Among the 3 billion base pairs of the human genome, there are approximately 30,000-40,000 protein-coding genes, but the function of at least half of them remains unknown. A new tool - short interfering RNAs (siRNAs) - has now been developed for systematically deciphering the functions and interactions of these thousands of genes. siRNAs are an intermediate of RNA interference, the process by which double-stranded RNA silences homologous genes. Although the use of siRNAs to silence genes in vertebrate cells was only reported a year ago, the emerging literature indicates that most vertebrate genes can be studied with this technology.

http://facstaff.uwa.edu/dsalter/cell%20biology%20F02/gene%20silency%20review.pdf

Gene silencing in mammals by small interfering RNAs

Mitosis and cytokinesis are undoubtedly the most spectacular parts of the cell cycle. Errors in the choreography of these processes can lead to aneuploidy or genetic instability, fostering cell death or disease. Here, I give an overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission.

Mitotic kinases as regulators of cell division and its checkpoints

Eukaryotic cells replicate by a complex series of evolutionarily conserved events that are tightly regulated at defined stages of the cell division cycle. Progression through this cycle involves a large number of dedicated protein complexes and signaling pathways, and deregulation of this process is implicated in tumorigenesis. We applied high-resolution mass spectrometry-based proteomics to investigate the proteome and phosphoproteome of the human cell cycle on a global scale and quantified 6027 proteins and 20,443 unique phosphorylation sites and their dynamics. Co-regulated proteins and phosphorylation sites were grouped according to their cell cycle kinetics and compared to publicly available messenger RNA microarray data. Most detected phosphorylation sites and more than 20% of all quantified proteins showed substantial regulation, mainly in mitotic cells. Kinase-motif analysis revealed global activation during S phase of the DNA damage response network, which was mediated by phosphorylation by ATM or ATR or DNA-dependent protein kinases. We determined site-specific stoichiometry of more than 5000 sites and found that most of the up-regulated sites phosphorylated by cyclin-dependent kinase 1 (CDK1) or CDK2 were almost fully phosphorylated in mitotic cells. In particular, nuclear proteins and proteins involved in regulating metabolic processes have high phosphorylation site occupancy in mitosis. This suggests that these proteins may be inactivated by phosphorylation in mitotic cells.

Quantitative Phosphoproteomics Reveals Widespread Full Phosphorylation Site Occupancy During Mitosis

mTOR and S6K1 Mediate Assembly of the Translation Preinitiation Complex through Dynamic Protein Interchange and Ordered Phosphorylation Events

Polo-like kinases (Plks) are increasingly recognized as key regulators of mitosis, meiosis and cytokinesis. In agreement with a broad range of proposed functions during cell division, Plks are subject to complex temporal and spatial control. Recent findings are uncovering the mechanisms of Plk regulation, notably their targeting to different cellular structures through interactions with phosphorylated docking proteins. Moreover, information is emerging on the substrate specificity of Plks and the role of individual substrates in M-phase progression.

Polo-like kinases and the orchestration of cell division.

High‐pressure drops characteristic of microchannel heat sinks (MCHS) is an issue that needs to be addressed to reduce the size of heat‐removing devices in compact electronic devices. Supercritical carbon dioxide (s‐CO₂) is a suitable candidate being proposed as an alternative coolant to enhance the cooling of the microchannel heat sink (MCHS), with high heat flux, due to its favorable thermophysical properties near its critical point. In this study, numerical simulations are conducted to evaluate the thermal and hydraulic performance of a channel for a designed heat sink with s‐CO₂ (at constant P=8MPa ) and compare it with conventional liquid coolant (water). The effect of coolants mass flow rate ( ṁ ), channel aspect ratio (AR), and inlet temperatures on the thermal and hydraulic performance of one channel is studied by varying ṁ from 0.004 to 0.03 kg/s and AR from 0.33 to 10. The results show that, for the same aspect ratio, same geometry, and constant heat flux, s‐CO₂ offers a higher overall heat transfer coefficient (32%) with a lower friction factor (pumping power) compared with the water at the same inlet temperature (T = 32°C). The results of pumping power comparison between two coolants reveal that for CO₂ in supercritical conditions ( P=8MPa , T = 32°C), the consumed power varies by change of the aspect ratio, which is 1.85 times lower than water for AR = 0.33 and is 3.6 times higher for AR = 10. However, in the subcooled state, the reverse effect of the aspect ratio is seen.

/pdf/the-cooling-efficiency-of-s-co2-microchannel-heat-sink-1zfe7o1o.pdf

Lionel Arnaud

Papers

The cooling efficiency of s‐CO₂ microchannel heat sink compared with a water‐based design