Using averaged models from 4D ultrasound strain imaging allows to significantly differentiate local wall strains in calcified regions of abdominal aortic aneurysms

Abdominal aortic aneurysms are a degenerative disease of the aorta associated with high mortality. To date, in vivo information to characterize the individual elastic properties of the aneurysm wall in terms of rupture risk is lacking. We have used time-resolved 3D ultrasound strain imaging to calculate spatially resolved in-plane strain distributions characterized by mean and local maximum strains, as well as indices of local variations in strains. Likewise, we here present a method to generate averaged models from multiple segmentations. Strains were then calculated for single segmentations and averaged models. After registration with aneurysm geometries based on CT-A imaging, local strains were divided into two groups with and without calcifications and compared. Geometry comparison from both imaging modalities showed good agreement with a root mean squared error of 1.22 ± 0.15 mm and Hausdorff Distance of 5.45 ± 1.56 mm (mean ± sd, respectively). Using averaged models, circumferential strains in areas with calcifications were 23.2 ± 11.7% (mean ± sd) smaller and significantly distinguishable at the 5% level from areas without calcifications. For single segmentations, this was possible only in 50% of cases. The areas without calcifications showed greater heterogeneity, larger maximum strains, and smaller strain ratios when computed by use of the averaged models. Using these averaged models, reliable conclusions can be made about the local elastic properties of individual aneurysm (and long-term observations of their change), rather than just group comparisons. This is an important prerequisite for clinical application and provides qualitatively new information about the change of an abdominal aortic aneurysm in the course of disease progression compared to the diameter criterion.

     

Heteroplasmy levels of mtDNA1555A>G mutation is positively associated with diverse phenotypes and mutation transmission in a Chinese family

The mtDNA 1555A>G mutation was considered to be one of the most common causes of aminoglycoside-induced and non-syndromic hearing loss. However, this mutation was always found in homoplasmy with high phenotypic heterogeneity. Recently this mutation in heteroplasmy has been reported in several studies. In the present study, we have collected a large Chinese family harboring heteroplasmic mtDNA 1555A>G mutation with diverse clinical phenotypes. To investigate the relationship between the mutation load and the severity of hearing loss under Eastern Asian background, we performed clinical, molecular, genetic and phylogenic analysis. This pedigree was characterized by coexistence of eight subjects with homoplasmic mutation and ten subjects with various degrees of heteroplasmy, and the results suggested that there was a strong correlation between the mutation load and the severity/age-onset of hearing loss (r=0.758, p<0.001). We noticed that the mutation level of offspring was associated with their mothers' in this pedigree, which indicated that maybe exist a regular pattern during the process of the heteroplasmic transmission. In addition, analysis of the complete mtDNA genome of this family revealed that it belonged to Eastern Asian haplogroup B4C1. In addition, a rare homoplasmic mtDNA 9128T>C variant was identified, it located at a strictly conserved site of mtDNA ATP6 gene.     

Antidepressant treatment normalizes white matter volume in patients with major depression

Objective

To investigate white matter volume abnormalities in patients with major depression and the effects of antidepressant treatment on white matter volume.

Method

Magnetic resonance imaging (MRI) was performed on 32 treatment-naïve depressed patients, 17 recovered patients who had received antidepressant treatment and subsequently achieved clinical recovery and 34 matched controls.

Results

Relative to the healthy controls, the treatment-naïve depressed patients showed increased white matter volumes in the left dorsolateral prefrontal cortex (DLPFC) and left putamen and reduced white matter volumes in the left cerebellum posterior lobe and left inferior parietal lobule. For the treatment-naïve patients, the length in months of the current depressive episode was positively correlated with the white matter volumes in both the left DLPFC and left putamen. In the recovered patients, the differences in white matter volume were no longer statistically significant relative to healthy controls. No significant difference was found in the total white matter volume among the three groups.

Conclusions

This study demonstrates that there were alterations in the white matter volumes of depressed patients, which might disrupt the neural circuits that are involved in emotional and cognitive function and thus contribute to the pathophysiology of depression. The finding of the significant correlations between refractoriness and the white matter volumes in the left DLPFC and left putamen combined with the finding that antidepressant treatment normalized the white matter volume of recovered patients, suggests that a quantitative, structural MRI measurement could act as a potential biomarker in depression therapy for individual subjects.     

Biomimetic tubular nanofiber mesh and platelet rich plasma-mediated delivery of BMP-7 for large bone defect regeneration

There is a growing need for successful bone tissue engineering strategies and advanced biomaterials that mimic the structure and function of native tissues carry great promise. Successful bone repair approaches may include an osteoconductive scaffold, osteoinductive growth factors, cells with an osteogenic potential and capacity for graft vascularisation. To increase osteoinductivity of biomaterials, the local combination and delivery of growth factors has been developed. In the present study we investigated the osteogenic effects of calcium phosphate (CaP)-coated nanofiber mesh tube-mediated delivery of BMP-7 from a PRP matrix for the regeneration of critical sized segmental bone defects in a small animal model. Bilateral full-thickness diaphyseal segmental defects were created in twelve male Lewis rats and nanofiber mesh tubes were placed around the defect. Defects received either treatment with a CaP-coated nanofiber mesh tube (n?=?6), an un-coated nanofiber mesh tube (n=6) a CaP-coated nanofiber mesh tube with PRP (n=6) or a CaP-coated nanofiber mesh tube in combination with 5?μg?BMP-7 and PRP (n?=?6). After 12?weeks, bone volume and biomechanical properties were evaluated using radiography, microCT, biomechanical testing and histology. The results demonstrated significantly higher biomechanical properties and bone volume for the BMP group compared to the control groups. These results were supported by the histological evaluations, where BMP group showed the highest rate of bone regeneration within the defect. In conclusion, BMP-7 delivery via PRP enhanced functional bone defect regeneration, and together these data support the use of BMP-7 in the treatment of critical sized defects.     

Identification of new autoantigens for primary biliary cirrhosis using human proteome microarrays

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown etiology and is considered to be an autoimmune disease. Autoantibodies are important tools for accurate diagnosis of PBC. Here, we employed serum profiling analysis using a human proteome microarray composed of about 17,000 full-length unique proteins and identified 23 proteins that correlated with PBC. To validate these results, we fabricated a PBC-focused microarray with 21 of these newly identified candidates and nine additional known PBC antigens. By screening the PBC microarrays with additional cohorts of 191 PBC patients and 321 controls (43 autoimmune hepatitis, 55 hepatitis B virus, 31 hepatitis C virus, 48 rheumatoid arthritis, 45 systematic lupus erythematosus, 49 systemic sclerosis, and 50 healthy), six proteins were confirmed as novel PBC autoantigens with high sensitivities and specificities, including hexokinase-1 (isoforms I and II), Kelch-like protein 7, Kelch-like protein 12, zinc finger and BTB domain-containing protein 2, and eukaryotic translation initiation factor 2C, subunit 1. To facilitate clinical diagnosis, we developed ELISA for Kelch-like protein 12 and zinc finger and BTB domain-containing protein 2 and tested large cohorts (297 PBC and 637 control sera) to confirm the sensitivities and specificities observed in the microarray-based assays. In conclusion, our research showed that a strategy using high content protein microarray combined with a smaller but more focused protein microarray can effectively identify and validate novel PBC-specific autoantigens and has the capacity to be translated to clinical diagnosis by means of an ELISA-based method.     

Salinity-induced changes in protein expression in the halophytic plant Nitraria sphaerocarpa

Salinity is a major abiotic stress that inhibits plant growth and development. Plants have evolved complex adaptive mechanisms that respond to salinity stress. However, an understanding of how plants respond to salinity stress is far from being complete. In particular, how plants survive salinity stress via alterations to their intercellular metabolic networks and defense systems is largely unknown. To delineate the responses of Nitraria sphaerocarpa cell suspensions to salinity, changes in their protein expression patterns were characterized by a comparative proteomic approach. Cells that had been treated with 150 mM NaCl for 1, 3, 5, 7, or 9 days developed several stress-related phenotypes, including those affecting morphology and biochemical activities. Of ~1100 proteins detected in 2-DE gel patterns, 130 proteins showed differences in abundance with more than 1.5-fold when cells were stressed by salinity. All but one of these proteins was identified by MS and database searching. The 129 spots contained 111 different proteins, including those involved in signal transduction, cell rescue/defense, cytoskeleton and cell cycle, protein folding and assembly, which were the most significantly affected. Taken together, our results provide a foundation to understand the mechanism of salinity response.     

Lysosomal membrane permeabilization is involved in curcumin-induced apoptosis of A549 lung carcinoma cells

We previously reported that curcumin inhibited lung cancer A549 cells growth and promoted cell apoptosis in vitro. In this study, we further examined the apoptosis-related parameters, including lysosomal damage and cathepsin activation, in A549 cells exposed to curcumin. We found that curcumin caused lysosomal membrane permeabilization (LMP) and cytosolic relocation of cathepsin B (cath B) and cathepsin D (cath D). However, only Z-FA-fmk (a cath B inhibitor) but not pepstatin A (a cath D inhibitor) inhibited curcumin-induced cell apoptosis, mitochondrial membrane potential loss, and cytochrome c release. The antioxidant N-acetylcysteine and glutathione attenuated LMP, suggesting that lysosomal destabilization was dependent on the elevation of reactive oxygen species and which precedes mitochondrial dysfunction. These findings indicated a novel pathway for curcumin regulation of ROS-lysosomal-mitochondrial pathway and provided the key mechanism of regulation of LMP in cell apoptosis, which may be exploited for cancer treatment.     

杧果蔗糖合成酶MiSS基因的克隆与表达分析

为克隆杧果(Mangifera indica L.)蔗糖合成酶基因序列,预测其编码蛋白特性,阐明其在果实发育过程中的表达规律和作用.本研究采用同源克隆法和RACE技术克隆了1个编码蔗糖合成酶基因的全长cDNA,命名为MiSS,其cDNA全长2110 bp,开放阅读框为1455 bp,编码484个氨基酸,相对分子量为55.3 kD,理论等电点为6.08.系统进化分析显示,MiSS基因编码的氨基酸序列与温州蜜柑(Citrus unshiu)、荔枝(Litchi chinensis)、龙眼(Dimocarpus longan)氨基酸序列一致性为90％～93％.RT-qPCR分析显示,MiSS基因表达量呈现先上升后下降的趋势,且果实发育各时期果皮内MiSS基因表达量均显著高于果肉,综合分析MiSS基因可能与淀粉的合成密切相关.本研究为进一步了解MiSS基因在杧果蔗糖代谢过程中的作用以及从分子角度阐明植物生长调节剂对杧果蔗糖代谢的影响机理奠定了理论和技术基础.     

类叶升麻(毛茛科)自花传粉机制

毛茛科类叶升麻(Actaea asiatica)有2种开花方式, 一种与同属其它植物相同, 花萼片在开花早期脱落, 花药远离柱头; 而另一种较为特殊, 能使该植物进行自花授粉, 即在花开放前, 花萼从花托上脱离, 但萼片并不张开, 部分雄蕊的花丝伸长, 将花药推入萼片和柱头之间, 收缩的花萼片将开裂的花药压在宽大的柱头上, 进而完成自花授粉。套袋实验结果表明, 类叶升麻自发自交具有很高的结籽率, 不具有孤雌生殖和风媒传粉。繁育系统估测分析结果显示, 类叶升麻自交亲和,为兼性自交的繁育系统。