Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3 draft genome sequence of 'SunUp' papaya, the ...first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties.
Obsessive-compulsive disorder (OCD) has been associated with abnormal cognitive and emotional functions and these dysfunctions may be dependent on the disruption of dynamic interactions within ...neuronal circuits associated with emotion regulation. Although several studies have shown the aberrant cognitive-affective processing in OCD patients, little is known about how to characterize effective connectivity of the disrupted neural interactions. In the present study, we applied effective connectivity analysis using dynamic causal modeling to explore the disturbed neural interactions in OCD patients.
A total of 20 patients and 21 matched healthy controls performed a delayed-response working memory task under emotional or non-emotional distraction while undergoing functional magnetic resonance imaging.
During the delay interval under negative emotional distraction, both groups showed similar patterns of activations in the amygdala. However, under negative emotional distraction, the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) exhibited significant differences between groups. Bayesian model averaging indicated that the connection from the DLPFC to the OFC was negatively modulated by negative emotional distraction in patients, when compared with healthy controls (p < 0.05, Bonferroni-corrected).
Exaggerated recruitment of the DLPFC may induce the reduction of top-down prefrontal control input over the OFC, leading to abnormal cortico-cortical interaction. This disrupted cortico-cortical interaction under negative emotional distraction may be responsible for dysfunctions of cognitive and emotional processing in OCD patients and may be a component of the pathophysiology associated with OCD.
Summary
Hepatitis B virus x protein (HBX), a product of hepatitis B virus (HBV), is a multifunctional protein that regulates viral replication and various cellular functions. Recently, HBX has been ...shown to induce autophagy; however, the responsible mechanism is not fully known. In this study, we established stable HBX‐expressing epithelial Chang cells as the platform to study how HBX induced autophagy. The results showed that the overexpression of HBX resulted in starvation‐induced autophagy. HBX‐induced autophagy was related to its ability to dephosphorylate/activate death‐associated protein kinase (DAPK). The block of DAPK by its siRNA significantly counteracted HBX‐mediated autophagy, confirming the positive role of DAPK in this process. HBX also induced Beclin 1, which functions at the downstream of the DAPK‐mediated autophagy pathway. Although HBX could activate JNK, a kinase known to participate in autophagy in certain conditions, the change in JNK failed to influence HBX‐induced autophagy. In conclusion, HBX induces autophagy via activating DAPK in a pathway related to Beclin 1, but not JNK. This new finding should help us to understand the role of autophagy in HBX‐mediated pathogenesis and thus may provide targets for intervening HBX‐related disorders.
Five pentacyclic triterpenoids isolated from Campsis grandiflora were tested for insulin-mimetic and insulin-sensitizing activity. The compounds enhanced the activity of insulin on tyrosine ...phosphorylation of the IR (insulin receptor) beta-subunit in CHO/IR (Chinese-hamster ovary cells expressing human IR). Among the compounds tested, CG7 (ursolic acid) showed the greatest enhancement and CG11 (myrianthic acid) the least. We characterized the effect of CG7 further, and showed that it acted as an effective insulin-mimetic agent at doses above 50 mug/ml and as an insulin-sensitizer at doses as low as 1 mug/ml. Additional experiments showed that CG7 increased the number of IRs that were activated by insulin. This indicates that a major mechanism by which CG7 enhances total IR auto-phosphorylation is by promoting the tyrosine phosphorylation of additional IRs. CG7 not only potentiated insulin-mediated signalling (tyrosine phosphorylation of the IR beta-subunit, phosphorylation of Akt and glycogen synthase kinase-3beta), but also enhanced the effect of insulin on translocation of glucose transporter 4 in a classical insulin-sensitive cell line, 3T3-L1 adipocytes. The results of the present study demonstrate that a specific pentacyclic triterpenoid, CG7, exerts an insulin-sensitizing effect as an IR activator in CHO/IR cells and adipocytes. The enhancement of insulin activity by CG7 may be useful for developing a new class of specific IR activators for treatment of Type 1 and Type 2 diabetes.
The optimization of submerged culture conditions and nutritional requirements was studied for the production of exopolysaccharide (EPS) from
Agrocybe cylindracea ASI-9002 using the statistically ...based experimental design in a shake flask culture. Both maximum mycelial biomass and EPS were observed at 25
°C. The optimal initial pH for the production of mycelial biomass and EPS were found to be pH
4.0 and pH
6.0, respectively. Subsequently, optimum concentration of each medium component was determined using the orthogonal matrix method. The optimal combination of the media constituents for mycelial growth was as follows: maltose 80
g/l, Martone A-1 6
g/l, MgSO
4
·
7H
2O 1.4
g/l, and CaCl
2 1.1
g/l; for EPS production: maltose 60
g/l, Martone A-1 6
g/l, MgSO
4
·
7H
2O 0.9
g/l, and CaCl
2 1.1
g/l. Under the optimal culture condition, the maximum EPS concentration achieved in a 5-l stirred-tank bioreactor indicated 3.0
g/l, which is about three times higher than that at the basal medium.
Objectives. To determine the frequency and chemokine receptor-related migratory capacity of CD4+CD25+ regulatory T cells (Tregs) and their association with clinical parameters in patients with SLE. ...Methods. The expression of CD4, CD25, FoxP3 and CCR4 was examined with flow cytometry after staining with fluorescence-conjugated antibodies in 20 patients with SLE, 20 patients with RA and 21 age- and sex-matched healthy controls. For analysis of migration capacity in 24-well chemotaxis chambers, sorted cells were stimulated with ligands of CCR4, CCL17 and CCL22 and analysed with FACScan. Correlations between the number of Tregs and CCR4+ Treg cells and clinical parameters were analysed. Results. The numbers of Tregsbright and CCR4+ Tregsbright were significantly decreased in the patients with SLE compared with healthy controls. The number of Tregsbright was negatively correlated with the levels of anti-dsDNA antibody and the number of CCR4+ Tregsbright had a positive correlation with the levels of C3. Percentage of migrated Tregsbright by CCL17 or CCL22 was significantly decreased in the patients with SLE compared with healthy controls. Conclusions. These results suggest that altered frequency of Tregs and CCR4+ Tregsbright and decreased migratory capacity of Tregs might be involved in the pathogenesis of SLE and indicate that targeting the Tregs can be a new therapeutic strategy in SLE.
Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy ...workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses.
Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany.
Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells.
This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.
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