Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1

Primary microcephaly, Seckel syndrome, and microcephalic osteodysplastic primordial dwarfism type II (MOPD II) are disorders exhibiting marked microcephaly, with small brain sizes reflecting reduced neuron production during fetal life. Although primary microcephaly can be caused by mutations in microcephalin (MCPH1), cells from patients with Seckel syndrome and MOPD II harbor mutations in ataxia telangiectasia and Rad3 related (ATR) or pericentrin (PCNT), leading to disturbed ATR signaling. In this study, we show that a lack of MCPH1 or PCNT results in a loss of Chk1 from centrosomes with subsequently deregulated activation of centrosomal cyclin B–Cdk1

Fermentation of biomass-generated synthesis gas: effects of nitric oxide

The production of renewable fuels, such as ethanol, has been steadily increasing owing to the need for a reduced dependency on fossil fuels. It was demonstrated previously that biomass-generated synthesis gas (biomass-syngas) can be converted to ethanol and acetic acid using a microbial catalyst. The biomass-syngas (primarily CO, CO2, H2, and N2) was generated in a fluidizedbed gasifier and used as a substrate for Clostridium carboxidivorans P7T. Results showed that the cells stopped consuming H2 when exposed to biomass-syngas, thus indicating that there was an inhibition of the hydrogenase enzyme due to some biomass-syngas contaminant. It was hypothesized that nitric oxide (NO) detected in the biomass-syngas could be the possible cause of this inhibition. The specific activity of hydrogenase was monitored with time under varying concentrations of H2 and NO. Results indicated that NO (at gas concentrations above 40 ppm) was a non-competitive inhibitor of hydrogenase activity, although the loss of hydrogenase activity was reversible. In addition, NO also affected the cell growth and increased the amount of ethanol produced. A kinetic model of hydrogenase activity with inhibition by NO was demonstrated with results suggesting there are multiple binding sites of NO on the hydrogenase enzyme. Since other syngas-fermenting organisms utilize the same metabolic pathways, this study estimates that NO<40 ppm can be tolerated by cells in a syngas-fermentation system without compromising the hydrogenase activity, cell growth, and product distribution

MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II

MCPH1, a protein linked to primary microcephaly, directly modulates condensin II to regulate chromosome condensation and shape

CDK5RAP2 functions in centrosome to spindle pole attachment and DNA damage response

Two domains of centrosomal protein CDK5RAP2, CNN1 and CNN2, link centrosomes to mitotic spindle poles. CNN1 lacking centrosomes are unable to recruit pericentriolar matrix components that mediate attachment to spindle poles

ASPM and microcephalin expression in epithelial ovarian cancer correlates with tumour grade and survival

BACKGROUND: The clinico-pathological and molecular heterogeneity of epithelial ovarian cancer (EOC) complicates its early diagnosis and successful treatment. Highly aneuploid tumours and the presence of ascitic fluids are hallmarks of EOC. Two microcephalyassociated proteins, abnormal spindle-like microcephaly-associated protein (ASPM) and microcephalin, are involved in mitosis and DNA damage repair. Their expression is deregulated at the RNA level in EOC. Here, ASPM and microcephalin protein expression in primary cultures established from the ascites of patients with EOC was determined and correlated with clinical data to assess their suitability as biomarkers. METHODS: Five established ovarian cancer cell lines, cells derived from two benign ovarian ascites samples and 40 primary cultures of EOC derived from ovarian ascites samples were analysed by protein slot blotting and/or immunofluorescence to determine ASPM and microcephalin protein levels and their cellular localisation. Results were correlated with clinico-pathological data. RESULTS: A statistically significant correlation was identified for ASPM localisation and tumour grade, with high levels of cytoplasmic ASPM correlating with grade 1 tumours. Conversely, cytoplasmic microcephalin was only identified in high-grade tumours. Furthermore, low levels of nuclear microcephalin correlated with reduced patient survival. CONCLUSION: Our results suggest that ASPM and microcephalin have the potential to be biomarkers in ovarian cance

Biological conversion of carbon monoxide: rich syngas or waste gases to bioethanol

Bioconversion of syngas/waste gas components to produce ethanol appears to be a promising alternative compared to the existing chemical techniques. Recently, several laboratory-scale studies have demonstrated the use of acetogens that have the ability to convert various syngas components (CO, CO2, and H2) to multicarbon compounds, such as acetate, butyrate, butanol, lactate, and ethanol, in which ethanol is often produced as a minor end-product. This bioconversion process has several advantages, such as its high specificity, the fact that it does not require a highly specific H2/CO ratio, and that biocatalysts are less susceptible to metal poisoning. Furthermore, this process occurs under mild temperature and pressure and does not require any costly pre-treatment of the feed gas or costly metal catalysts, making the process superior over the conventional chemical catalytic conversion process. The main challenge faced for commercializing this technology is the poor aqueous solubility of the gaseous substrates (mainly CO and H2). In this paper, a critical review of CO-rich gas fermentation to produce ethanol has been analyzed systematically and published results have been compared. Special emphasis has been given to understand the microbial aspects of the conversion process, by highlighting the role of different micro-organisms used, pathways, and parameters affecting the bioconversion. An analysis of the process fundamentals of various bioreactors used for the biological conversion of CO-rich gases, mainly syngas to ethanol, has been made and reported in this paper. Various challenges faced by the syngas fermentation process for commercialization and future research requirements are also discussed