The signaling function of an extra‐floral display: what selects for signal development?

The vertical inflorescences of the Mediterranean annual Salvia viridis carry many small, colorful flowers, and are frequently terminated by a conspicuous tuft of colorful leaves ('flag') that attracts insect visitors. Insects may use the flags as indicators of food rewards in the inflorescences below, as long-distance cues for locating and choosing flowering patches, or both. Clipping of all flags from patches of inflorescences in the field reduced the number of arriving insects, but not the total number of inflorescences and flowers visited by them. The number of flowers visited per inflorescence increased with inflorescence size, and inflorescence and flower visits rates significantly increased with patch size. Six percent of the plants in the study population did not develop any flag during blooming, yet suffered no reduction in seed set as compared to flag-bearing neighboring individuals. Removal of flags from all inflorescences in a patch reduced seed set in comparison with untreated controls, while flag clipping from ten randomly selected inflorescences in a patch did not decrease seed production. These results suggest that flags signal long-distance information to potential pollinators (possibly indicating patch location or size), while flower-related cues may indicate inflorescence quality.
Plants that do not develop flags probably benefit from the flag signals displayed by their neighbors, without bearing the costs of signal production. Greenhouse-grown S. viridis plants allocated a low proportion of their biomass to flags. Plants grown under water stress did not reduce biomass allocation to flags as compared to irrigated controls. Water loss rates of picked flags were lower than those of picked leaves. These findings suggest that the expenses of flag production and maintenance are modest, reducing the selective advantage of individuals that do not carry flags. We discuss additional potential evolutionary mechanisms that may select for flag production.     

Elevational range and timing of breeding in the birds of Ladakh: the effects of body mass, status and diet

We studied the effects of body mass, status (resident or migratory) and diet on the breeding elevation range and timing of reproduction of the birds in the Trans-Himalayan region of Ladakh, northwestern India. Most of breeding birds of Ladakh are Palearctic or breed at high elevations in the mountains. There is a small proportion of Oriental species, and no bird is endemic to this region. We found that heavier birds tended to start their egg-laying earlier than lighter ones. Since body mass is related to the length of incubation and nesting periods, it would appear that one result of this phenomenon is that the time of peak demand for food for most birds coincides with peak food abundance in summer. Status affected the elevation of the breeding range, with resident birds tending to breed at higher elevations than summer visitors. Residents and summer breeders also differed significantly in their diet composition, with the former feeding mainly on plants and seeds, and the latter feeding on molluscs, insects and worms.     

An Adequately Robust Early TNF-α Response Is a Hallmark of Survival Following Trauma/Hemorrhage

Background

Trauma/hemorrhagic shock (T/HS) results in cytokine-mediated acute inflammation that is generally considered detrimental.

Methodology/Principal Findings

Paradoxically, plasma levels of the early inflammatory cytokine TNF-α (but not IL-6, IL-10, or NO₂ ^-/NO₃ ^-) were significantly elevated within 6 h post-admission in 19 human trauma survivors vs. 4 non-survivors. Moreover, plasma TNF-α was inversely correlated with Marshall Score, an index of organ dysfunction, both in the 23 patients taken together and in the survivor cohort. Accordingly, we hypothesized that if an early, robust pro-inflammatory response were to be a marker of an appropriate response to injury, then individuals exhibiting such a response would be predisposed to survive. We tested this hypothesis in swine subjected to various experimental paradigms of T/HS. Twenty-three anesthetized pigs were subjected to T/HS (12 HS-only and 11 HS + Thoracotomy; mean arterial pressure of 30 mmHg for 45–90 min) along with surgery-only controls. Plasma obtained at pre-surgery, baseline post-surgery, beginning of HS, and every 15 min thereafter until 75 min (in the HS only group) or 90 min (in the HS + Thoracotomy group) was assayed for TNF-α, IL-6, IL-10, and NO₂ ^-/NO₃ ^-. Mean post-surgery±HS TNF-α levels were significantly higher in the survivors vs. non-survivors, while non-survivors exhibited no measurable change in TNF-α levels over the same interval.

Conclusions/Significance

Contrary to the current dogma, survival in the setting of severe, acute T/HS appears to be associated with an immediate increase in serum TNF-α. It is currently unclear if this response was the cause of this protection, a marker of survival, or both. This abstract won a Young Investigator Travel Award at the SHOCK 2008 meeting in Cologne, Germany.     

Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient

Background

Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells.

Methods and Findings

A boy with ataxia telangiectasia (AT) was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient''s peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA) typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors.

Conclusions

This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.     

Accurate Path Integration in Continuous Attractor Network Models of Grid Cells

Grid cells in the rat entorhinal cortex display strikingly regular firing responses to the animal''s position in 2-D space and have been hypothesized to form the neural substrate for dead-reckoning. However, errors accumulate rapidly when velocity inputs are integrated in existing models of grid cell activity. To produce grid-cell-like responses, these models would require frequent resets triggered by external sensory cues. Such inadequacies, shared by various models, cast doubt on the dead-reckoning potential of the grid cell system. Here we focus on the question of accurate path integration, specifically in continuous attractor models of grid cell activity. We show, in contrast to previous models, that continuous attractor models can generate regular triangular grid responses, based on inputs that encode only the rat''s velocity and heading direction. We consider the role of the network boundary in the integration performance of the network and show that both periodic and aperiodic networks are capable of accurate path integration, despite important differences in their attractor manifolds. We quantify the rate at which errors in the velocity integration accumulate as a function of network size and intrinsic noise within the network. With a plausible range of parameters and the inclusion of spike variability, our model networks can accurately integrate velocity inputs over a maximum of ∼10–100 meters and ∼1–10 minutes. These findings form a proof-of-concept that continuous attractor dynamics may underlie velocity integration in the dorsolateral medial entorhinal cortex. The simulations also generate pertinent upper bounds on the accuracy of integration that may be achieved by continuous attractor dynamics in the grid cell network. We suggest experiments to test the continuous attractor model and differentiate it from models in which single cells establish their responses independently of each other.     

Body size in the Eurasian lynx in Sweden: dependence on prey availability

The Eurasian lynx (Lynx lynx) is a common predator of both roe deer (Capreolus capreolus) and reindeer (Rangifer tarandus) in Sweden. We investigated the influence of prey availability, latitude, sex, and age on body size and body mass variation of the Eurasian lynx in Sweden, using data from 243 specimens whose locality of capture, year of capture, sex, and age were known. We found that both body size and body mass of the lynx in Sweden are mainly affected by the lynx sex and age but also by the availability of prey during the first year of life. Body size and body mass of lynx as well as the density of roe deer increased from Central Sweden to South. Furthermore, body size and body mass of lynx increased from Central Sweden to North (i.e. within the reindeer husbandry area). Lynx body size was slightly smaller within the reindeer husbandry area (approximately north of latitudes 62°–63°N) compared to outside, probably because reindeer are more difficult prey to hunt, as well as being migratory and thus an unpredictable prey for the Eurasian lynx compared to the non-migratory roe deer. Our results support a growing body of evidence showing that food availability at growth has a major effect on body size of animals.     

Effect of AMF application on growth, productivity and susceptibility to Verticillium wilt of olives grown under desert conditions

The effect of arbuscular mycorrhizal fungi (AMF) on olive (Olea europaea) growth and development was followed for 4 years after transplanting in irrigated commercial orchards under arid conditions. Sites I and II were irrigated with saline water (EC?=?4.5 dS/m). In site I, the soil was infested with Verticillium dahliae and olive varieties ‘Picual’ (Verticillium susceptible) and ‘Barnea’ (relatively Verticillium tolerant) were tested. In site II, the soil was virgin soil (previously non-cultivated soil) and olive varieties ‘Souri’ and ‘Barnea’ were tested. Plants for all sites were inoculated in the nursery with Glomus intraradices alone or in a mixture with G. mosseae. Relative to non-inoculated trees, AMF colonization enhanced vegetative growth, expressed as tree height and trunk circumference, at all sites. At first commercial harvest, AMF-treated trees had higher fruit and oil yields than non-mycorrhitic controls. Under saline water irrigation, differences between inoculated and non-inoculated treatments were reduced in the slow-growing ‘Souri’ but remained apparent in the modern fast-growing ‘Barnea’. AMF colonization did not appear to improve tolerance of either ‘Picual’ or ‘Barnea’ to V. dahliae, and both were more susceptible than the non-inoculated controls. Thus inoculation of olive plants with AMF improves transplant growth and adaptation in arid areas during the first 3 years of growth and until the first commercial harvesting season.     

Therapeutic antibodies: Discovery and development using the ProteOn XPR36 biosensor interaction array system

Therapeutic monoclonal antibodies are becoming a significant and rapidly growing class of therapeutic pharmaceuticals. Their discovery and development requires fast and high-throughput methodologies for screening and selecting appropriate candidate antibodies having high affinity for the target as well as high specificity and low cross-reactivity. This study demonstrates the use of the ProteOn XPR36 protein interaction array system and its novel approach, termed One-Shot Kinetics, for the rapid screening and selection of high-affinity antibodies. This approach allows multiple quantitative protein binding analyses in parallel, providing association, dissociation, and affinity constants for several antibodies or supernatants simultaneously in one experiment. We show that the ProteOn XPR36 system is a valuable tool for use across multiple stages of the therapeutic antibody discovery and development process, enabling efficient and rapid screening after panning, affinity maturation, assay validation, and clone selection.     

Permanent Occlusion of Feeding Arteries and Draining Veins in Solid Mouse Tumors by Vascular Targeted Photodynamic Therapy (VTP) with Tookad

Background

Antiangiogenic and anti-vascular therapies present intriguing alternatives to cancer therapy. However, despite promising preclinical results and significant delays in tumor progression, none have demonstrated long-term curative features to date. Here, we show that a single treatment session of Tookad-based vascular targeted photodynamic therapy (VTP) promotes permanent arrest of tumor blood supply by rapid occlusion of the tumor feeding arteries (FA) and draining veins (DV), leading to tumor necrosis and eradication within 24–48 h.

Methodology/Principal Findings

A mouse earlobe MADB106 tumor model was subjected to Tookad-VTP and monitored by three complementary, non-invasive online imaging techniques: Fluorescent intravital microscopy, Dynamic Light Scattering Imaging and photosensitized MRI. Tookad-VTP led to prompt tumor FA vasodilatation (a mean volume increase of 70%) with a transient increase (60%) in blood-flow rate. Rapid vasoconstriction, simultaneous blood clotting, vessel permeabilization and a sharp decline in the flow rates then followed, culminating in FA occlusion at 63.2 sec±1.5SEM. This blockage was deemed irreversible after 10 minutes of VTP treatment. A decrease in DV blood flow was demonstrated, with a slight lag from FA response, accompanied by frequent changes in flow direction before reaching a complete standstill. In contrast, neighboring, healthy tissue vessels of similar sizes remained intact and functional after Tookad-VTP.

Conclusion/Significance

Tookad-VTP selectively targets the tumor feeding and draining vessels. To the best of our knowledge, this is the first mono-therapeutic modality that primarily aims at the larger tumor vessels and leads to high cure rates, both in the preclinical and clinical arenas.