On the nature of biological clocks?

Zusammenfassung Feststellung, dass schlafende Goldhamster einen höheren ATP-Gehalt in Gehirn und Leber besitzen als wache Tiere und dass Zeitgeber, wie Licht und Temperatur, sowohl Zellviskosität als auch ATP-Niveau verändern.     

Replacing the complementarity-determining regions in a human antibody with those from a mouse

The variable domains of an antibody consist of a beta-sheet framework with hypervariable regions (or complementarity-determining regions--CDRs) which fashion the antigen-binding site. Here we attempted to determine whether the antigen-binding site could be transplanted from one framework to another by grafting the CDRs. We substituted the CDRs from the heavy-chain variable region of mouse antibody B1-8, which binds the hapten NP-cap (4-hydroxy-3-nitrophenacetyl caproic acid; KNP-cap = 1.2 microM), for the corresponding CDRs of a human myeloma protein. We report that in combination with the B1-8 mouse light chain, the new antibody has acquired the hapten affinity of the B1-8 antibody (KNP-cap = 1.9 microM). Such 'CDR replacement' may offer a means of constructing human monoclonal antibodies from the corresponding mouse monoclonal antibodies.     

A continuous-wave Raman silicon laser

Achieving optical gain and/or lasing in silicon has been one of the most challenging goals in silicon-based photonics because bulk silicon is an indirect bandgap semiconductor and therefore has a very low light emission efficiency. Recently, stimulated Raman scattering has been used to demonstrate light amplification and lasing in silicon. However, because of the nonlinear optical loss associated with two-photon absorption (TPA)-induced free carrier absorption (FCA), until now lasing has been limited to pulsed operation. Here we demonstrate a continuous-wave silicon Raman laser. Specifically, we show that TPA-induced FCA in silicon can be significantly reduced by introducing a reverse-biased p-i-n diode embedded in a silicon waveguide. The laser cavity is formed by coating the facets of the silicon waveguide with multilayer dielectric films. We have demonstrated stable single mode laser output with side-mode suppression of over 55 dB and linewidth of less than 80 MHz. The lasing threshold depends on the p-i-n reverse bias voltage and the laser wavelength can be tuned by adjusting the wavelength of the pump laser. The demonstration of a continuous-wave silicon laser represents a significant milestone for silicon-based optoelectronic devices.     

DNA sequence and analysis of human chromosome 9

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.     

The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore

A sudden increase in permeability of the inner mitochondrial membrane, the so-called mitochondrial permeability transition, is a common feature of apoptosis and is mediated by the mitochondrial permeability transition pore (mtPTP). It is thought that the mtPTP is a protein complex formed by the voltage-dependent anion channel, members of the pro- and anti-apoptotic BAX-BCL2 protein family, cyclophilin D, and the adenine nucleotide (ADP/ATP) translocators (ANTs). The latter exchange mitochondrial ATP for cytosolic ADP and have been implicated in cell death. To investigate the role of the ANTs in the mtPTP, we genetically inactivated the two isoforms of ANT in mouse liver and analysed mtPTP activation in isolated mitochondria and the induction of cell death in hepatocytes. Mitochondria lacking ANT could still be induced to undergo permeability transition, resulting in release of cytochrome c. However, more Ca2+ than usual was required to activate the mtPTP, and the pore could no longer be regulated by ANT ligands. Moreover, hepatocytes without ANT remained competent to respond to various initiators of cell death. Therefore, ANTs are non-essential structural components of the mtPTP, although they do contribute to its regulation.