赖氨酰氧化酶与人类疾病

赖氨酰氧化酶(lysyl oxidases,LOXs)是一种能够催化细胞外基质蛋白(如胶原和弹性蛋白)交叉连接的酶类,这一功能使其在组织的稳定、重塑和伤口愈合中发挥重要作用.随着研究的不断深入,LOXs在细胞增殖、细胞趋化以及肿瘤发生等过程中也彰显出十分关键的作用.研究发现,一些诸如结缔组织病、剥脱综合症、铜代谢障碍性疾病及盆腔器官脱垂和骨疾等疾病的发生与LOXs有很大关系.综述了LOXs的生物合成、结构特点、多功能性以及与人类疾病的关系.     

Progress in plasmodial differentiation improves regularity of oscillating contractions in Physarum polycephalum

Based on the knowledge about subcellular morphogenetic processes in the acellular slime mold Physarum polycephalum, we hypothesized that during differentiation of undifferentiated endoplasm to the highly differentiated complex structure of the contractile apparatus of this organism, the regularity of oscillating contractions must improve. We measured the endogenous contraction automaticity starting from the de novo generation within minutes after sampling small portions of undifferentiated endoplasm. The standard deviation of the normalized period duration of these samples was compared to the respective values of radial contractions of differentiated protoplasmic plasmodial strands. The mean normalized standard deviation in endoplasmic drops was 28.3+/-12.2%. Respective values in protoplasmic strands were 10.0+/-3.7%. The difference between the experimental groups was highly significant (p<0.0001). We interpret the verification of our hypothesis as an indication that the very regular oscillating contractions in fully differentiated stages of Physarum require the complex structure of the sophisticated contractile apparatus, represented by the circular plasmalemma invagination system of protoplasmic strands, while the regularity is lower in stages, where the differentiation is still in progress. We believe that this is due to deficits in coordination capabilities, which need a directional and spatially oriented protoplasmic streaming as a precondition.     

Spectrum of heart diseases in a new cardiac service in Nigeria: An echocardiographic study of 1441 subjects in Abeokuta

Background

The recent determination of the complete nucleotide sequence of several Mycobacterium tuberculosis (MTB) genomes allows the use of comparative genomics as a tool for dissecting the nature and consequence of genetic variability within this species. The multiple alignment of the genomes of clinical strains (CDC1551, F11, Haarlem and C), along with the genomes of laboratory strains (H37Rv and H37Ra), provides new insights on the mechanisms of adaptation of this bacterium to the human host.

Findings

The genetic variation found in six M. tuberculosis strains does not involve significant genomic rearrangements. Most of the variation results from deletion and transposition events preferentially associated with insertion sequences and genes of the PE/PPE family but not with genes implicated in virulence. Using a Perl-based software islandsanalyser, which creates a representation of the genetic variation in the genome, we identified differences in the patterns of distribution and frequency of the polymorphisms across the genome. The identification of genes displaying strain-specific polymorphisms and the extrapolation of the number of strain-specific polymorphisms to an unlimited number of genomes indicates that the different strains contain a limited number of unique polymorphisms.

Conclusion

The comparison of multiple genomes demonstrates that the M. tuberculosis genome is currently undergoing an active process of gene decay, analogous to the adaptation process of obligate bacterial symbionts. This observation opens new perspectives into the evolution and the understanding of the pathogenesis of this bacterium.     

A New Entodiniomorphid Ciliate,Troglocorys cava n. g., n. sp., from the Wild Eastern Chimpanzee (Pan troglodytes schweinfurthii) from Uganda

ABSTRACT. Troglocorys cava n. g., n. sp. is described from the feces of wild eastern chimpanzee, Pan troglodytes schweinfurthii, in Uganda. This new species has a spherical body with a frontal lobe, a long vestibulum, a cytoproct located at the posterior dorsal side of the body, an ovoid macronucleus, a contractile vacuole near the cytoproct, and a large concavity on the left surface of the body. Buccal ciliature is non‐retractable and consists of three ciliary zones: an adoral zone surrounding the vestibular opening, a dorso‐adoral zone extending transversely at the basis of the frontal lobe, and a vestibular zone longitudinally extending in a gently spiral curve to line the surface of the vestibulum. Two non‐retractable somatic ciliary zones comprise arches over the body surface: a short dorsal ciliary arch extending transversely at the basis of the frontal lobe and a wide C‐shaped left ciliary arch in the left concavity. Because of the presence of three ciliary zones in the non‐retractable buccal ciliature, the present genus might be a member of the family Blepharocorythidae, but the large left concavity and the C‐shaped left ciliary arch are unique, such structures have never been described from other blepharocorythids.     

Anti-MJ/NXP-2 autoantibody specificity in a cohort of adult Italian patients with polymyositis/dermatomyositis

Introduction

Increased frequencies of hyperuricemia and gout have been associated with primary hyperparathyroidism, and recent clinical trials of parathyroid hormone (PTH) have reported hyperuricemic adverse events. We evaluated the potential population impact of PTH on serum uric acid (SUA) levels by using a nationally representative sample of United States adults.

Methods

By using data from 8,316 participants aged 18 years and older in the National Health and Nutrition Examination Survey 2003 to 2006, we examined the relation between serum PTH and SUA levels with weighted linear regression. Additionally, we examined the relation with hyperuricemia by using weighted logistic regression.

Results

SUA levels increased with increasing serum PTH concentration. After adjusting for age, sex, dietary factors, glomerular filtration rate (GFR), and other potentially related biomarkers (calcium, phosphorus, alkaline-phosphatase, 25-hydroxyvitamin D), the SUA level differences from the bottom (referent) to top quintiles of serum PTH levels were 0, 8, 13, 14, and 19 ??M (95% CI, 12 to 26; P for trend, < 0.001). These estimates were larger among renally impaired individuals (multivariate SUA difference between the extreme quintiles of PTH, 26 versus 15 ??M among those with GFR ?? 60 versus < 60 ml/min per 1.73 m², respectively) (P for interaction = 0.004). The odds of hyperuricemia by various definitions increased with increasing PTH levels as well (multivariate P values for trend, < 0.05).

Conclusions

These nationally representative data indicate that serum PTH levels are independently associated with serum uric acid levels and the frequency of hyperuricemia at the population level.     

Strain persistence of invasive Candida albicans in chronic hyperplastic candidosis that underwent malignant change

Objectives: The aim of this study was to assess persistence and tissue invasion of Candida albicans strains isolated from a 65 year‐old patient with chronic hyperplastic candidosis (CHC), that subsequently developed into squamous cell carcinoma (SCC). Materials and Methods: C. albicans (n=7) were recovered from the oral cavity of the patient over seven years. Confirmation of CHC and SCC in this patient was achieved by histopathological examination of incisional biopsy tissue. DNA fingerprinting was performed on the seven isolates from the CHC patient together with a further eight isolates from patients with normal oral mucosa (n=2), chronic atrophic candidosis (n=1), SCC (n=1) and CHC (n=4). Genotyping involved the use of inter‐repeat PCR using the eukaryotic repeat primer 1251. Characterisation of the tissue invasive abilities of the isolates was achieved by infecting a commercially available reconstituted human oral epithelium (RHE; SkinEthic, Nice, France). After 24 h. C. albicans tissue invasion was assessed by histopathological examination. Results: DNA fingerprinting demonstrated strain persistence of C. albicans in the CHC patient over a seven year period despite provision of systemic antifungal therapy. The strain of C. albicans isolated from this patient was categorised as a high invader within the RHE compared to other isolates. Conclusions: Candidal strain persistence was evident in a patient with CHC over seven years. This persistence may be due to incomplete eradication from the oral cavity following antifungal therapy or subsequent recolonisation from other body sites or separate exogenous sources. The demonstration of enhanced in vitro tissue invasion by this particular strain may, in part, explain the progression to carcinoma.     

Fast and accurate method for quantitating E. coli host-cell DNA contamination in plasmid DNA preparations

Plasmid DNA is being used successfully as a gene delivery vector in a variety of clinical applications. Similar to other pharmaceutical products for clinical use, the plasmid vectors must meet rigorous purity standards. One important contaminant is the DNA of the host cell used to produce the plasmids. We have developed a new method to accurately quantitate E. coli host-cell DNA in plasmid preparations. This method is based on kinetic PCR using the ABI PRISM 7700 with 23S rDNA as a target. This precise assay is significantly faster and has a lower limit of quantitation than the currently used Southern-based methods.