Differential Immune Responses and Protective Effects in Avirulent Mycobacterial Strains Vaccinated BALB/c Mice

Screening live mycobacterial vaccine candidates is the important strategy to develop new vaccines against adult tuberculosis (TB). In this study, the immunogenicity and protective efficacy of several avirulent mycobacterial strains including Mycobacterium smegmatis, M. vaccae, M. terrae, M. phlei, M. trivial, and M. tuberculosis H37Ra were compared with M. bovis BCG in BALB/c mice. Our results demonstrated that differential immune responses were induced in different mycobacterial species vaccinated mice. As BCG-vaccinated mice did, M. terrae immunization resulted in Th1-type responses in the lung, as well as splenocytes secreting IFN-γ against a highly conserved mycobacterial antigen Ag85A. M. smegmatis also induced the same splenocytes secreting IFN-γ as BCG and M. terrae did. In addition, M. terrae and M. smegmatis-immunized mice predominantly increased expression of IL-10 and TGF-β in the lung. Most importantly, mice vaccinated with H37Ra and M. vaccae could provide the same protection in the lung against virulent M. tuberculosis challenge as BCG. The result may have important implications in developing adult TB vaccine.     

工业微生物酸胁迫的耐受机制及改造途径

工业微生物在发酵生产过程中会面对发酵环境和自身产生的各类酸性物质,而这些酸性物质会影响工业微生物的生长和代谢,即产生酸胁迫。微生物通过调控胞内质子浓度、保护和修复生物大分子、改变细胞膜组分以及整体水平调控等耐受机制来应对酸胁迫。结合酸胁迫的各种耐受机制,利用自然筛选和人工改造的方法提高工业微生物的抗酸胁迫能力,为构建出更能适应工业生产条件的菌株提供理论依据。     

莴苣与高羊茅对蓝花楹花水浸液化感作用的响应

为探明蓝花楹是否存在对其它植物产生化感作用的相关物质,以生长在四川温江地区的蓝花楹完整单花为供体材料、莴苣与高羊茅为受体材料、清水处理为对照(CK),采用培养皿滤纸法进行种子萌发以及生物测定法培养幼苗,研究浓度为0.001、0.025、0.050 g·m L-1的蓝花楹花水浸液对莴苣与高羊茅的种子萌发幼苗生长的化感作用。结果表明:莴苣与高羊茅的种子萌发均受到该水浸液的抑制作用,在萌发指数上表现较明显即综合化感效应(SE2)分别表现为-0.13、-0.27;莴苣的苗高受到促进作用而根长和根冠比却受到抑制作用,其苗高SE3=0.13、根长SE4=-0.36、根冠比SE5=-0.16;高羊茅的根冠比受到促进作用而苗高和根长却受到抑制作用,其SE3=-0.12、SE4=-0.08、SE5=0.16;莴苣叶片丙二醛含量和根系活力值均受到抑制作用,其丙二醛含量的SE6=-0.25和根系活力SE7=-0.44,高羊茅的响应则相反,分别表现为SE6=0.04和SE7=0.34。当水浸液浓度为0.025 g·m L-1时,多处出现RI极值或某种趋势的拐点,特别是受体植物的叶片丙二醛含量和根系活力值的变化。研究结果表明蓝花楹花水浸液中存在化感物质,莴苣与高羊茅对其均有不同响应,这为蓝花楹在植物景观配置及养护上提供了理论依据。     

Solution structure of a bacterial immunoglobulin‐like domain of the outer membrane protein (LigB) from Leptospira

Leptospiral immunoglobulin‐like (Lig) proteins are surface proteins expressed in pathogenic strains of Leptospira. LigB, an outer membrane protein containing tandem repeats of bacterial Ig‐like (Big) domains and a no‐repeat tail, has been identified as a virulence factor involved in adhesion of pathogenic Leptospira interrogans to host cells. A Big domain of LigB, LigBCen2R, was reported previously to bind the GBD domain of fibronectin, suggesting its important role in leptospiral infections. In this study, we determined the solution structure of LigBCen2R by nuclear magnetic resonance (NMR) spectroscopy. LigBCen2R adopts a canonical immunoglobulin‐like fold which is comprised of a beta‐sandwich of ten strands in three sheets. We indicated that LigBCen2R is able to bind to Ca²⁺ with a high affinity by isothermal titration calorimetry assay. NMR perturbation experiment identified a number of residues responsible for Ca²⁺ binding. Structural comparison of it with other Big domains demonstrates that they share a similar fold pattern, but vary in some structural characters. Since Lig proteins play a vital role in the infection to host cells, our study will contribute a structural basis to understand the interactions between Leptospira and host cells. Proteins 2015; 83:195–200. © 2014 Wiley Periodicals, Inc.     

基于Landsat 8影像的不同燃烧指数在农田秸秆焚烧区域识别中的应用

农田秸秆焚烧造成秸秆资源的巨大浪费和大气环境的污染,利用热红外波段识别火点的方法可以实时、快速地获取焚烧情况,但是不能提供秸秆焚烧的面积、范围等详细的空间分布情况,也不能确定焚烧的严重程度.利用已燃烧与未燃烧区域的光谱差异选择某些波段构建燃烧指数的方法在森林火灾研究中得到了广泛应用,但是这些指数在农田秸秆焚烧中的潜在应用没有被研究.本文基于松嫩平原地区的两景Landsat 8卫星影像,采用归一化燃烧率（NBR）、引入热红外波段的归一化燃烧率（NBRT）、燃烧面积指数（BAI）3种燃烧指数对农田秸秆焚烧和未焚烧区域进行提取,并与秸秆覆盖度进行相关分析.结果表明：NBR、NBRT和BAI指数对焚烧和未焚烧区域的分类精度分别为91.9%、92.3%、87.8%,NBR、NBRT与覆盖度呈线性相关,R²分别为0.73、0.64,BAI与覆盖度呈幂指数相关关系,R²为0.68.燃烧指数方法可以在农田秸秆焚烧中得到很好的应用,可定量评估秸秆燃烧程度,为大气环境评价提供技术与数据支持.     

嵌合分子(DHT-PROTAC)在前列腺癌研究中的进展

前列腺癌多发于老年男性,已成为老年男性常见肿瘤之一。内分泌治疗目前是晚期前列腺癌主要治疗方法,但仍避免不了前列腺癌最终进展成激素非依赖性前列腺癌,导致内分泌治疗的失败。当前,对前列腺癌细胞株的AR表达的研究,主要集中在DNA水平及mRNA水平,而对AR蛋白翻译后调控的研究较少。近些年来,嵌合分子(DHT-PROTAC)是基于蛋白水平,调控AR蛋白的表达,成为研究前列腺癌转归新的热点。DHT-PROTAC是一种新型人工合成的异型双功能小分子;这种小分子是DHT与泛素连接酶E3识别基团的嵌合体,它不仅能与AR结合,而且能在结合后,诱导AR的泛素化,从而通过泛素-蛋白酶途径降解AR;本文介绍了嵌合分子的作用原理,回顾了近些年前列腺癌的治疗进展,分析了嵌合分子将来在前列腺癌治疗中的应用前景。     

Beneficial effects of inhaled NO on apoptotic pneumocytes in pulmonary thromboembolism model

Background

Lung ischemia–reperfusion injury (LIRI) may occur in the region of the affected lung after reperfusion therapy. Inhaled NO may be useful in treating acute and chronic pulmonary thromboembolism (PTE) due to the biological effect property of NO.

Methods

A PTE canine model was established through selectively embolizing blood clots to an intended right lower lobar pulmonary artery. PaO2/FiO2, the mPAP and PVR were investigated at the time points of 2, 4, 6 hours after inhaled NO. Masson’s trichrome stain, apoptotic pneumocytes and lung sample ultrastructure were also investigated among different groups.

Results

The PaO2/FiO2 in the Inhaled NO group increased significantly when compared with the Reperfusion group at time points of 4 and 6 hours after reperfusion, mPAP decreased significantly at point of 2 hours and the PVR decreased significantly at point of 6 hours after reperfusion. The amounts of apoptotic type II pneumocytes in the lower lobar lung have negative correlation trend with the arterial blood PaO2/FiO2 in Reperfusion group and Inhaled NO group. Inhaled nitric oxide given at 20 ppm for 6 hours can significantly alleviate the LIRI in the model.

Conclusions

Dramatic physiological improvements are seen during the therapeutic use of inhaled NO in pulmonary thromboembolism canine model. Inhaled NO may be useful in treating LIRI in acute or chronic PTE by alleviating apoptotic type II pneumocytes. This potential application warrants further investigation.

     

An Improved Model for Nucleation-Limited Ice Formation in Living Cells during Freezing

Ice formation in living cells is a lethal event during freezing and its characterization is important to the development of optimal protocols for not only cryopreservation but also cryotherapy applications. Although the model for probability of ice formation (PIF) in cells developed by Toner et al. has been widely used to predict nucleation-limited intracellular ice formation (IIF), our data of freezing Hela cells suggest that this model could give misleading prediction of PIF when the maximum PIF in cells during freezing is less than 1 (PIF ranges from 0 to 1). We introduce a new model to overcome this problem by incorporating a critical cell volume to modify the Toner''s original model. We further reveal that this critical cell volume is dependent on the mechanisms of ice nucleation in cells during freezing, i.e., surface-catalyzed nucleation (SCN) and volume-catalyzed nucleation (VCN). Taken together, the improved PIF model may be valuable for better understanding of the mechanisms of ice nucleation in cells during freezing and more accurate prediction of PIF for cryopreservation and cryotherapy applications.     

Factors Predicting Malignancy in Patients with Polymyositis and Dermatomyostis: A Systematic Review and Meta-Analysis

Objective

To define potential factors that could predict concomitant neoplastic diseases in patients diagnosed with PM/DM, which could inform screening decisions.

Methods

Two researchers independently reviewed articles from Pubmed (MEDLINE), EMBASE, Cochrane Plus Library and ISI Web of Knowledge with no restrictions on study design or language. Given that some of the studies combined PM and DM patients as research subjects while others included only DM patients, data were subjected to meta-analyses for all combined PM/DM studies and studies that included only DM patients to obtain informative results.

Results

For PM/DM patients, the following factors are all associated with an increased risk of malignancy: older age, age greater than 45, male sex, dysphagia, cutaneous necrosis, cutaneous vasculitis, rapid onset of myostis (<4 weeks), elevated CK, higher ESR, higher CRP levels. Several factors were associated with lower-than-average risk, including the presence of ILD, arthritis/arthralgia, Raynaud''s syndrome, or anti-Jo-1 antibody. For DM patients, results indicated an increased risk of malignancy with older age, male sex, the presence of cutaneous necrosis, elevated ESR (>35 mm/hr), higher CRP levels, or anti-p155 antibody. In addition, the presence of anti-ENA antibodies seem to be related to reduced risk of malignancy.

Conclusion

Awareness and implementation of early-stage cancer screening in PM/DM patients who have these identified factors – such as being older than 45, male sex, cutaneous necrosis, cutaneous vasculitis – are of crucial importance from public health and clinical perspectives and provide insight into the etiopathogenesis of CAM.