Identification and characterization of Mini1, a gene regulating rice shoot development

The aerial parts of higher plants are generated from the shoot apical meristem(SAM). In this study, we isolated a small rice(Oryza sativa L.) mutant that showed premature termination of shoot development and was named mini rice 1(mini1). The mutant was first isolated from a japonica cultivar Zhonghua11(ZH11) subjected to ethyl methanesulfonate(EMS)treatment. With bulked segregant analysis(BSA) and map-based cloning method, Mini1 gene was finally fine-mapped to an interval of 48.6 kb on chromosome 9. Sequence analyses revealed a single base substitution from G to A was found in the region, which resulted in an amino acid change from Gly to Asp.The candidate gene Os09g0363900 was predicted to encode a putative adhesion of calyx edges protein ACE(putative HOTHEAD precursor) and genetic complementation experiment confirmed the identity of Mini1. Os09g0363900 contains glucose-methanol-choline(GMC) oxidoreductase and NAD(P)-binding Rossmann-like domain, and exhibits high similarity to Arabidopsis HOTHEAD(HTH). Expression analysis indicated Mini1 was highly expressed in young shoots but lowly in roots and the expression level of most genes involved in auxin biosynthesis and signal transduction were reduced in mutant.We conclude that Mini1 plays an important role in maintaining SAM activity and promoting shoot development in rice.     

Deletion of Dual Specificity Phosphatase 1 Does Not Predispose Mice to Increased Spontaneous Osteoarthritis

Background

Osteoarthritis (OA) is a degenerative joint disease with poorly understood etiology and pathobiology. Mitogen activated protein kinases (MAPKs) including ERK and p38 play important roles in the mediation of downstream pathways involved in cartilage degenerative processes. Dual specificity phosphatase 1 (DUSP1) dephosphorylates the threonine/serine and tyrosine sites on ERK and p38, causing deactivation of downstream signalling. In this study we examined the role of DUSP1 in spontaneous OA development at 21 months of age using a genetically modified mouse model deficient in Dusp1 (DUSP1 knockout mouse).

Results

Utilizing histochemical stains of paraffin embedded knee joint sections in DUSP1 knockout and wild type female and male mice, we showed similar structural progression of cartilage degeneration associated with OA at 21 months of age. A semi-quantitative cartilage degeneration scoring system also demonstrated similar scores in the various aspects of the knee joint articular cartilage in DUSP1 knockout and control mice. Examination of overall articular cartilage thickness in the knee joint demonstrated similar results between DUSP1 knockout and wild type mice. Immunostaining for cartilage neoepitopes DIPEN, TEGE and C1,2C was similar in the cartilage lesion sites and chondrocyte pericellular matrix of both experimental groups. Likewise, immunostaining for phosphoERK and MMP13 showed similar intensity and localization between groups. SOX9 immunostaining demonstrated a decreased number of positive cells in DUSP1 knockout mice, with correspondingly decreased staining intensity. Analysis of animal walking patterns (gait) did not show a discernable difference between groups.

Conclusion

Loss of DUSP1 does not cause changes in cartilage degeneration and gait in a mouse model of spontaneous OA at 21 months of age. Altered staining was observed in SOX9 immunostaining which may prove promising for future studies examining the role of DUSPs in cartilage and OA, as well as models of post-traumatic OA.     

Response of Woodpecker's Head during Pecking Process Simulated by Material Point Method

Prevention of brain injury in woodpeckers under high deceleration during the pecking process has been an intriguing biomechanical problem for a long time. Several studies have provided different explanations, but the function of the hyoid bone, one of the more interesting skeletal features of a woodpecker, still has not been fully explored. This paper studies the relationship between a woodpecker head’s response to impact and the hyoid bone. Based on micro-CT scanning images, the material point method (MPM) is employed to simulate woodpecker’s pecking process. The maximum shear stress in the brainstem (SSS) is adopted as an indicator of brain injury. The motion and deformation of the first cervical vertebra is found to be the main reason of the shear stress of the brain. Our study found that the existence of the hyoid bone reduces the SSS level, enhances the rigidity of the head, and suppresses the oscillation of the endoskeleton after impact. The mechanism is explained by a brief mechanical analysis while the influence of the material properties of the muscle is also discussed.     

Intraovarian Transplantation of Female Germline Stem Cells Rescue Ovarian Function in Chemotherapy-Injured Ovaries

Early menopause and infertility often occur in female cancer patients after chemotherapy (CTx). For these patients, oocyte/embryo cryopreservation or ovarian tissue cryopreservation is the current modality for fertility preservation. However, the above methods are limited in the long-term protection of ovarian function, especially for fertility preservation (very few females with cancer have achieved pregnancy with cryopreserved ovarian tissue or eggs until now). In addition, the above methods are subject to their scope (females with no husband or prepubertal females with no mature oocytes). Thus, many females who suffer from cancers would not adopt the above methods pre- and post-CTx due to their uncertainty, safety and cost-effectiveness. Therefore, millions of women have achieved long-term survival after thorough CTx treatment and have desired to rescue their ovarian function and fertility with economic, durable and reliable methods. Recently, some studies showed that mice with infertility caused by CTx can produce normal offspring through intraovarian injection of exogenous female germline stem cells (FGSCs). Though exogenous FGSC can be derived from mice without immune rejection in the same strain, it is difficult to obtain human female germline stem cells (hFGSCs), and immune rejection could occur between different individuals. In this study, infertility in mice was caused by CTx, and the ability of FGSCs to restore ovarian function or even produce offspring was assessed. We had successfully isolated and purified the FGSCs from adult female mice two weeks after CTx. After infection with GFP-carrying virus, the FGSCs were transplanted into ovaries of mice with infertility caused by CTx. Finally, ovarian function was restored and the recipients produced offspring long-term. These findings showed that mice with CTx possessed FGSCs, restoring ovarian function and avoiding immune rejection from exogenous germline stem cells.     

Prediction of Severe Acute Pancreatitis Using a Decision Tree Model Based on the Revised Atlanta Classification of Acute Pancreatitis

Objective

To develop a model for the early prediction of severe acute pancreatitis based on the revised Atlanta classification of acute pancreatitis.

Methods

Clinical data of 1308 patients with acute pancreatitis (AP) were included in the retrospective study. A total of 603 patients who were admitted to the hospital within 36 hours of the onset of the disease were included at last according to the inclusion criteria. The clinical data were collected within 12 hours after admission. All the patients were classified as having mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) based on the revised Atlanta classification of acute pancreatitis. All the 603 patients were randomly divided into training group (402 cases) and test group (201 cases). Univariate and multiple regression analyses were used to identify the independent risk factors for the development of SAP in the training group. Then the prediction model was constructed using the decision tree method, and this model was applied to the test group to evaluate its validity.

Results

The decision tree model was developed using creatinine, lactate dehydrogenase, and oxygenation index to predict SAP. The diagnostic sensitivity and specificity of SAP in the training group were 80.9% and 90.0%, respectively, and the sensitivity and specificity in the test group were 88.6% and 90.4%, respectively.

Conclusions

The decision tree model based on creatinine, lactate dehydrogenase, and oxygenation index is more likely to predict the occurrence of SAP.     

Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy

Background

Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC.

Methods

Patients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS).

Results

41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib.

Conclusions

The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think the preliminary result here was promising, and further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients.

Trial Registration

ClinicalTrials.gov NCT02430974     

A TagSNP in SIRT1 Gene Confers Susceptibility to Myocardial Infarction in a Chinese Han Population

SIRT1 exerts protective effects against endothelial cells dysfunction, inflammation and atherosclerosis, indicating an important role on myocardial infarction (MI) pathogenesis. Nonetheless, the effects of SIRT1 variants on MI risk remain poorly understood. Here we aimed to investigate the influence of SIRT1 polymorphisms on individual susceptibility to MI. Genotyping of three tagSNPs (rs7069102, rs3818292 and rs4746720) in SIRT1 gene was performed in a Chinese Han population, consisting of 287 MI cases and 654 control subjects. In a logistic regression analysis, we found that G allele of rs7069102 had increased MI risk with odds ratio (OR) of 1.57 [95% confidence interval (CI) = 1.15–2.16, Bonferroni corrected P (P_c) = 0.015] after adjustment for conventional risk factors compared to C allele. Similarly, the combined CG/GG genotypes was associated with the increased MI risk (OR = 1.64, 95% CI = 1.14–2.35, P_c = 0.021) compared to the CC genotype. Further stratified analysis revealed a more significant association with MI risk among younger subjects (≤ 55 years old). Consistent with these results, the haplotype rs7069102G-rs3818292A-rs4746720T containing the rs7069102 G allele was also associated with the increased MI risk (OR = 1.41, 95% CI = 1.09–1.84, P_c = 0.040). However, we did not detect any association of rs3818292 and rs4746720 with MI risk. Our study provides the first evidence that the tagSNP rs7069102 and haplotype rs7069102G-rs3818292A-rs4746720T in SIRT1 gene confer susceptibility to MI in the Chinese Han population.     

A Scheme to Optimize Flow Routing and Polling Switch Selection of Software Defined Networks

This paper aims at minimizing the communication cost for collecting flow information in Software Defined Networks (SDN). Since flow-based information collecting method requires too much communication cost, and switch-based method proposed recently cannot benefit from controlling flow routing, jointly optimize flow routing and polling switch selection is proposed to reduce the communication cost. To this end, joint optimization problem is formulated as an Integer Linear Programming (ILP) model firstly. Since the ILP model is intractable in large size network, we also design an optimal algorithm for the multi-rooted tree topology and an efficient heuristic algorithm for general topology. According to extensive simulations, it is found that our method can save up to 55.76% communication cost compared with the state-of-the-art switch-based scheme.