischemic brain of Sprague Dawley rats. RESULTS: Oxygen challenge image analysis revealed changes in T2* values, most significantly in the mean diffusivity (MD)/mean kurtosis (MK) lesion mismatch (22.3 ± 1.6%) and least significantly in the MK lesions (6.6 ± 0.6%). The MD images acquired within 138 ± 9 minutes after ischemia showed a larger ischemic lesion (45.5 ± 3.0% of the total area) than the MK images (33.2 ± 4.2% of the total area). The change rate of the MK value (53.0 ± 4.4%) was higher than that of the MD value (37.5 ± 3.2%). CONCLUSIONS: The present study shows that MK lesion and MD/MK lesion mismatch exhibited different metabolic activity states. The MK lesion presented metabolic-related values close to the ischemic core, while at least part of the MD/MK mismatch area was comparable with ischemic penumbra metabolic activity. These findings are important to support image-guided individualized stroke therapies.

How does information overload about COVID-19 vaccines influence individuals' vaccination intentions? The roles of cyberchondria, perceived risk, and vaccine skepticism.

This research proposes and tests an integrated model to explain how information overload influence vaccine skepticism and vaccination intention. In addition, this research investigates the effectiveness of using a celebrity endorsement strategy in promoting vaccination and compares its effectiveness with other endorsement types. A survey study (Study 1) was conducted to examine the mechanism underlying the impact of the COVID-19 vaccine information overload on vaccine skepticism that, subsequently, affects vaccination intention. It also examined the moderating role of celebrity endorsement trustworthiness. The results indicate that information overload positively influenced vaccine skepticism through cyberchondria and perceived risk of the vaccine, which subsequently reduces vaccination intention. The negative effect of vaccine skepticism on vaccination intention was weakened by the celebrity endorsement that was considered trustworthy. A follow-up experimental study (Study 2) was performed to compare the effectiveness of celebrity endorsement with other endorsement types (i.e., government official and medical expert endorsements). The results showed that the celebrity endorsement was more effective in mitigating the negative effect of vaccine skepticism on vaccination intention compared to government official and medical expert. The findings provide practical insights into how governments can minimize people's vaccine skeptical views and increase their vaccination intentions.

Enhancing dieters' perseverance in adversity: How counterfactual thinking increases use of digital health tracking tools.

OBJECTIVES: Dieting is a cognitively taxing task that does not always advance well-being. A dieting lapse may result in overconsumption that undermines long-term health goals. This research explores how a process known as counterfactual thinking (CFT), reliving an event to figure out where things went wrong, may help consumers faced with a temptation to indulge. Consumers who engage in upward CFT generate an alternative set of steps or actions that could have changed the outcome in a situation. We investigate if and how CFT may be used strategically to help consumers stick to their dieting goal and advance their own well-being. METHODS: A 2 (CFT vs. control) x 2 (dieter vs. non-dieter) between-subjects factorial design was used to evaluate participant interest in a digital health tracking tool after viewing an advertisement (Study 1). Study 2 was conducted as a follow-up to measure their use of the digital tracking tool, intentions to continue to use, and calories consumed (as tracked in the system) after a two-week period using the digital tracking tool advertised in Study 1. RESULTS: We find that engaging in upward CFT increases a dieter's intentions to track their food, a practice emerging as a strategy to help maintain goal consistency. Among dieters, perceived feasibility mediated the impact of CFT on both ad evaluations (Study 1) as well as intentions to continue to use the digital health tracking tool (Study 2). In the follow-up study we also find that dieters in the CFT condition used more of the online features offered and that all consumers in the CFT condition ate marginally fewer calories across two weeks of tracking using the digital health tool. DISCUSSION: Encouraging consumers to generate upward counterfactual thoughts in the face of a dieting lapse increases their propensity to use an online tracking tool and reduces calories consumed. In the age of digital tracking tools, personalized prompts could be set to encourage CFT to help get a consumer back on track to pursue their healthy eating goals.

Comparative Study of Amide Proton Transfer-Weighted Imaging and Intravoxel Incoherent Motion Imaging in Breast Cancer Diagnosis and Evaluation.

BACKGROUND: Amide proton transfer-weighted imaging (APTWI) and intravoxel incoherent motion imaging (IVIM) are valuable MRI techniques applied to cancer. PURPOSE: To compare APTWI and IVIM in the diagnosis of benign and malignant breast lesions and to evaluate the correlations between different parameters (MTRasym [3.5 ppm], D, D*, and f) and prognostic factors for breast cancer. STUDY TYPE: Retrospective. POPULATION: In all, 123 breast lesions were studied before treatment, including 58 benign lesions and 65 malignant lesions. FIELD STRENGTH/SEQUENCE: Conventional MRI (T1 WI, T2 WI, and diffusion-weighted imaging [DWI]), APTWI, and IVIM MRI at 3T. ASSESSMENT: The magnetization transfer ratio asymmetry at 3.5 ppm (MTRasym [3.5 ppm]), diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) values were compared between the benign and malignant groups and between groups with different expression levels of prognostic factors. STATISTICAL TESTS: Individual sample t-test, χ2 test, Spearman correlation, logistic regression, and the Delong test. RESULTS: The D and MTRasym (3.5 ppm) values of the malignant group were lower than those of the benign group; however, D* and f values were higher than those of the benign group (all P < 0.05). The areas under the curve (AUCs) of D, MTRasym (3.5 ppm), D*, and f were 0.809, 0.778, 0.670, and 0.766, respectively; however, only the difference between AUC (D) and AUC (D*) was significant (Z = 2.374, P < 0.05). The D value showed a low correlation with the pathological grade and Ki-67 expression (| r | = 0.294, 0.367); the f value showed a low correlation with estrogen receptor (ER) expression (| r | = 0.382); and the MTRasym (3.5 ppm) value showed a low correlation with pathological grade (| r | = 0.371). DATA CONCLUSION: This analysis revealed that both IVIM and APTWI could be used for the differential diagnosis of benign and malignant breast lesions, and APTWI-derived MTRasym (3.5 ppm), IVIM-derived D, D*, and f values showed correlations with some prognostic factors for breast cancer. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:1175-1186.

Pathological and immunological analyses of Thelohanellus kitauei (Myxozoa:Myxosporea) infection in the scattered mirror carp, Cyprinus carpio.

Thelohanellus kitauei is a spore-forming myxosporean parasite prevalent in scattered mirror carp (Cyprinus carpio) that generates numerous cysts in the intestine and causes mass mortality in fish. To investigate the infection and mortality induced by T. kitauei in pond-reared farms in Luo-Jiang (104°51'N, 31°31'E), southwest China, morphological and molecular analyses of infected fish were conducted. Natural and specific immune indicators were further evaluated to determine the immunological effects of response to parasitic infection. The infectious parasite was identified as Thelohanellus kitauei based on morphological, 18S rDNA and infectious characteristics. Scattered mirror carp was determined as the specific intermediate host of the parasite. However, T. kitauei still caused considerable damage to the fish, in particular, injury and blockage of the intestines, resulting in malnutrition and even death. The mature spores of T. kitauei colonize the intestinal submucosa of carp and form cysts of various sizes that block the intestinal tract and release spores into the enteric cavity upon rupture, leading to the next phase of T. kitauei growth. Moreover, T. kitauei-infected carp showed weaker innate immunity. IgM is involved in the fight against parasitic infection while cytokines, such as IL-6, IL-1ß and TNF-α, had an impact on infection processes. To our knowledge, this is the first report to show that T. kitauei infects and causes death in scattered mirror carp. Our collective findings from systematic pathology, morphology and immunology experiments provide a foundation for further research on infections by this type of parasite and development of effective treatment strategies.

Population structure and transmission modes of indigenous typhoid in Taiwan.

BACKGROUND: Indigenous typhoid fever was continuing to be identified in Taiwan which has not been endemic for the enteric fever for more than 20 years. The source and transmission by which the local patients acquired typhoid and the population structure of the indigenous typhoid strains remain not well characterized. METHODS: During 2001 and 2014, non-duplicated clinical Salmonella enterica serovar Typhi isolates in a hospital were analyzed by whole-genome sequencing (WGS) and determined for pulsotypes. Maximum likelihood phylogeny was constructed by nucleotide alterations in core genomes and compared to the framework of global typhoid strains. Potential source and transmission were traced by correlating the phylogeny and the temporal relationship between isolates. RESULTS: A total of 43 S. Typhi isolates from indigenous cases were analyzed and a majority (39, 90.7%) of them were belonged to six WGS-defined genotypes prevailing mainly in Southeast Asia. Genotype 3.4.0 and a multidrug-resistant type 4.3.1 (also known as pandemic H58 haplotype) were associated respectively with two solitary small-scale outbreaks, implying a transmission mode of importation followed by outbreak. Twelve isolates with nearly identical core genomes were belonged to genotype 3.2.1 but were categorized into three different pulsotypes. The 3.2.1 isolates were identified across 13 years and involved in three clusters and a sporadic case, indicating sustained local transmission of the same strain. The remaining indigenous isolates belonging to three genotypes (2.1, 3.1.2, and 3.0.0) were of substantial genetic diversity and isolated at different time points, indicating independent event of each case. CONCLUSIONS: Indigenous typhoid in Taiwan occurred mainly with the forms of small-scale outbreaks or sporadic events likely by contracting imported strains which prevailed in Southeast Asia. Sustained local transmission of certain strain was also evident by WGS analysis, but not by conventional pulsotyping, highlighting the importance of continuing molecular surveillance of typhoid fever with adequate tools in the non-endemic region.

A Yersinia ruckeri TIR Domain-Containing Protein (STIR-2) Mediates Immune Evasion by Targeting the MyD88 Adaptor.

TIR domain-containing proteins are essential for bacterial pathogens to subvert host defenses. This study describes a fish pathogen, Yersinia ruckeri SC09 strain, with a novel TIR domain-containing protein (STIR-2) that affects Toll-like receptor (TLR) function. STIR-2 was identified in Y. ruckeri by bioinformatics analysis. The toxic effects of this gene on fish were determined by in vivo challenge experiments in knockout mutants and complement mutants of the stir-2 gene. In vitro, STIR-2 downregulated the expression and secretion of IL-6, IL-1ß, and TNF-α. Furthermore, the results of NF-κB-dependent luciferase reporter system, co-immunoprecipitation, GST pull-down assays, and yeast two-hybrid assay indicated that STIR-2 inhibited the TLR signaling pathway by interacting with myeloid differentiation factor 88 (MyD88). In addition, STIR-2 promoted the intracellular survival of pathogenic Yersinia ruckeri SC09 strain by binding to the TIR adaptor protein MyD88 and inhibiting the pre-inflammatory signal of immune cells. These results showed that STIR-2 increased virulence in Y. ruckeri and suppressed the innate immune response by inhibiting TLR and MyD88-mediated signaling, serving as a novel strategy for innate immune evasion.

Elizabethkingia miricola infection in Chinese spiny frog (Quasipaa spinosa).

Elizabethkingia miricola is a Gram-negative rod which has been incriminated in severe infections in humans. Recently, a serious infectious disease was identified in Chinese spiny frogs (Quasipaa spinosa), in the Sichuan Province of China; the disease was characterized by corneal opacity, the presence of ascites and neurological symptoms. A Gram-negative bacillus was isolated from the liver, spleen and kidney of the diseased frogs. Experimental infection test revealed that the bacillus could infect the frogs Q. spinosa and the LD50 value was 1.19 × 106  cfu per frog. The isolated Gram-negative bacillus was identified as E. miricola according to phenotypic characteristics, 16S rRNA and gyrB gene sequence analysis. The isolated strain was only susceptible to florfenicol among all investigated chemotherapeutic agents. Histological examination revealed that E. miricola infection caused pathological lesions to multiple organs and tissues, especially in the liver, brain, kidney. These results confirmed that E. miricola is an emerging pathogen of Chinese spiny frogs.

Acute and Subacute toxicity study of Olaquindox by feeding to common carp (Cyprinus carpio L.).

Olaquindox, is a growth-promoting feed additive for food-producing animals. As the banned medicinal feed additive, olaquindox in animal feed and water must be concerned as an important hazard index. To improve studies of the toxicity of olaquindox, we provide a toxicological effects of olaquindox on a common freshwater fish, Cyprinus carpio L. The results of acute toxicity tests showed that the 7d-LD50 of olaquindox administered by feeding for common carp was determined to be 3746.3 mg/kg. We also found that the accumulation coefficient of olaquindox in carp was 1.45-1.9. Based on the studied hematological and blood biochemical parameters (RBCs count, hemoglobin content, ALT, AST and SOD activity), we found that olaquindox induced significant alterations in all studied parameters. Regarding bioaccumulation, the results showed that olaquindox had more efficiency to internalize fish tissues (liver, kidneys and muscle). The histopathological investigation of tissues from poisoning fish revealed various alterations that varied between adaptation responses and permanent tissue damage. Our results indicate that olaquindox are toxic to common carp and have obvious accumulation, and all the data from acute and subacute toxicity experiments in common carp may provide a useful tool for assessing the toxicity of olaquindox to aquatic organisms.

Hepatoprotective potential of isoquercitrin against type 2 diabetes-induced hepatic injury in rats.

Non-alcoholic fatty liver disease is a main complication of type 2 diabetes. Isoquercitrin are employed for antidiabetic therapies, but the effects on liver function and the hepatocytes are unclear. The aim of this study was to investigate the effects of isoquercitrin on the T2DM-induced hepatic injury in rats. Isoquercitrin (10 mg/kg/d, 30 mg/kg/d), sitagliptin phosphate (10 mg/kg/d) was given orally for 21 days. The administration of isoquercitrin at 10 mg/kg/d and 30 mg/kg/d showed a dose dependent. Compare to the negative control (treated with saline), rats medicated with isoquercitrin (30 mg/kg/d) and sitagliptin phosphate (10 mg/kg/d) improved the clinical symptoms, FBG and glucose tolerance, reduced serum ALT, AST and IR, but increased TP, Alb, SOD, GSH, MDA, HDL-C, INS and GLP-1. On histology, Rats of these to groups presented nearly normal liver tissue and Langerhans, degeneration, necrosis and apoptosis were markedly reduced. Instead, hepatocytes showed regenerate. These two groups also showed significant increase in mRNA expression of PKA, AKT, PKCa, InsR and PI3K, and a decrease in DPP-IV mRNA level. These results indicated that treatment with isoquercitrin protects against hepatic injury by T2DM.

Multidrug-Resistant Aeromonas veronii Recovered from Channel Catfish (Ictalurus punctatus) in China: Prevalence and Mechanisms of Fluoroquinolone Resistance.

To emphasize the importance of the appropriate use of antibiotics in aquaculture systems, the prevalence of resistance to 25 antimicrobials was investigated in 42 Aeromonas veronii strains isolated from farm-raised channel catfish in China in 2006-2012. All experiments were based on minimal inhibitory concentrations (MICs), and susceptibility was assessed according to the Clinical and Laboratory Standards Institute. Some isolates displayed antibiotic resistance to the latest-generation fluoroquinolones (i.e., ciprofloxacin, levofloxacin, and norfloxacin) in vitro. Therefore, we screened for genes conferring resistance to fluoroquinolones and performed conjugation experiments to establish the resistance mechanisms. The antibiotic resistance rates were 14.29-21.42% to three kinds of fluoroquinolones: ciprofloxacin, levofloxacin, and norfloxacin. Among the 42 strains isolated, 15 carried the qnrS2 gene. The MICs of the fluoroquinolones in transconjugants with qnrS2 were more than fourfold higher compared with the recipient. Among the fluoroquinolone-resistant A. veronii strains, eight had point mutations in both gyrA codon 83 (Ser83→Ile83) and parC codon 87 (Ser87→Ile87). However, five isolates with point mutations in parC codon 52 remained susceptible to the three fluoroquinolones. In conclusion, the mechanisms of fluoroquinolone resistance in A. veronii isolates may be related to mutations in gyrA codon 83 and parC codon 87 and the presence of the qnrS2 gene.

OmpN, outer membrane proteins of Edwardsiella ictaluri are potential vaccine candidates for channel catfish (Ictalurus punctatus).

Outer membrane proteins (OMPs) are a class of proteins that reside in the outer membrane of Gram-negative bacteria. OMPs act as epitopes and are potential vaccine candidates. Outer membrane protein N (OmpN) is a component of the outer membrane of Edwardsiella ictaluri (E. ictaluri). In a previous study, the OmpN1-, OmpN2-, OmpN3-encoding genes of E. ictaluri were cloned, and here they were expressed in Escherichia coli. Western blotting showed that these three proteins had molecular weights of ∼60kDa. Channel catfish were immunized with recombinant OmpNs (rOmpNs) and then challenged with E. ictaluri. The results showed that rOmpN1, rOmpN2, and rOmpN3, as well as a mixture of all three proteins (in a ratio of 1:1:1) generated moderate immune protection (relative percentage of survival=62.5, 62.5, 67.5, and 75%, respectively). In an agglutination antibody titer assay, fish antisera showed an antibody titer of 1:128. Furthermore, each of the proteins stimulated high levels of lysozyme activity. In addition, a real-time polymerase chain reaction analysis revealed significant up-regulation of immune-related genes encoding major histocompatibility complex class I (MHC I), MHC II, CD4L, tumor necrosis factor-α, and interferon-γ after 24 and 48h of challenge, compared with the levels stimulated by phosphate-buffered saline. Taken together, we conclude that rOmpNs may elicit immune responses and generate protection against E. ictaluri in channel catfish. Thus, rOmpNs could be promising vaccine candidates against E. ictaluri.

cpsJ gene of Streptococcus iniae is involved in capsular polysaccharide synthesis and virulence.

The capsular polysaccharides are an important virulence factor of Streptococcus iniae, protecting the bacterium from destruction and clearance by the immune system. The cpsJ gene encodes a putative UDP-glucose epimerase involved in the capsule synthesis system. To determine the role of the CpsJ protein in the production of the capsule, a ΔcpsJ mutant was generated and analyzed by comparing its growth performances and virulence with those of the wild type (WT) strain. The ΔcpsJ mutant had longer chains, smaller colonies, and a slower growth rate and decreased optical density than the WT, suggesting that the ΔcpsJ mutant produces less capsular polysaccharide. The ΔcpsJ mutant was more able to adhere to and invaded epithelioma papulosum cyprinid cells (EPCs) when its virulence in vitro was compared with that of the WT, but survived less well in the whole blood of channel catfish. When a channel catfish infection model was used to determine the virulence of the ΔcpsJ mutant in vivo, the mutant caused an increase in survival with the mutant (53.33 %) versus the WT (26.67 %). In summary, mutation of the cpsJ gene influenced both the capsule synthesis and virulence of S. iniae.

Genome Sequence of the Fish Pathogen Yersinia ruckeri SC09 Provides Insights into Niche Adaptation and Pathogenic Mechanism.

Yersinia ruckeri is the etiologic agent of enteric red mouth disease (ERM), a severe fish disease prevailing in worldwide aquaculture industries. Here we report for the first time the complete genome of Y. ruckeri (Yersinia ruckeri) SC09, a highly virulent strain isolated from Ictalurus punctatus with severe septicemia. SC09 possesses a single chromosome of 3,923,491 base pairs, which contains 3651 predicted protein coding sequences (CDS), 19 rRNA genes, and 79 tRNA genes. Among the CDS, we have identified a Ysa locus containing genes encoding all the components of a type III secretion system (T3SS). Comparative analysis suggest that SC09-Ysa share extensive similarity in sequence, gene content, and gene arrangement with Salmonella enterica pathogenicity island 1 (SPI1) and chromosome-encoded T3SS from Yersinia enterocolitica biotype 1B. Furthermore, phylogenetic analysis shown that SC09-Ysa and SPI1-T3SS belong on the same branch of the phylogenetic tree. These results suggest that SC09-Ysa and SPI1-T3SS appear to mediate biological function to adapt to specific hosts with a similar niche, and both of them are likely to facilitate the development of an intracellular niche. In addition, our analysis also indicated that a substantial part of the SC09 genome might contribute to adaption in the intestinal microenvironment, including a number of proteins associated with aerobic or anaerobic respiration, signal transduction, and various stress reactions. Genomic analysis of the bacterium offered insights into the pathogenic mechanism associated with intracellular infection and intestinal survivability, which constitutes an important first step in understanding the pathogenesis of Y. ruckeri.

Ultrastructural Changes of Brain Tissues Surrounding Hematomas after Intracerebral Hemorrhage.

Our knowledge about pathophysiology of intracerebral hemorrhage (ICH) mainly originates from preclinical models of ICH. In this study, cerebral ultrastructure surrounding hematoma and its correlation with clinical severity were investigated in ICH patients. Thirty patients with basal ganglia hemorrhage and 6 control subjects were enrolled. Surgical evacuation was performed for patients with a blood loss >30 ml. Stroke severity was assessed using the Glasgow Coma Scale (GCS) and the National Institute of Health Stroke Scale (NIHSS). Transmission electron microscopy (TEM) was used to evaluate the ultrastructural characteristics of tissue specimens. Neural cells surrounding the hematomas showed evidence of cell swelling and necrosis. Decreased numbers of organelles and mitochondrial cristae were accompanied by cytoplasmic vacuolization, nuclear membrane invagination and breakdown, and intranuclear chromatic agglutination. These changes resulted in disintegration together with malacia, disappearance of the nucleus and nucleolus, and karyopyknosis. More serious ultrastructural damage was seen in patients with greater NIHSS scores, lower GCS scores, and greater bleeding volumes (p < 0.001). These findings suggest that neural cells undergo unfavorable ultrastructural changes that are responsible for dysfunction after ICH.

Complete Genome Sequence of the Fish Pathogen Yersinia ruckeri Strain SC09, Isolated from Diseased Ictalurus punctatus in China.

Yersinia ruckeri SC09 is a Gram-negative bacterium isolated from a moribund Ictalurus punctatus collected in Jianyang, China. Here, we report the complete genome sequence of this microorganism to facilitate the investigation of its pathogenicity and to reevaluate its taxonomic position.

A recombinant truncated surface immunogenic protein (tSip) plus adjuvant FIA confers active protection against Group B streptococcus infection in tilapia.

PURPOSE: Tilapia is an important agricultural fish that has been plagued by Group B streptococcus (GBS) infections in recent years, some of them severe. It is well-known that surface immunogenicity protein (Sip) is an effective vaccine against GBS. EXPERIMENTAL DESIGN: Since Sip was not expressed in either E. coli BL21 or E. coli Rosetta, we removed the N-terminal signal peptide and LysM of the virus to produce purified truncated Sip (tSip(1)), which multiplied easily in an E. coli host. The antibody's ability to recognize and combine with GBS was determined by Western-blot and specific staining in vitro. The relative percentage of survival (RPS), antibody titers, bacterial recovery, and pathologic morphology were monitored in vivo to evaluate the immune effects. Freund's incomplete adjuvant (FIA) plus tSip and aluminum hydroxide gel (AH) plus tSip were also evaluated. RESULTS: It revealed that tSip mixed with FIA was an effective vaccine against GBS in tilapia, while AH is toxic to tilapia.