Functional inactivation of a fraction of excitatory synapses in mice deficient for the active zone protein bassoon

Mutant mice lacking the central region of the presynaptic active zone protein Bassoon were generated to establish the role of this protein in the assembly and function of active zones as sites of synaptic vesicle docking and fusion. Our data show that the loss of Bassoon causes a reduction in normal synaptic transmission, which can be attributed to the inactivation of a significant fraction of glutamatergic synapses. At these synapses, vesicles are clustered and docked in normal numbers but are unable to fuse. Phenotypically, the loss of Bassoon causes spontaneous epileptic seizures. These data show that Bassoon is not essential for synapse formation but plays an essential role in the regulated neurotransmitter release from a subset of glutamatergic synapses.     

Influence of personal characteristics of individual women on sensitivity and specificity of mammography in the Million Women Study: cohort study

Objectives To examine how lifestyle, hormonal, and other factors influence the sensitivity and specificity of mammography.Methods Women recruited into the Million Women Study completed a questionnaire about various personal factors before routine mammographic screening. A sample of 122 355 women aged 50-64 years were followed for outcome of screening and incident breast cancer in the next 12 months. Sensitivity and specificity were calculated by using standard definitions, with adjustment for potential confounding factors.Results Breast cancer was diagnosed in 726 (0.6%) women, 629 in screen positive and 97 in screen negative women; 3885 (3.2%) were screen positive but had no subsequent diagnosis of breast cancer. Overall sensitivity was 86.6% and specificity was 96.8%. Three factors had an adverse effect on both measures: use of hormone replacement therapy (sensitivity: 83.0% (95% confidence interval 77.4% to 87.6%), 84.7% (73.9% to 91.6%), and 92.1% (87.6% to 95.0%); specificity: 96.8% (96.6% to 97.0%), 97.8% (97.5% to 98.0%), and 98.1% (98.0% to 98.2%), respectively, for current, past, and never use); previous breast surgery v no previous breast surgery (sensitivity: 83.5% (75.7% to 89.1%) v 89.4% (86.5% to 91.8%); specificity: 96.2% (95.8% to 96.5%) v 97.4% (97.3% to 97.5%), respectively); and body mass index < 25 v ≥ 25 (sensitivity: 85.7% (81.2% to 89.3%) v 91.0% (87.5% to 93.6%); specificity: 97.2% (97.0% to 97.3%) v 97.4% (97.3% to 97.6%), respectively). Neither sensitivity nor specificity varied significantly according to age, family history of breast cancer, parity, past oral contraceptive use, tubal ligation, physical activity, smoking, or alcohol consumption.Conclusions The efficiency, and possibly the effectiveness, of mammographic screening is lower in users of hormone replacement therapy, in women with previous breast surgery, and in thin women compared with other women.     

Analysis of the role of COMATOSE and peroxisomal beta-oxidation in the determination of germination potential in Arabidopsis

Comparative physiological analysis of mutant Arabidopsis seeds under defined environmental conditions was used to analyse the relative contributions of components of peroxisomal beta-oxidation in the control of seed germination potential. The COMATOSE (CTS) and KAT2 loci were shown to play essential roles in regulating germination and establishment potentials, whereas LACS6 and LACS7 loci only influenced establishment following germination. The viability and desiccation tolerance of three different mutant alleles of CTS were shown to be intermediate between that of dormant and non-dormant wild-type seeds. Analysis of ttg-1 cts-1 double mutant seeds demonstrated that the cts lesion did not influence after-ripening capacity. These data demonstrate the importance of peroxisomal beta-oxidation in the control of germination potential, but suggest that breakdown of stored lipid is not an important prerequisite for germination. A function is suggested for CTS following after-ripening within pathways related to the progression of germination prior to radicle emergence.     

Protein synthesis-dependent long-term functional plasticity: methods and techniques

There is growing interest in late-LTP and late-LTD, that is, distinct forms of functional plasticity that require somatic functions such as protein synthesis in addition to the transient synaptic processes that are required for short lasting forms. Interestingly, to date only these forms of lasting plastic events could be detected in healthy, freely moving animals and thus, they are considered as physiological cellular models of learning and memory formation. Late-LTP and -LTD are characterized by 'synaptic tagging' or 'capture' and 'synaptic cross-tagging', but there are only a few laboratories that can currently perform experiments studying these properties. In brain slice work, there are many different approaches to investigate these processes using different methodological variations: some allow slices to rest for long periods before the experiment starts, others do not; some run their experiments at near to physiological temperatures, others at lower temperatures; some stimulate frequently, others do not.     

Glucosinolate biochemical diversity and innovation in the Brassicales

Glucosinolates were analysed from herbarium specimens and living tissues from representative of all families of the Brassicales, following the phylogenetic schemes of Rodman et al. (1998) and Hall et al. (2002, 2004), including specimens of Akania, Setchellanthus, Emblingia, Stixis, Forchhammeria and members of the Capparaceae for which glucosinolate content had not previously been reported. The results are reviewed along with additional published data on glucosinolate content of members of the Brassicales. In addition to providing an overview of the evolution of glucosinolate biochemical diversity within the core Brassicales, there were three main findings. Firstly, the glucosinolate content of some 'orphan' taxa of the Brassicales, such as Setchellanthus and Emblingia were consistent with recent phylogentic analyses based upon DNA sequence comparisons, while further analyses of Tirania and Stixis is required. Secondly, methyl glucosinolate is found within the Capparaceae and Cleomaceae, but also, unexpectedly, within Forchhammeria, with implications for the biochemical and evolutionary origin of methyl glucosinolate and the phylogenetic relationships of Forchhammeria. Thirdly, whereas Old World Capparaceae contain methyl glucosinolate, New World Capparaceae, including New World Capparis, either contain methyl glucosinolates or glucosinolates of complex and unresolved structures, indicative of continued innovation in glucosinolate biosynthesis. These taxa may be productive sources of glucosinolate biosynthetic genes and alleles that are not found in the model plant Arabidopsis thaliana.