Id1 restrains p21 expression to control endothelial progenitor cell formation

Loss of Id1 in the bone marrow (BM) severely impairs tumor angiogenesis resulting in significant inhibition of tumor growth. This phenotype has been associated with the absence of circulating endothelial progenitor cells (EPCs) in the peripheral blood of Id1 mutant mice. However, the manner in which Id1 loss in the BM controls EPC generation or mobilization is largely unknown. Using genetically modified mouse models we demonstrate here that the generation of EPCs in the BM depends on the ability of Id1 to restrain the expression of its target gene p21. Through a series of cellular and functional studies we show that the increased myeloid commitment of BM stem cells and the absence of EPCs in Id1 knockout mice are associated with elevated p21 expression. Genetic ablation of p21 rescues the EPC population in the Id1 null animals, re-establishing functional BM-derived angiogenesis and restoring normal tumor growth. These results demonstrate that the restraint of p21 expression by Id1 is one key element of its activity in facilitating the generation of EPCs in the BM and highlight the critical role these cells play in tumor angiogenesis.     

The abp gene in Geobacillus stearothermophilus T-6 encodes a GH27 β-L-arabinopyranosidase

In this study we demonstrate that the abp gene in Geobacillus stearothermophilus T-6 encodes a family 27 glycoside hydrolase β-L-arabinopyranosidase. The catalytic constants towards the chromogenic substrate pNP-β-L-arabinopyranoside were 0.8±0.1 mM, 6.6±0.3 s(-1), and 8.2±0.3 s(-1) mM(-1) for K(m), k(cat) and k(cat)/K(m), respectively. (13)C NMR spectroscopy unequivocally showed that Abp is capable of removing β-L-arabinopyranose residues from the natural arabino-polysaccharide, larch arabinogalactan. Most family 27 enzymes are active on galactose and contain a conserved Asp residue, whereas in Abp this residue is Ile67, which shifts the specificity of the enzyme towards arabinopyranoside.     

Failure of the Tomato Trans-Acting Short Interfering RNA Program to Regulate AUXIN RESPONSE FACTOR3 and ARF4 Underlies the Wiry Leaf Syndrome

Interfering with small RNA production is a common strategy of plant viruses. A unique class of small RNAs that require microRNA and short interfering (siRNA) biogenesis for their production is termed trans-acting short interfering RNAs (ta-siRNAs). Tomato (Solanum lycopersicum) wiry mutants represent a class of phenotype that mimics viral infection symptoms, including shoestring leaves that lack leaf blade expansion. Here, we show that four WIRY genes are involved in siRNA biogenesis, and in their corresponding mutants, levels of ta-siRNAs that regulate AUXIN RESPONSE FACTOR3 (ARF3) and ARF4 are reduced, while levels of their target ARFs are elevated. Reducing activity of both ARF3 and ARF4 can rescue the wiry leaf lamina, and increased activity of either can phenocopy wiry leaves. Thus, a failure to negatively regulate these ARFs underlies tomato shoestring leaves. Overexpression of these ARFs in Arabidopsis thaliana, tobacco (Nicotiana tabacum), and potato (Solanum tuberosum) failed to produce wiry leaves, suggesting that the dramatic response in tomato is exceptional. As negative regulation of orthologs of these ARFs by ta-siRNA is common to land plants, we propose that ta-siRNA levels serve as universal sensors for interference with small RNA biogenesis, and changes in their levels direct species-specific responses.     

Universal florigenic signals triggered by FT homologues regulate growth and flowering cycles in perennial day-neutral tomato

The transition from vegetative to floral meristems in higher plants is programmed by the coincidence of internal and environmental signals. Classic grafting experiments have shown that leaves, in response to changing photoperiods, emit systemic signals, dubbed 'florigen', which induce flowering at the shoot apex. The florigen paradigm was conceived in photoperiod-sensitive plants: nevertheless it implies that although activated by different stimuli in different flowering systems, the signal is common to all plants. Tomato is a day-neutral, perennial plant, with sympodial and modular organization of its shoots and thus with reiterative regular vegetative/reproductive transitions. SINGLE FLOWER TRUSS a regulator of flowering-time and shoot architecture encodes the tomato orthologue of FT, a major flowering integrator gene in Arabidopsis. SFT generates graft-transmissible signals which complement the morphogenetic defects in sft plants, substitute for light dose stimulus in tomato and for contrasting day-length requirements in Arabidopsis and MARYLAND MAMMOTH tobacco. It is discussed how systemic signals initiated by SFT interact with the SELF PRUNING gene to regulate vegetative to reproductive (V/R) transitions in the context of two flowering systems, one for primary apices and the other for sympodial shoots.     

Effects of productivity and disturbance on species richness: a neutral model

Productivity and disturbance are major determinants of species diversity, and results from theoretical models predict that species richness should peak at intermediate levels of both factors. Such "unimodal" responses have been documented in many field and laboratory studies and have usually been attributed to differences among species in competitive ability and/or trade-offs between competitive ability and tolerance to disturbance. Here we show that most documented patterns of disturbance-richness and productivity-richness relationships, as well as the observed interactions between the two factors, can be explained by a simple neutral model where all species are ecologically identical and lack trade-offs in species characteristics. This finding suggests that current neutral theories can be extended to explain patterns of species responses to productivity and disturbance.     

The significance of telomeric aggregates in the interphase nuclei of tumor cells

Telomeres are TTAGGG repetitive motifs found at the ends of vertebrate chromosomes. In humans, telomeres are protected by shelterin, a complex of six proteins (de Lange [2005] Genes Dev. 19: 2100-2110). Since (Müller [1938] Collecting Net. 13: 181-198; McClintock [1941] Genetics 26: 234-282), their function in maintaining chromosome stability has been intensively studied. This interest, especially in cancer biology, stems from the fact that telomere dysfunction is linked to genomic instability and tumorigenesis (Gisselsson et al. [2001] Proc. Natl. Acad. Sci. USA 98: 12683-12688; Deng et al. [2003] Genes Chromosomes Cancer 37: 92-97; DePinho and Polyak [2004] Nat. Genetics 36: 932-934; Meeker et al. [2004] Clin. Cancer Res. 10: 3317-3326). In the present overview, we will discuss the role of telomeres in genome stability, recent findings on three-dimensional (3D) changes of telomeres in tumor interphase nuclei, and outline future avenues of research.     

Silencing of a single gene in tomato plants resistant to Tomato yellow leaf curl virus renders them susceptible to the virus

A reverse-genetics approach was applied to identify genes involved in Tomato yellow leaf curl virus (TYLCV) resistance, taking advantage of two tomato inbred lines from the same breeding program—one susceptible (S), one resistant (R—that used Solanum habrochaites as the source of resistance. cDNA libraries from inoculated and non-inoculated R and S plants were compared, postulating that genes preferentially expressed in the R line may be part of the network sustaining resistance to TYLCV. Further, we assumed that silencing genes located at important nodes of the network would lead to collapse of resistance. Approximately 70 different cDNAs representing genes preferentially expressed in R plants were isolated and their genes identified by comparison with public databases. A Permease I-like protein gene encoding a transmembranal transporter was further studied: it was preferentially expressed in R plants and its expression was enhanced several-fold following TYLCV inoculation. Silencing of the Permease gene of R plants using Tobacco rattle virus-induced gene silencing led to loss of resistance, expressed as development of disease symptoms typical of infected susceptible plants and accumulation of large amounts of virus. Silencing of another membrane protein gene preferentially expressed in R plants, Pectin methylesterase, previously shown to be involved in Tobacco mosaic virus translocation, did not lead to collapse of resistance of R plants. Thus, silencing of a single gene can lead to collapse of resistance, but not every gene preferentially expressed in the R line has the same effect, upon silencing, on resistance.     

Balint groups as 'shared care' in the area of mental health in primary medicine

This paper describes how Balint groups can be effective for primary care doctors and how leaders of these groups can act as role models in the interdisciplinary, experiential learning experience. The paper describes the way Balint activity helps the facilitation of a dialogue between mental health professionals and primary care physicians. While these groups have been found to improve the sensitivity of doctors in their interaction with patients, Balint groups, with the joint leadership of professionals from different disciplines, can be seen as an effective method to improve primary care and mental health cooperation. These issues are discussed and appropriate examples outlined offering an uncommon perspective on an interesting topic to promote an integrated, shared model of care.     

Differences in Context and Feedback Result in Different Trajectories and Adaptation Strategies in Reaching

Computational models of motor control have often explained the straightness of horizontal planar reaching movements as a consequence of optimal control. Departure from rectilinearity is thus regarded as sub-optimal. Here we examine if subjects may instead select to make curved trajectories following adaptation to force fields and visuomotor rotations. Separate subjects adapted to force fields with or without visual feedback of their hand trajectory and were retested after 24 hours. Following adaptation, comparable accuracies were achieved in two ways: with visual feedback, adapted trajectories in force fields were straight whereas without it, they remained curved. The results suggest that trajectory shape is not always straight, but is also influenced by the calibration of available feedback signals for the state estimation required by the task. In a follow-up experiment, where additional subjects learned a visuomotor rotation immediately after force field, the trajectories learned in force fields (straight or curved) were transferred when directions of the perturbations were similar but not when directions were opposing. This demonstrates a strong bias by prior experience to keep using a recently acquired control policy that continues to produce successful performance inspite of differences in tasks and feedback conditions. On relearning of force fields on the second day, facilitation by intervening visuomotor rotations occurred only when required motor adjustments and calibration of feedback signals were similar in both tasks. These results suggest that both the available feedback signals and prior history of learning influence the choice and maintenance of control policy during adaptations.     

LKB1 Regulates Pancreatic β Cell Size, Polarity, and Function

Pancreatic β cells, organized in the islets of Langerhans, sense glucose and secrete appropriate amounts of insulin. We have studied the roles of LKB1, a conserved kinase implicated in the control of cell polarity and energy metabolism, in adult β cells. LKB1-deficient β cells show a dramatic increase in insulin secretion in vivo. Histologically, LKB1-deficient β cells have striking alterations in the localization of the nucleus and cilia relative to blood vessels, suggesting a shift from hepatocyte-like to columnar polarity. Additionally, LKB1 deficiency causes a 65% increase in β cell volume. We show that distinct targets of LKB1 mediate these effects. LKB1 controls β cell size, but not polarity, via the mTOR pathway. Conversely, the precise position of the β cell nucleus, but not cell size, is controlled by the LKB1 target Par1b. Insulin secretion and content are restricted by LKB1, at least in part, via AMPK. These results expose a molecular mechanism, orchestrated by LKB1, for the coordinated maintenance of β cell size, form, and function.