Mitotic catastrophe and endomitosis in tumour cells: an evolutionary key to a molecular solution

Following genotoxic insult, p53 mutated tumour cells undergo mitotic catastrophe. This is characterised by a switch from mitosis to the endocycle. The essential difference between mitosis and the endocycle is that in the latter, DNA synthesis is uncoupled from cell division, which leads to the formation of endopolyploid cells. Recent data suggests that a return from the endocycle into mitosis is also possible. Furthermore, our observations indicate that a particular type of endocycle known as endomitosis may be involved in this return. Here we review the role of endomitosis in the somatic reduction of polyploidy during development and its postulated role in the evolution of meiosis. Finally, we incorporate these evolutionary data to help interpret our most recent observations in the tumour cell system, which indicate a role for endomitosis and meiotic regulators, in particular p39mos in the segregation of genomes (somatic reduction) of these endopolyploid cells.     

An assessment of the DNA barcodes of Indian freshwater fishes

Freshwater fishes in India are poorly known and plagued by many unresolved cryptic species complexes that masks some latent and endemic species. Limitations in traditional taxonomy have resulted in this crypticism. Hence, molecular approaches like DNA barcoding, are needed to diagnose these latent species. We have analyzed 1383 barcode sequences of 175 Indian freshwater fish species available in the databases, of which 172 sequences of 70 species were generated. The congeneric and conspecific genetic divergences were calculated using Kimura's 2 parameter distance model followed by the construction of a Neighbor Joining tree using the MEGA 5.1. DNA barcoding principle at its first hand approach, led to the straightforward identification of 82% of the studied species with 2.9% (S.E = 0.2) divergence between the nearest congeners. However, after validating some cases of synonymy and mislabeled sequences, 5% more species were found to be valid. Sequences submitted to the database under different names were found to represent single species. On the other hand, some sequences of the species like Barilius barna, Barilius bendelisis and Labeo bata were submitted to the database under a single name but were found to represent either some unexplored species or latent species. Overall, 87% of the available Indian freshwater fish barcodes were diagnosed as true species in parity with the existing checklist and can act as reference barcode for the particular taxa. For the remaining 13% (21 species) the correct species name was difficult to assign as they depicted some erroneous identification and cryptic species complex. Thus, these barcodes will need further assay and inclusion of barcodes of more specimens from same and sister species.     

Pollux: platform independent error correction of single and mixed genomes

Background

Second-generation sequencers generate millions of relatively short, but error-prone, reads. These errors make sequence assembly and other downstream projects more challenging. Correcting these errors improves the quality of assemblies and projects which benefit from error-free reads.

Results

We have developed a general-purpose error corrector that corrects errors introduced by Illumina, Ion Torrent, and Roche 454 sequencing technologies and can be applied to single- or mixed-genome data. In addition to correcting substitution errors, we locate and correct insertion, deletion, and homopolymer errors while remaining sensitive to low coverage areas of sequencing projects. Using published data sets, we correct 94% of Illumina MiSeq errors, 88% of Ion Torrent PGM errors, 85% of Roche 454 GS Junior errors. Introduced errors are 20 to 70 times more rare than successfully corrected errors. Furthermore, we show that the quality of assemblies improves when reads are corrected by our software.

Conclusions

Pollux is highly effective at correcting errors across platforms, and is consistently able to perform as well or better than currently available error correction software. Pollux provides general-purpose error correction and may be used in applications with or without assembly.     

突变级数法在生态适宜度评价中的应用——以镇江新区为例

《开发区区域环境影响评价技术导则》（HJ／T2003）已将生态适宜度评价列为区域环境影响评价的主要内容,并明确提出了三级指标集成的框架要求,但并未推荐具体的技术方法。在当前的环评工作实际中,出现了多种生态适宜度的评价技术,如排列成比较技术、层次分析、模糊评价法等,然而这些方法却普遍存在着权重分配过程中的主观性问题。而对于生态适宜度评价这类多指标集成的问题,无论采用何种技术方法,只有减少权重赋值的主观性才能体现评价结论的科学性。鉴于此,推荐了一种新型的生态适宜度评价方法——突变级数法。通过镇江新区环评的具体案例分析,突变级数法表现出在生态适宜度评价方面较好的适用性。更为重要的是,通过对前述3种方法的数理分析对比,突变级数法表现出主营以下两方面的比较优势：首先该法不使用权重,只需按指标间的内在逻辑关系对指标的重要程度进行排序,很大限度地避免了人为制定权重的主观性;同时,作为定性与定量相结合的技术方法,突变级数法不仅可以对各地块是否适合其利用类型做出评价,还可以运用模型计算出各个地块生态适宜度的具体数值,对不同地块的生态适宜性程度进行定量的对比。诚然,应该客观地指出,在按指标的重要程度排序过程、以及评价指标的量化分级过程中,突变级数法仍然不能完全避免人为主观性,这也需要今后继续探索整合其他技术方法。加以进一步完善。     

DNA存储中的编码技术

脱氧核糖核酸(Deoxyribonucleic Acid, DNA)是一种天然的信息存储介质,具有存储密度高、存储时间长、损耗率低等特点。在传统存储方式不能满足信息增长的需求时,DNA数据存储技术逐渐成为研究热点。DNA编码是用尽可能少的碱基序列无错的存储数据信息,包括压缩(尽可能少的占用空间)、纠错(无错存储)和转换(数字信息转为碱基序列)3部分。DNA编码是DNA存储中的关键技术,它的结果直接影响存储性能的优劣和数据读写的完整。本文首先介绍DNA存储的发展历史,然后介绍DNA存储的框架,其中重点介绍DNA编码技术,最后对DNA存储中的编解码技术的未来发展方向进行讨论。     

MDM2 is implicated in high‐glucose‐induced podocyte mitotic catastrophe via Notch1 signalling

Podocyte injury and depletion are essential events involved in the pathogenesis of diabetic nephropathy (DN). As a terminally differentiated cell, podocyte is restricted in ‘post‐mitosis’ state and unable to regenerate. Re‐entering mitotic phase will cause podocyte disastrous death which is defined as mitotic catastrophe (MC). Murine double minute 2 (MDM2), a cell cycle regulator, is widely expressed in renal resident cells including podocytes. Here, we explore whether MDM2 is involved in podocyte MC during hyperglycaemia. We found aberrant mitotic podocytes with multi‐nucleation in DN patients. In vitro, cultured podocytes treated by high glucose (HG) also showed an up‐regulation of mitotic markers and abnormal mitotic status, accompanied by elevated expression of MDM2. HG exposure forced podocytes to enter into S phase and bypass G2/M checkpoint with enhanced expression of Ki67, cyclin B1, Aurora B and p‐H3. Genetic deletion of MDM2 partly reversed HG‐induced mitotic phase re‐entering of podocytes. Moreover, HG‐induced podocyte injury was alleviated by MDM2 knocking down but not by nutlin‐3a, an inhibitor of MDM2‐p53 interaction. Interestingly, knocking down MDM2 or MDM2 overexpression showed inhibition or activation of Notch1 signalling, respectively. In addition, genetic silencing of Notch1 prevented HG‐mediated podocyte MC. In conclusion, high glucose up‐regulates MDM2 expression and leads to podocyte MC. Notch1 signalling is an essential downstream pathway of MDM2 in mediating HG‐induced MC in podocytes.     

CLASP Mediates Microtubule Repair by Restricting Lattice Damage and Regulating Tubulin Incorporation

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A new model for periphyton growth in running waters

A new model for biofilm growth is based on a logistic approach but accounts for detachment of the biofilm by the running water and the existence of a threshold point for growth. Above a critical current velocity, development of periphyton is not stable. A stability analysis shows the existence of a fold catastrophe in the model and the amplification of water velocity fluctuations by the algal biomass.     

Bifurcations in haploid and diploid sequence space models

 Deterministic models of mutation and selection in the space of (binary) nucleotide-type sequences have been investigated for haploid populations during the past 25 years, and, recently, for diploid populations as well. These models, in particular their ‘error thresholds’, have mainly been analyzed by numerical methods and perturbation techniques. We consider them here by means of bifurcation theory, which improves our understanding of both equilibrium and dynamical properties. In a caricature obtained from the original model by neglecting back mutation to the favourable allele, the familiar error threshold of the haploid two-class model turns out to be a simple transcritical bifurcation, whereas its diploid counterpart exhibits an additional saddle node. This corresponds to a second error threshold. Three-class models with neutral spaces of unequal size introduce further features. Such are a global bifurcation in haploid populations, and simple examples of Hopf bifurcations (as predicted by Akin’s theorem) in the diploid case. Received 13 June 1995; received in revised form 26 July 1996     

Paclitaxel-induced aberrant mitosis and mitotic slippage efficiently lead to proliferative death irrespective of canonical apoptosis and p53

Spindle poisons elicit various cellular responses following metaphase arrest, but how they relate to long-term clonogenicity has remained unclear. We prepared several HeLa lines in which the canonical apoptosis pathway was attenuated, and compared their acute responses to paclitaxel, as well as long-term fate, with the parental line. Three-nanomolar paclitaxel induced brief metaphase arrest (<5 h) often followed by aberrant mitosis, and about 90% of the cells of each line had lost their clonogenicity after 48 h of the treatment. A combination of the same concentration of paclitaxel with the kinesin-5 inhibitor, S-trityl-L-cysteine (STLC), at 1 µM led to much longer arrest (～20 h) and predominance of subsequent line-specific responses: mitochondrial outer membrane permeabilization (MOMP) in the apoptosis-prone line, or mitotic slippage without obvious MOMP in the apoptosis-reluctant lines. In spite of this, combination with STLC did not lead to a marked difference in clonogenicity between the apoptosis-prone and -reluctant lines, and intriguingly resulted in slightly better clonogenicity than that of cells treated with 3 nM paclitaxel alone. This indicates that changes in the short-term response within 3 possible scenarios — acute MOMP, mitotic slippage or aberrant mitosis ― has only a weak impact on clonogenicity. Our results suggest that once cells have committed to slippage or aberrant mitosis they eventually undergo proliferative death irrespective of canonical apoptosis or p53 function. Consistent with this, cells with irregular DNA contents originating from mitotic slippage or aberrant mitosis were mostly eliminated from the population within several rounds of division after the drug treatment.