MYH9: structure,functions and role of non-muscle myosin ⅡA in human disease

MYH9-related diseases (MYH9-RD) are a group of autosomal dominant diseases caused by mutations in the MYH9 gene, which are featured by thrombocytopenia, giant platelets and granulocyte cytoplasmic inclusion bodies. MYH9-RD patients generally suffer from bleeding syndromes, progressive kidney disease, deafness, or cataracts. Here, we reported on a case of MYH9-RD. A novel heterozygous mutation of MYH9 (c.2344-2345delGTinsTA, p.T782Y) was discovered by targeted sequencing technology. Immunofluorescence analysis of neutrophils confirmed abnormal aggregation of MYH9 protein. The results of this study should expand the MYH9 gene mutation spectrum and provide reference for subsequent researchers and genetic counseling.     

Which Urban Migrants Default from Tuberculosis Treatment in Shanghai,China?

Background

Migration is a major challenge to tuberculosis (TB) control worldwide. TB treatment requires multiple drugs for at least six months. Some TB patients default before completing their treatment regimen, which can lead to ongoing infectiousness and drug resistance.

Methods

We conducted a retrospective analysis of 29,943 active TB cases among urban migrants that were reported between 2000 to 2008 in Shanghai, China. We used logistic regression models to identify factors independently associated with treatment defaults in TB patients among urban migrants during 2005-2008.

Results

Fifty-two percent of the total TB patients reported in Shanghai during the study period were among urban migrants. Three factors increased the odds of a treatment default: case management using self-administered therapy (OR, 5.84, 95% CI, 3.14-10.86, p<0.0005), being a retreatment case (OR, 1.47, 95% CI, 1.25-1.71, p<0.0005), and age >60 years old (OR, 1.33, 95% CI, 1.05-1.67, p=0.017). The presence of a cavity in the initial chest radiograph decreased the odds for a treatment default (OR, 0.87, 95% CI, 0.77-0.97, p=0.015), as did migration from central China (OR, 0.85, 95% CI, 0.73-0.99, p=0.042), case management by family members (OR, 0.73, 95% CI 0.66-0.81, p<0.0005), and the combination of case detection by a required physical exam and case management by health care staff (OR, 0.64, 95% CI, 0.45-0.93, p=0.019).

Conclusion

Among TB patients who were urban migrants in Shanghai, case management using self-administered therapy was the strongest modifiable risk factor that was independently associated with treatment defaults. Interventions that target retreated TB cases could also reduce treatment defaults among urban migrants. Health departments should develop effective measures to prevent treatment defaults among urban migrants, to ensure completion of therapy among urban migrants who move between cities and provinces, and to improve reporting of treatment outcomes.     

A Homogeneous,High-Throughput Assay for Phosphatidylinositol 5-Phosphate 4-Kinase with a Novel,Rapid Substrate Preparation

Phosphoinositide kinases regulate diverse cellular functions and are important targets for therapeutic development for diseases, such as diabetes and cancer. Preparation of the lipid substrate is crucial for the development of a robust and miniaturizable lipid kinase assay. Enzymatic assays for phosphoinositide kinases often use lipid substrates prepared from lyophilized lipid preparations by sonication, which result in variability in the liposome size from preparation to preparation. Herein, we report a homogeneous 1536-well luciferase-coupled bioluminescence assay for PI5P4Kα. The substrate preparation is novel and allows the rapid production of a DMSO-containing substrate solution without the need for lengthy liposome preparation protocols, thus enabling the scale-up of this traditionally difficult type of assay. The Z’-factor value was greater than 0.7 for the PI5P4Kα assay, indicating its suitability for high-throughput screening applications. Tyrphostin AG-82 had been identified as an inhibitor of PI5P4Kα by assessing the degree of phospho transfer of γ-³²P-ATP to PI5P; its inhibitory activity against PI5P4Kα was confirmed in the present miniaturized assay. From a pilot screen of a library of bioactive compounds, another tyrphostin, I-OMe tyrphostin AG-538 (I-OMe-AG-538), was identified as an ATP-competitive inhibitor of PI5P4Kα with an IC₅₀ of 1 µM, affirming the suitability of the assay for inhibitor discovery campaigns. This homogeneous assay may apply to other lipid kinases and should help in the identification of leads for this class of enzymes by enabling high-throughput screening efforts.     

豚鼠冰水游泳应激后血浆、肾上腺髓质和脑内组织的亮—脑啡肽含量变化

豚鼠冰水游泳应激3min后,用放射免疫法测定血浆、肾上腺髓质和脑内三个脑区组织的亮—脑啡肽(Leu-enkephalin,LEK,)含量和血浆的血管紧张肽Ⅱ(Angiotensin Ⅱ,ATⅡ)浓度变化。结果表明:在冰水中游泳应激组豚鼠的血浆、肾上腺髓质、下丘脑和纹状体组织的LEK含量和血浆的ATⅡ浓度,均较对照组豚鼠明显升高(P值均<0.01)。提示:豚鼠在冰水中紧张、剧烈游泳后,可能激活了中枢神经和周围组织内的脑啡肽能神经元和血管紧张肽原酶—血管紧张肽Ⅱ系统,从而促进LEK和ATⅡ的释放增加。     

Roles of phospholipase D in phorbol myristate acetate‐stimulated neutrophil respiratory burst

The phorbol myristate acetate (PMA) stimulated nutrophil respiratory burst has been considered to simply involve the activation of protein kinase C (PKC). However, the PLD activity was also increased by 10‐fold in human neutrophils stimulated with 100 nM PMA. Unexpectedly, U73122, an inhibitor of phospholipase C, was found to significantly inhibit PMA‐stimulated respiratory burst in human neutrophils. U73122 at the concentrations, which were sufficient to inhibit the respiratory burst completely, caused partial inhibition of the PLD activity but no inhibition on PKC translocation and activation, suggesting that PLD activity is also required in PMA‐stimulated respiratory burst. Using 1‐butanol, a PLD substrate, to block phosphatidic acid (PA) generation, the PMA‐stimulated neutrophil respiratory burst was also partially inhibited, further indicating that PLD activation, possibly its hydrolytic product PA and diacylglycerol (DAG), is involved in PMA‐stimulated respiratory burst. Since GF109203X, an inhibitor of PKC that could completely inhibit the respiratory burst in PMA‐stimulated neutrophils, also caused certain suppression of PLD activation, it may suggest that PLD activation in PMA‐stimulated neutrophils might be, to some extent, PKC dependent. To further study whether PLD contributes to the PMA stimulated respiratory burst through itself or its hydrolytic product, 1,2‐dioctanoyl‐sn‐glycerol, an analogue of DAG , was used to prime cells at low concentration, and it reversed the inhibition of PMA‐stimulated respiratory burst by U73122. The results indicate that U73122 may act as an inhibitor of PLD, and PLD activation is required in PMA‐stimulated respiratory burst.     

Oxygen‐Deficient Blue TiO2 for Ultrastable and Fast Lithium Storage

Developing a titanium dioxide (TiO₂)‐based anode with superior high‐rate capability and long‐term cycling stability is important for efficient energy storage. Herein, a simple one‐step approach for fabricating blue TiO₂ nanoparticles with oxygen vacancies is reported. Oxygen vacancies can enlarge lattice spaces, lower charge transfer resistance, and provide more active sites in TiO₂ lattices. As a result, this blue TiO₂ electrode exhibits a highly reversible capacity of 50 mAh g^?1 at 100 C (16 800 mA g^?1) even after 10 000 cycles, which is attributable to the combination of surface capacitive process and remarkable diffusion‐controlled insertion revealed by the kinetic analysis. The strategy of employing oxygen‐deficient nanoparticles may be extended to the design of other robust semiconductor materials as electrodes for energy storage.     

Research progress on the immune mechanism of the silkworm Bombyx mori

The silkworm Bombyx mori L., representing an important economic insect and one of the best models for studying insect immunity, possesses an efficient and sophisticated innate immune system against invasive microorganisms. The innate immune system basically includes humoural immunity and cellular immunity. The humoural immunity, which functions via molecules including humoural factors, lysozymes, phenoloxidase, hemolin, lectins and, in particular, antimicrobial peptides, plays a central role in eliminating the invading pathogens. The cellular immunity is primarily carried out and mediated by plasmatocytes and granular cells of haemocytes in the haemolymph, usually followed by melanization. Additionally, apoptosis, a primary viral defence for insects lacking adaptive immunity, comprises an important part of the silkworm immune system. Currently, there is still the lack of a comprehensive and systematic understanding of the molecular mechanisms of silkworm immunity. We review the latest research progress on silkworm immune mechanisms, including phenoloxidase‐dependent melanization and apoptosis, which is conducive to improving our understanding of the silkworm immune mechanism, clarifying the relationship of various immune mechanisms, and also providing a theoretical basis and reference for the future research of insect immunity.