Metarhizium robertsii Produces an Extracellular Invertase (MrINV) That Plays a Pivotal Role in Rhizospheric Interactions and Root Colonization

As well as killing pest insects, the rhizosphere competent insect-pathogenic fungus Metarhizium robertsii also boosts plant growth by providing nitrogenous nutrients and increasing resistance to plant pathogens. Plant roots secrete abundant nutrients but little is known about their utilization by Metarhizium spp. and the mechanistic basis of Metarhizium-plant associations. We report here that M. robertsii produces an extracellular invertase (MrInv) on plant roots. Deletion of MrInv (⊿MrInv) reduced M. robertsii growth on sucrose and rhizospheric exudates but increased colonization of Panicum virgatum and Arabidopsis thaliana roots. This could be accounted for by a reduction in carbon catabolite repression in ⊿MrInv increasing production of plant cell wall-degrading depolymerases. A non-rhizosphere competent scarab beetle specialist Metarhizium majus lacks invertase which suggests that rhizospheric competence may be related to the sugar metabolism of different Metarhizium species.     

帕金森病的临床治疗概况

帕金森病(Parkinson's disease, PD),在医学上称为"原发性震颤麻痹",又称"震颤麻痹",是一种中枢神经系统变性疾病,主要是因位于中脑部位"黑质"中的多巴胺(DA)能神经元病理性改变后,多巴胺的合成减少,对与其功能相互拮抗的乙酰胆碱的抑制功能降低,则乙酰胆碱的兴奋作用相对增强。两者失衡的结果便出现了"震颤麻痹"。本综述先从PD发病机制方向总结归纳目前临床常用的西医药物(包括左旋多巴、DA降解酶抑制剂、DA受体激动剂、抗胆碱能药物)、基因治疗靶点、手术治疗(脑深部电刺激术)及物理疗法,又从中医角度整体介绍了目前中医中药治疗以及针灸治疗等。因PD对患者的日常生活及身心健康造成了严重影响,我们希望通过本综述为PD综合治疗提供更广阔的临床思路及更好的方案。     

MiR-423-5p inhibition alleviates cardiomyocyte apoptosis and mitochondrial dysfunction caused by hypoxia/reoxygenation through activation of the wnt/β-catenin signaling pathway via targeting MYBL2

MicroRNA (miR) plays an integral role in cardiovascular diseases. M-iR-423-5p is aberrantly expressed in patients with myocardial infarction and heart failure. The aim of the present study was to study the roles and mechanisms of miR-423-5p in hypoxia/reoxygenation (H/R) mediated cardiomyocytes injury. H9C2 cells were transfected with negative control, miR-423-5p mimic, and inhibitor for 48 hr, followed by exposed to H/R condition. Cell apoptosis rate, caspase 3/7 activities, Bax and cleaved-caspase 3 (c-caspase 3) protein levels were assayed by flow cytometry, Caspase-Glo 3/7 Assay kit, western blot analysis, respectively. Furthermore, the mitochondrial membrane potential, adenosine triphosphate (ATP) content, reactive oxygen species (ROS) production, and Drp1 expression were also investigated. Furthermore, the dual-luciferase reporter assay was used to evaluate the relationship between miR-423-5p and Myb-related protein B (MYBL2). The roles of miR-423-5p in wnt/β-catenin were assessed by western blot analysis. The results revealed that H/R triggered miR-423-5p expression. Overexpression of miR-423-5p promoted cardiomyocyte apoptosis, enhanced the activities of caspase 3/7, upregulated the expression of Bax and c-caspase 3. miR-423-5p upregulation caused the loss of mitochondrial membrane potential and the reduction of ATP content, the augment of ROS production and Drp1 expression. However, the opposite trends were observed upon suppression of miR-423-5p. In addition, miR-423-5p could target the 3′ untranslated region of MYBL2. miR-423-5p depletion led to the activation of the wnt/β-catenin signaling pathway via targeting MYBL2. Knockdown of MYBL2 was obviously reversed the roles of miR-423-5p in apoptosis and mitochondrial dysfunction. Taken together, miR-423-5p suppression reduced H/R-induced cardiomyocytes injury through activation of the wnt/β-catenin signaling pathway via targeting MYBL2 in cardiomyocytes.     

RNA sequencing reveals two major classes of gene expression levels in metazoan cells

The expression level of a gene is often used as a proxy for determining whether the protein or RNA product is functional in a cell or tissue. Therefore, it is of fundamental importance to understand the global distribution of gene expression levels, and to be able to interpret it mechanistically and functionally. Here we use RNA sequencing (RNA‐seq) of mouse Th2 cells, coupled with a range of other techniques, to show that all genes can be separated, based on their expression abundance, into two distinct groups: one group comprised of lowly expressed and putatively non‐functional mRNAs, and the other of highly expressed mRNAs with active chromatin marks at their promoters. These observations are confirmed in many other microarray and RNA‐seq data sets of metazoan cell types.     

Toxoplasma gondii α-amylase deletion mutant is a promising vaccine against acute and chronic toxoplasmosis

Individuals with inhibited immunity may develop lethal toxoplasmosis; thus, a safe and effective vaccine is urged to be developed. Toxoplasma gondii (T. gondii) α-amylase (α-AMY) is one of the enzymes responsible for starch digestion. In the present study, we first generated a ME49Δα-amy mutant and discovered that loss of α-AMY robustly grew in vitro but contributed to significant virulence attenuation in vivo. Therefore, we established a mouse model to explore the protective immunity of Δα-amy mutant against acute and chronic toxoplasmosis. The results indicated that the survival rates of short-term or long-term immunized mice re-infected with the tachyzoites of multiple T. gondii strains were nearly 100%. ME49Δα-amy not only could provide protective immunity against tachyzoites infection but also could resist the infection of tissue cysts. Furthermore, we detected that ME49Δα-amy vaccination could effectively eliminate the proliferation of parasites in mice and prevent the formation of cysts. The significant increases of Th1-type cytokines, Th2-type cytokines and specific total IgG and IgG subclasses (IgG2a and IgG1) confirmed efficiency of a combination of cellular and humoral immunity against infection. In conclusion, ME49Δα-amy attenuated strain can produce strong immune responses to provide efficient protection against toxoplasmosis, which signifies that ME49Δα-amy mutant may be a potential vaccine candidate.     

Why Has the Number of Scientific Retractions Increased?

Background

The number of retracted scientific publications has risen sharply, but it is unclear whether this reflects an increase in publication of flawed articles or an increase in the rate at which flawed articles are withdrawn.

Methods and Findings

We examined the interval between publication and retraction for 2,047 retracted articles indexed in PubMed. Time-to-retraction (from publication of article to publication of retraction) averaged 32.91 months. Among 714 retracted articles published in or before 2002, retraction required 49.82 months; among 1,333 retracted articles published after 2002, retraction required 23.82 months (p<0.0001). This suggests that journals are retracting papers more quickly than in the past, although recent articles requiring retraction may not have been recognized yet. To test the hypothesis that time-to-retraction is shorter for articles that receive careful scrutiny, time-to-retraction was correlated with journal impact factor (IF). Time-to-retraction was significantly shorter for high-IF journals, but only ∼1% of the variance in time-to-retraction was explained by increased scrutiny. The first article retracted for plagiarism was published in 1979 and the first for duplicate publication in 1990, showing that articles are now retracted for reasons not cited in the past. The proportional impact of authors with multiple retractions was greater in 1972–1992 than in the current era (p<0.001). From 1972–1992, 46.0% of retracted papers were written by authors with a single retraction; from 1993 to 2012, 63.1% of retracted papers were written by single-retraction authors (p<0.001).

Conclusions

The increase in retracted articles appears to reflect changes in the behavior of both authors and institutions. Lower barriers to publication of flawed articles are seen in the increase in number and proportion of retractions by authors with a single retraction. Lower barriers to retraction are apparent in an increase in retraction for “new” offenses such as plagiarism and a decrease in the time-to-retraction of flawed work.     

MicroRNA Profiling in Prostate Cancer - The Diagnostic Potential of Urinary miR-205 and miR-214

Prostate cancer (PCa) is the most common type of cancer in men in the United States, which disproportionately affects African American descents. While metastasis is the most common cause of death among PCa patients, no specific markers have been assigned to severity and ethnic biasness of the disease. MicroRNAs represent a promising new class of biomarkers owing to their inherent stability and resilience. In the present study, we investigated potential miRNAs that can be used as biomarkers and/or therapeutic targets and can provide insight into the severity and ethnic biasness of PCa. PCR array was performed in FFPE PCa tissues (5 Caucasian American and 5 African American) and selected differentially expressed miRNAs were validated by qRT-PCR, in 40 (15 CA and 25 AA) paired PCa and adjacent normal tissues. Significantly deregulated miRNAs were also analyzed in urine samples to explore their potential as non-invasive biomarker for PCa. Out of 8 miRNAs selected for validation from PCR array data, miR-205 (p<0.0001), mir-214 (p<0.0001), miR-221(p<0.001) and miR-99b (p<0.0001) were significantly downregulated in PCa tissues. ROC curve shows that all four miRNAs successfully discriminated between PCa and adjacent normal tissues. MiR-99b showed significant down regulation (p<0.01) in AA PCa tissues as compared to CA PCa tissues and might be related to the aggressiveness associated with AA population. In urine, miR-205 (p<0.05) and miR-214 (p<0.05) were significantly downregulated in PCa patients and can discriminate PCa patients from healthy individuals with 89% sensitivity and 80% specificity. In conclusion, present study showed that miR-205 and miR-214 are downregulated in PCa and may serve as potential non-invasive molecular biomarker for PCa.     

Tortuosity of the superficial femoral artery and its influence on blood flow patterns and risk of atherosclerosis

Biomechanics and Modeling in Mechanobiology - The superficial femoral artery (SFA) is a typical atherosclerosis-prone site. We aimed to explore whether the tortuosity of the SFA associates with the...