Time to articulate a vision for the future of plant proteomics - A global perspective: An initiative for establishing the International Plant Proteomics Organization (INPPO)

Given the essential role of proteomics in understanding the biology of plants, we are establishing a global plant proteomics organization to properly organize, preserve and disseminate collected information on plant proteomics. We call this organization 'International Plant Proteomics Organization (INPPO; http://www.inppo.com).' Ten initiatives of INPPO are outlined along with how to address them in multiple phases. As our vision is global, we sincerely hope the scientific communities around the world will come together to support and join INPPO.     

Antitumor efficacy of a thrombospondin 1 mimetic CovX-body

CVX-045 is produced by covalently attaching a thrombospondin 1 (TSP-1) mimetic comprising a peptidic sequence and a linker to the Fab binding site of a proprietary scaffold antibody. CVX-045 possesses the potency of the TSP-1-derived peptide, along with the advantageous pharmacokinetics of an antibody. Antitumor activity of CVX-045 was evaluated in human xenograft models alone and in combination with standard chemotherapies and targeted molecules. In A549 and A431 xenograft models, CVX-045 demonstrated significant (P < .05) antiangiogenic activity, reducing tumor microvessel density and increasing the levels of necrosis within treated tumors. In an HT-29 xenograft model, CVX-045 in combination with 5-fluorouracil significantly (P < .01) decreased tumor growth rate compared with vehicle, CVX-045, or 5-fluorouracil alone. Cotreatment of CVX-045 plus CPT-11 delayed progression of tumor growth from day 28 to 60. In contrast CVX-045 alone treatment did not delay the progression of tumor growth, and CPT-11 alone delayed progression of tumor growth to day 39. Cotreatment of CVX-045 with sunitinib extended the time to reach tumor load from day 26 to 40. In summary, CVX-045 exhibits significant antiangiogenic activity in several tumor models and enhances antitumor activity in combination with chemotherapy or targeted therapies. These data suggest future avenues for effective combination therapy in treating solid tumors. CVX-045 has recently completed a phase 1 trial in solid tumors where it has been well tolerated.     

Factors influencing the seasonal life history of the pitcher-plant mosquito, Wyeomyia smithii

Abstract.  1. The effects of resource levels, thermal microclimate, and seasonal oviposition patterns on fecundity and survivorship in the pitcher-plant mosquito, Wyeomyia smithii (Coq.), were examined at a northern Wisconsin bog over the course of 2 years. Wyeomyia smithii are bivoltine at this locality, thereby enabling the study of summer and overwintering generations separately.
2. Nutrient resources of W. smithii were not limiting and there was no indication of density-dependent survivorship or fecundity.
3. Oviposition rates were highest in young, large pitchers and individual mosquitoes appeared to allocate only a few eggs to any one leaf.
4. Winter was the harsh season, and the principal manifestation of seasonal harshness was reduced survivorship.
5. Overwintering W. smithii that had been oviposited later in the summer had a higher odds of survival than those oviposited earlier in the summer.
6. It was concluded that dispersal of eggs among many pitchers serves to spread the risk of encountering lethal winter temperatures among spatially unpredictable patches.     

Cost-effective application of pulsed-field gel electrophoresis to typing of Salmonella enterica Serovar Typhimurium

Salmonella enterica serovar Typhimurium is frequently isolated from humans and animals. Phage typing is historically the first-line reference typing technique in Europe. It is rapid and convenient for laboratories with appropriate training and experience, and costs of consumables are low. Phage typing and pulsed-field gel electrophoresis (PFGE) were performed on 503 isolates of serovar Typhimurium. Twenty-nine phage types and 53 PFGE patterns were observed. Most isolates of phage types DT104, DT104b, and U310 are not distinguishable from other members of their phage type by PFGE. By contrast, PFGE of isolates of phage types DT193 and U302 shows great heterogeneity. Analysis of experience with PFGE and phage typing can facilitate the selective application of PFGE to maximize the yield of epidemiologically relevant additional information while controlling costs.     

Resource partitioning through oceanic segregation of foraging juvenile southern elephant seals (<Emphasis Type="Italic">Mirounga leonina</Emphasis>)

In highly dynamic and unpredictable environments such as the Southern Ocean, species that have evolved behaviors that reduce the effects of intra-specific competition may have a selective advantage. This is particularly true when juveniles face disadvantages when foraging due to morphological or physiological limitation, which is the case for many marine mammals. We tracked the at-sea movements of 48 juvenile southern elephant seals (Mirounga leonina) between the ages of 1 and 4 years from the population at Macquarie Island using locations derived from recorded light levels. There were significant differences in the total amount of the Southern Ocean covered by the different age-groups. The younger seals used a smaller area than the older seals. On average, the younger individuals also made more trips to sea than the older seals and did not travel as far on each trip. Females spent more time at sea than males and there were no significant differences between the total areas used by male and females. In summary, younger seals remained closer to the island at all times, and they spent more time in more northerly regions that older seals. These differences in behavior created temporal and spatial segregation between juveniles of different ages. Therefore, we suggest that these temporal and spatial separations help to avoid intra-specific competition for resources on land, space on beaches, and at-sea foraging areas. Such modifications of haul-out timing and behavior enable them to exploit a patchy and unpredictable environment.     

Membrane-bound ARF1 peptide: interpretation of neutron diffraction data by molecular dynamics simulation methods

Adenosine diphosphate ribosylation factor-1 (ARF1) is activated by cell membrane binding of a self-folding N-terminal domain. We have previously presented four possible conformations of the membrane bound, human ARF1 N-terminal peptide in planar lipid bilayers of DOPC and DOPG (7:3 molar ratio), determined from lamellar neutron diffraction and circular dichroism data. In this paper we analyse the four possible conformations by molecular dynamics simulations. The aim of these simulations was to use MD to distinguish which of the four possible membrane bound structures was the most likely. The most likely conformation was determined according to the following criteria: (a) location of label positions on the peptide in relation to the bilayer, (b) lowest mean square displacement from the initial structure, (c) lowest system energy, (d) most peptide-lipid headgroup hydrogen bonding, (e) analysis of phi/psi angles of the peptide. These findings demonstrate the application of molecular dynamics simulations to explore neutron diffraction data.     

Periodic variability in cetacean strandings: links to large-scale climate events

Cetacean strandings elicit much community and scientific interest, but few quantitative analyses have successfully identified environmental correlates to these phenomena. Data spanning 1920-2002, involving a total of 639 stranding events and 39 taxa groups from southeast Australia, were found to demonstrate a clear 11-13- year periodicity in the number of events through time. These data positively correlated with the regional persistence of both zonal (westerly) and meridional (southerly) winds, reflecting general long-term and large-scale shifts in sea-level pressure gradients. Periods of persistent zonal and meridional winds result in colder and presumably nutrient-rich waters being driven closer to southern Australia, resulting in increased biological activity in the water column during the spring months. These observations suggest that large-scale climatic events provide a powerful distal influence on the propensity for whales to strand in this region. These patterns provide a powerful quantitative framework for testing hypotheses regarding environmental links to strandings and provide managers with a potential predictive tool to prepare for years of peak stranding activity.     

A structural study of the myristoylated N-terminus of ARF1

The effect of myristoylation on the 15-amino-acid peptide from the membrane-binding N-terminus of ADP ribosylation factor 1 (ARF1) was studied using neutron diffraction and circular dichroism. A previous study on the non-acylated form indicated that the peptide lies parallel to the membrane, at a shallow depth and in the vicinity of the phosphorylcholine headgroups. It was suggested that the helix does not extend past residue 12, an important consequence for the linking region of the ARF1 protein. In this paper, we show that the result of myristoylation is to increase the helical content reaching the peptide's C-terminus, resulting in the formation of a new hydrophobic face. This increased helicity may augment the entire protein's membrane-binding affinity, indicating that ARF1 effectively has two interdependent membrane-binding motifs.     

T antigen origin-binding domain of simian virus 40: determinants of specific DNA binding

To better understand origin recognition and initiation of DNA replication, we have examined by NMR complexes formed between the origin-binding domain of SV40 T antigen (T-ag-obd), the initiator protein of the SV40 virus, and cognate and noncognate DNA oligomers. The results reveal two structural effects associated with "origin-specific" binding that are absent in nonspecific DNA binding. The first is the formation of a hydrogen bond (H-bond) involving His 203, a residue that genetic studies have previously identified as crucial to both specific and nonspecific DNA binding in full-length T antigen. In free T-ag-obd, the side chain of His 203 has a pK(a) value of approximately 5, titrating to the N(epsilon)(1)H tautomer at neutral pH (Sudmeier, J. L., et al. (1996) J. Magn. Reson., Ser. B 113, 236-247). In complexes with origin DNA, His 203 N(delta)(1) becomes protonated and remains nontitrating as the imidazolium cation at all pH values from 4 to 8. The H-bonded N(delta1)H resonates at 15.9 ppm, an unusually large N-H proton chemical shift, of a magnitude previously observed only in the catalytic triad of serine proteases at low pH. The formation of this H-bond requires the middle G/C base pair of the recognition pentanucleotide, GAGGC. The second structural effect is a selective distortion of the A/T base pair characterized by a large (0.6 ppm) upfield chemical-shift change of its Watson-Crick proton, while nearby H-bonded protons remain relatively unaffected. The results indicate that T antigen, like many other DNA-binding proteins, may employ "catalytic" or "transition-state-like" interactions in binding its cognate DNA (Jen-Jacobson, L. (1997) Biopolymers 44, 153-180), which may be the solution to the well-known paradox between the relatively modest DNA-binding specificity exhibited by initiator proteins and the high specificity of initiation.     

Feeding preferences in 2 disjunct populations of tiger snakes, Notechis scutatus (Elapidae)

Variations at both the genetic and phenotypic levels play animportant role in responses to food and food-related stimuli.Knowledge of such variations is crucial to understanding howpopulations adapt to changing environments. We investigatedthe dietary preferences of 2 tiger snake populations and comparedthe responses of diet-naive animals (laboratory-born neonates),diet-controlled animals (laboratory-reared juveniles), and naturaldiet–experienced animals (wild-caught adults) to visualand chemical cues from 6 prey types (mouse, skink, silver gull,chicken, shearwater, and frog). The mainland population inhabitsa swamp, feeds mostly on frogs, and suffers heavy predation.The second population inhabits a small nearby offshore islandwith no standing water (no frogs); feeds mostly on skinks, mice,and, as adults, silver gull chicks; and suffers no known predation.Although different prey are eaten in the 2 populations, adultwild-caught snakes from both populations showed a significantpreference for 3 types of prey (frog, mouse, and chick), irrespectiveof their natural diet. Neonates responded to all prey cues morethan they did to control stimuli in both populations. However,the island neonates showed significantly higher interest insilver gull chick stimuli (the main prey of the island adultsnakes) than did their mainland conspecifics. Laboratory-bredjuveniles displayed behavioral plasticity by significantly increasingtheir response to mice after being fed baby mice for 7 months.We conclude that genetic-based differences in food-related cuesare important in tiger snakes but that they are also capableof behavioral plasticity. Island adult and neonate snakes exhibitedresponses to prey types no longer consumed naturally (frog),suggesting that behavioral characters may have been retainedfor long periods under relaxed selection. Island neonates showeda strong interest in a novel prey item (silver gull). This resultcomplements previous work describing how island snakes havedeveloped the ability to swallow larger prey than usual, aswell as seemingly developing a taste for them.