Integration of TGF-beta and Ras/MAPK signaling through p53 phosphorylation

During development and tissue homeostasis, cells must integrate different signals. We investigated how cell behavior is controlled by the combined activity of transforming growth factor-beta (TGF-beta) and receptor tyrosine kinase (RTK) signaling, whose integration mechanism is unknown. We find that RTK/Ras/MAPK (mitogen-activated protein kinase) activity induces p53 N-terminal phosphorylation, enabling the interaction of p53 with the TGF-beta-activated Smads. This mechanism confines mesoderm specification in Xenopus embryos and promotes TGF-beta cytostasis in human cells. These data indicate a mechanism to allow extracellular cues to specify the TGF-beta gene-expression program.     

Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor

Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.     

Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling

The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance.     

Comparative influence of isolation,landscape, and wetland characteristics on egg-mass abundance of two pool-breeding amphibian species

The distribution and abundance of species are shaped by local and landscape processes, but the dominant processes may differ with scale and increasing human disturbance. We investigated population responses of two pool-breeding amphibian species to differences in local and landscape characteristics in suburbanizing, southeastern New Hampshire, USA. In 2003 and 2004, we sampled 49 vernal pools for spotted salamander (Ambystoma maculatum) and wood frog (Lithobates sylvaticus) egg masses. Using egg masses as a proxy for breeding-female population size, we examined the relative influence of five land-use and three isolation variables at two scales (300 and 1000 m) and five wetland variables on egg-mass abundance. For both species, road density at the landscape scale (1000 m) and hydroperiod most strongly predicted egg-mass abundance, with abundance decreasing as roads became denser and hydroperiods shortened. Wetland isolation was also an important predictor, with abundance greatest at more isolated pools, suggesting that both species concentrate at isolated pools when alternative breeding sites are scarce. Surprisingly, no 300-m parameters were strongly associated with salamander egg-mass abundance, whereas several landscape parameters were. In suburbanizing areas, it is at least as important to consider landscape-scale road density as to consider hydroperiod when designing conservation plans for these species. Furthermore, both isolated and clustered pools provide these species important habitat and may require protection. Finally, the conceptual framework for spotted-salamander management must be expanded so that spatial configuration at the landscape scale becomes a regular, integrated component of conservation planning for this species.     

Management of pelvic trauma: neurological damage, urinary tract disruption and pelvic fractures

PRACTICAL RELEVANCE: Cats commonly present with pelvic trauma following road traffic accidents (RTAs). A logical step-wise approach to diagnostics and subsequent management can significantly improve the prognosis in the majority of cases. This article provides a practical guide to assist decision-making and optimise management of these cats. CLINICAL CHALLENGES: Affected cats may have sustained trauma to several body systems and, hence, their management can be complex, requiring good clinical, diagnostic and surgical skills (often both soft tissue and orthopaedic!). PATIENT GROUP: Any cat allowed access to the outdoors is potentially at risk of being involved in an RTA and sustaining pelvic trauma. Young male cats are most commonly affected. EVIDENCE BASE: Many original articles and textbook chapters have been published on aspects of pelvic trauma. However, to the authors' knowledge, this is the first comprehensive overview of the assessment and management of the feline pelvic trauma case. The review begins by discussing initial triage and neurological examination, and then focuses, in turn, on assessment and management of the 'tail pull' injury, the diagnosis and management of urinary tract rupture, and the approach to managing specific pelvic fractures.     

Exploration of plant genomes in the FLAGdb++ environment

Background

Efficient high throughput screening systems of useful mutants are prerequisite for study of plant functional genomics and lots of application fields. Advance in such screening tools, thanks to the development of analytic instruments. Direct analysis in real-time (DART)-mass spectrometry (MS) by ionization of complex materials at atmospheric pressure is a rapid, simple, high-resolution analytical technique. Here we describe a rapid, simple method for the genetic discrimination of intact Arabidopsis thaliana mutant seeds using metabolic profiling by DART-MS.

Results

To determine whether this DART-MS combined by multivariate analysis can perform genetic discrimination based on global metabolic profiling, intact Arabidopsis thaliana mutant seeds were subjected to DART-MS without any sample preparation. Partial least squares-discriminant analysis (PLS-DA) of DART-MS spectral data from intact seeds classified 14 different lines of seeds into two distinct groups: Columbia (Col-0) and Landsberg erecta (Ler) ecotype backgrounds. A hierarchical dendrogram based on partial least squares-discriminant analysis (PLS-DA) subdivided the Col-0 ecotype into two groups: mutant lines harboring defects in the phenylpropanoid biosynthetic pathway and mutants without these defects. These results indicated that metabolic profiling with DART-MS could discriminate intact Arabidopsis seeds at least ecotype level and metabolic pathway level within same ecotype.

Conclusion

The described DART-MS combined by multivariate analysis allows for rapid screening and metabolic characterization of lots of Arabidopsis mutant seeds without complex metabolic preparation steps. Moreover, potential novel metabolic markers can be detected and used to clarify the genetic relationship between Arabidopsis cultivars. Furthermore this technique can be applied to predict the novel gene function of metabolic mutants regardless of morphological phenotypes.     

Studies on the development of a mating disruption system to control the tomato leafminer, Tuta absoluta Povolny (Lepidoptera: Gelechiidae)

BACKGROUND: The tomato leafminer (Tuta absoluta Povolny) has rapidly colonised the whole Mediterranean and South‐Atlantic coasts of Spain, and it has become a key problem in both outdoor and greenhouse crops. New control methods compatible with biological control are required, and mating disruption appears to be a perfect method in current agriculture, as it is an environmentally friendly and residue‐free technique. IPM packages tested have included the use of pheromones to detect populations, but there has not been much previous research on mating disruption of T. absoluta. In this work, pheromone doses varying from 10 to 40 g ha^?1, emitted at a constant rate over 4 months, were tested in greenhouses with different levels of containment in order to evaluate the efficacy of mating disruption on T. absoluta. RESULTS: Trials on containment level revealed that the flight of T. absoluta was satisfactorily disrupted with an initial pheromone dose of 30 g ha^?1, and levels of damage did not significantly differ from those in reference plots with insecticide treatments. Later efficacy trials confirmed previous experiences, and release studies showed that control of damage and flight disruption were taking place when releasing at least 85 mg pheromone per ha per day. CONCLUSION: Effective control using pheromone application against T. absoluta can be achieved, in greenhouses with high containment levels, for 4 months, with initial doses of 30 g ha^?1. Further research must be conducted in order to evaluate the prospect of outdoor application of mating disruption systems. Copyright © 2011 Society of Chemical Industry