Photosystem II core phosphorylation and photosynthetic acclimation require two different protein kinases

Illumination changes elicit modifications of thylakoid proteins and reorganization of the photosynthetic machinery. This involves, in the short term, phosphorylation of photosystem II (PSII) and light-harvesting (LHCII) proteins. PSII phosphorylation is thought to be relevant for PSII turnover, whereas LHCII phosphorylation is associated with the relocation of LHCII and the redistribution of excitation energy (state transitions) between photosystems. In the long term, imbalances in energy distribution between photosystems are counteracted by adjusting photosystem stoichiometry. In the green alga Chlamydomonas and the plant Arabidopsis, state transitions require the orthologous protein kinases STT7 and STN7, respectively. Here we show that in Arabidopsis a second protein kinase, STN8, is required for the quantitative phosphorylation of PSII core proteins. However, PSII activity under high-intensity light is affected only slightly in stn8 mutants, and D1 turnover is indistinguishable from the wild type, implying that reversible protein phosphorylation is not essential for PSII repair. Acclimation to changes in light quality is defective in stn7 but not in stn8 mutants, indicating that short-term and long-term photosynthetic adaptations are coupled. Therefore the phosphorylation of LHCII, or of an unknown substrate of STN7, is also crucial for the control of photosynthetic gene expression.     

Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse

Retroviruses, acting as somatic cell insertional mutagens, have been widely used to identify cancer genes in the haematopoietic system and mammary gland. An insertional mutagen for use in other mouse somatic cells would facilitate the identification of genes involved in tumour formation in a wider variety of tissues. Here we report the ability of the Sleeping Beauty transposon to act as a somatic insertional mutagen to identify genes involved in solid tumour formation. A Sleeping Beauty transposon, engineered to elicit loss-of-function or gain-of-function mutations, transposed in all somatic tissues tested and accelerated tumour formation in mice predisposed to cancer. Cloning transposon insertion sites from these tumours revealed the presence of common integration sites, at known and candidate cancer genes, similar to those observed in retroviral mutagenesis screens. Sleeping Beauty is a new tool for unbiased, forward genetic screens for cancer genes in vivo.     

Effects of antithymic reticuloepithelial cells serum on the levels of circulating thymic factor and on the sensitivity to azathioprine of spleen spontaneous rosette-forming cells

Summary Swiss mice treated with an antithymic reticuloepithelial cells serum (ATRES) showed a drastic and prolonged depression of the serum thymic factor. A similar but less pronounced effect was also observed following the administration of the antithymocyte (ATS) and the antilymphocyte (ALS) sera. Conversely, the azathioprine sensitivity of spleen spontaneous rosette-forming cells was highly modified by the ATRES but not by the ATS or the ALS. The probable mechanisms of such effects are discussed.     

An intrinsic mechanism of corticogenesis from embryonic stem cells

The cerebral cortex develops through the coordinated generation of dozens of neuronal subtypes, but the mechanisms involved remain unclear. Here we show that mouse embryonic stem cells, cultured without any morphogen but in the presence of a sonic hedgehog inhibitor, recapitulate in vitro the major milestones of cortical development, leading to the sequential generation of a diverse repertoire of neurons that display most salient features of genuine cortical pyramidal neurons. When grafted into the cerebral cortex, these neurons develop patterns of axonal projections corresponding to a wide range of cortical layers, but also to highly specific cortical areas, in particular visual and limbic areas, thereby demonstrating that the identity of a cortical area can be specified without any influence from the brain. The discovery of intrinsic corticogenesis sheds new light on the mechanisms of neuronal specification, and opens new avenues for the modelling and treatment of brain diseases.     

Whole-genome analysis informs breast cancer response to aromatase inhibition

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.     

Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes

N-methyl-D-aspartate (NMDA) receptors mediate excitatory neurotransmission in the mammalian brain. Two glycine-binding NR1 subunits and two glutamate-binding NR2 subunits each form highly Ca2(+)-permeable cation channels which are blocked by extracellular Mg2(+) in a voltage-dependent manner. Either GRIN2B or GRIN2A, encoding the NMDA receptor subunits NR2B and NR2A, was found to be disrupted by chromosome translocation breakpoints in individuals with mental retardation and/or epilepsy. Sequencing of GRIN2B in 468 individuals with mental retardation revealed four de novo mutations: a frameshift, a missense and two splice-site mutations. In another cohort of 127 individuals with idiopathic epilepsy and/or mental retardation, we discovered a GRIN2A nonsense mutation in a three-generation family. In a girl with early-onset epileptic encephalopathy, we identified the de novo GRIN2A mutation c.1845C>A predicting the amino acid substitution p.N615K. Analysis of NR1-NR2A(N615K) (NR2A subunit with the p.N615K alteration) receptor currents revealed a loss of the Mg2(+) block and a decrease in Ca2(+) permeability. Our findings suggest that disturbances in the neuronal electrophysiological balance during development result in variable neurological phenotypes depending on which NR2 subunit of NMDA receptors is affected.     

Determination of electron orbital magnetic moments in carbon nanotubes

The remarkable transport properties of carbon nanotubes (CNTs) are determined by their unusual electronic structure. The electronic states of a carbon nanotube form one-dimensional electron and hole sub-bands, which, in general, are separated by an energy gap. States near the energy gap are predicted to have an orbital magnetic moment, mu(orb), that is much larger than the Bohr magneton (the magnetic moment of an electron due to its spin). This large moment is due to the motion of electrons around the circumference of the nanotube, and is thought to play a role in the magnetic susceptibility of CNTs and the magnetoresistance observed in large multiwalled CNTs. But the coupling between magnetic field and the electronic states of individual nanotubes remains to be quantified experimentally. Here we report electrical measurements of relatively small diameter (2-5 nm) individual CNTs in the presence of an axial magnetic field. We observe field-induced energy shifts of electronic states and the associated changes in sub-band structure, which enable us to confirm quantitatively the predicted values for mu(orb).     

Soviet psychiatric abuse: allegations met by red tape

Responding to accusations by human rights groups concerning the confinement of dissidents in mental hospitals, the Soviet All-Union Society of Psychiatrists (AUSP) has supplied the World Psychiatric Association (WPA) with data on two alleged cases of abuse and promised information on four more. Some member societies are suspicious that the move is simply a delaying tactic to forestall possible ouster of the AUSP from the WPA. Some members are also concerned that the WPA executive council's "overscrupulous" stance on confidentiality has hindered investigation of complaints of psychiatric abuse.