Effects of human activities on Komodo dragons in Komodo National Park

Understanding how threatened wildlife can coexist with humans over the long term is a central issue in conservation and wildlife management. Komodo National Park in Eastern Indonesia, harbors the largest extant populations of the endemic Komodo dragon (Varanus komodoensis). Consistent with global trends, this species is expected to be increasingly exposed to human activities and in particular growing ecotourism activities. Here we comprehensively evaluated how human activities affected individual and population level attributes of Komodo dragons. We compared Komodo dragons phenotypic (behaviour, body size, and body condition) and demographic (age structure, sex ratio, survival, and density) responses to variation in human activities across national park. Komodo dragons were found to exhibit pronounced responses to high human activity level relative to sites with low and negligible human activities. Komodo dragons exposed to ecotourism exhibited significantly less wariness, larger body mass, better body condition, and higher survival. These results are entirely consistent with ecotourism activities that provided Komodo dragons with long-term and substantial nutritional subsidies as a consequence of feeding and human food refuse. However, we also noted the potential negative consequences of altered behaviour and adult-biased populations in ecotourism areas which may influence demographic processes through intraspecific competition or predation. To address this issue, we recommend that three management strategies to be implemented in future include: (1) removal of human-mediated nutritional subsidies, (2) alternative ecotourism, and (3) spatial regulation of ecotourism. Furthermore, we advocate the development of approaches to achieve a socio–ecological sustainability that benefits both people and wildlife conservation.     

A simple and accurate rule-based modeling framework for simulation of autocrine/paracrine stimulation of glioblastoma cell motility and proliferation by L1CAM in 2-D culture

Background

Glioblastoma multiforme (GBM) is a devastating brain cancer for which there is no known cure. Its malignancy is due to rapid cell division along with high motility and invasiveness of cells into the brain tissue. Simple 2-dimensional laboratory assays (e.g., a scratch assay) commonly are used to measure the effects of various experimental perturbations, such as treatment with chemical inhibitors. Several mathematical models have been developed to aid the understanding of the motile behavior and proliferation of GBM cells. However, many are mathematically complicated, look at multiple interdependent phenomena, and/or use modeling software not freely available to the research community. These attributes make the adoption of models and simulations of even simple 2-dimensional cell behavior an uncommon practice by cancer cell biologists.

Results

Herein, we developed an accurate, yet simple, rule-based modeling framework to describe the in vitro behavior of GBM cells that are stimulated by the L1CAM protein using freely available NetLogo software. In our model L1CAM is released by cells to act through two cell surface receptors and a point of signaling convergence to increase cell motility and proliferation. A simple graphical interface is provided so that changes can be made easily to several parameters controlling cell behavior, and behavior of the cells is viewed both pictorially and with dedicated graphs. We fully describe the hierarchical rule-based modeling framework, show simulation results under several settings, describe the accuracy compared to experimental data, and discuss the potential usefulness for predicting future experimental outcomes and for use as a teaching tool for cell biology students.

Conclusions

It is concluded that this simple modeling framework and its simulations accurately reflect much of the GBM cell motility behavior observed experimentally in vitro in the laboratory. Our framework can be modified easily to suit the needs of investigators interested in other similar intrinsic or extrinsic stimuli that influence cancer or other cell behavior. This modeling framework of a commonly used experimental motility assay (scratch assay) should be useful to both researchers of cell motility and students in a cell biology teaching laboratory.

     

Economic valuation of kelp forests in northern Chile: values of goods and services of the ecosystem

Kelp beds, besides being one of the most important benthic resources in northern Chile, provide a variety of environmental goods and services. In order to evaluate economically the wild kelp populations in northern Chile (26° to 32° S) more than simply their commercial value as a source of raw materials for alginate extraction, we used several economic indicators to holistically assess the value of a group of brown seaweeds of economic importance, Lessonia spp. and Macrocystis pyrifera: (1) market value of biomass as a source of raw material for extraction of alginic acid, (2) market value of associated species of economic importance, (3) value as a source of scientific information, (4) value as a climate buffer (CO₂ capture and release of O₂), (5) value of associated biodiversity (non-commercial species), (6) value as cultural heritage and (7) value as a reservoir of biodiversity. Existence values of kelp beds which estimate the willingness of citizens to pay and work without payment to preserve the ecosystem were calculated using the contingent valuation technique. The results indicate that kelp beds in northern Chile have a total value of US $540 million. Of this total, kelp fishery accounts for 75 % and associated-species fisheries account for 15 %. In this context, the economic value of Chilean kelp beds is mainly associated with the industry of alginate extraction. By contrast, existence value as a source of scientific information or environmental buffer for CO₂ capture or O₂ production represents only 9 % of the total value, representing a very low relative importance to society. The economic valuation of coastal resources and marine ecosystems is a complementary tool for decision making and implementation of public policies related to the conservation and sustainable exploitation of renewable resources and their ecosystems.     

Soluble L1CAM promotes breast cancer cell adhesion and migration <Emphasis Type=Italic>in vitro</Emphasis>, but not invasion

Background  

Neural recognition molecule L1CAM, which is a key protein involved in early nervous system development, is known to be abnormally expressed and shed in several types of cancers where it participates in metastasis and progression. The distinction of L1CAM presence in cancerous vs. normal tissues has suggested it to be a new target for cancer treatment. Our current study focused on the potential role of soluble L1CAM in breast cancer cell adhesion to extracellular matrix proteins, migration, and invasion.     

Distribution, seasonal use, and predation of incubation mounds of Orange-footed Scrubfowl on Komodo Island, Indonesia

ABSTRACT.   Megapodes are unique in using only heat from the environment, rather than body heat, to incubate their eggs as well as the precocious independence of their chicks on hatching. Of 22 recognized species of megapodes, 9 are listed as threatened due to factors including habitat loss and fragmentation, and predation on eggs and chicks. Orange-footed Scrubfowl ( Megapodius reinwardt ) are conspicuous components of the Oriental/Austral avifauna that inhabit the monsoon forests of the Lesser Sunda chain of islands in Indonesia. We examined the abundance, patterns of distribution, physical characteristics, seasonal activity, and predation risk of incubation mounds of Orange-footed Scrubfowl on Komodo Island in eastern Indonesia. We surveyed 13 valleys on Komodo Island from April 2002 to January 2005 and located 113 tended and 107 untended incubation mounds. Densities of scrubfowl mounds in our study were similar to that reported by investigators during the 1970s, suggesting little change in the scrubfowl population since then. Most scrubfowl mounds were on sandy or loamy soils in open monsoon forest with little overhead shade, and placement of mounds in such areas may ensure adequate temperatures for egg incubation. Although some mounds were tended during all months, mound use peaked during the late wet season in March. During the dry season (April–November), only a few mounds were tended. Komodo dragons ( Varanus komodoensis ) and wild pigs ( Sus scrofa ) were the primary predators of scrubfowl eggs, with no indication of egg predation by humans. The valley with the largest number of untended mounds in our study also had the largest number of active Komodo dragon nests. This suggests an effect of Komodo dragons on scrubfowl numbers, but additional study is needed.     

Automated time-lapse microscopy and high-resolution tracking of cell migration

We describe a novel fully automated high-throughput time-lapse microscopy system and evaluate its performance for precisely tracking the motility of several glioma and osteoblastic cell lines. Use of this system revealed cell motility behavior not discernable with conventional techniques by collecting data (1) from closely spaced time points (minutes), (2) over long periods (hours to days), (3) from multiple areas of interest, (4) in parallel under several different experimental conditions. Quantitation of true individual and average cell velocity and path length was obtained with high spatial and temporal resolution in “scratch” or “wound healing” assays. This revealed unique motility dynamics of drug-treated and adhesion molecule-transfected cells and, thus, this is a considerable improvement over current methods of measurement and analysis. Several fluorescent vital labeling methods commonly used for end-point analyses (GFP expression, DiO lipophilic dye, and Qtracker nanocrystals) were found to be useful for time-lapse studies under specific conditions that are described. To illustrate one application, fluorescently labeled tumor cells were seeded onto cell monolayers expressing ectopic adhesion molecules, and this resulted in consistently reduced tumor cell migration velocities. These highly quantitative time-lapse analysis methods will promote the creation of new cell motility assays and increase the resolution and accuracy of existing assays.Joseph S. Fotos and Vivek P. Patel contributed equally to this work     

A study of replacement of timolol-pilocarpine with latanoprost in pseudoexfoliation glaucoma

The aim of the study was to evaluate the efficacy of replacing current dual local therapy (timolol and pilocarpine) with latanoprost 0.005% in 71 pseudoexfoliation glaucoma patients with controlled intraocular pressure (IOP). 39 patients switched to latanoprost 0.005%) and 32 patients continued timolol-pilocarpine therapy. Mean diurnal (IOP) was measured at baseline, after 0.5, 1, 3 and 6 months of treatment. After 6 months 38 patients with latanoprost and 30 patients with timolol-pilocarpine had completed the study. At baseline the mean diurnal IOP was 20.4 +/- 2.0 mmHg for patients in latanoprost treatment group and 21.4 +/- 2.1 mmHg for patients in timolol-pilocarpine group. At the end of the study, after 6 months of treatment, the mean diurnal IOP values were 16.6 +/- 2.4 and 17.9 +/- 2.0 mmHg respectively. IOP was statistically significantly reduced from baseline (p < 0.001). The mean diurnal IOP change from baseline was -3.3 +/- 0.5 mmHg (mean +/- SEM, ANCOVA) for the patients treated with latanoprost and -3.2 +/- 0.4 mmHg for the patients treated with timolol + pilocarpine. This difference in IOP reduction between groups was not statistically significant (z = 0.69; p = 0.49). This study showed that combination therapy (timolol plus pilocarpine) in pseudoexfoliation glaucoma can effectively be replaced by latanoprost monotherapy.     

Evidence for the early emergence of piperaquine-resistant Plasmodium falciparum malaria and modeling strategies to mitigate resistance

Multidrug-resistant Plasmodium falciparum parasites have emerged in Cambodia and neighboring countries in Southeast Asia, compromising the efficacy of first-line antimalarial combinations. Dihydroartemisinin + piperaquine (PPQ) treatment failure rates have risen to as high as 50% in some areas in this region. For PPQ, resistance is driven primarily by a series of mutant alleles of the P. falciparum chloroquine resistance transporter (PfCRT). PPQ resistance was reported in China three decades earlier, but the molecular driver remained unknown. Herein, we identify a PPQ-resistant pfcrt allele (China C) from Yunnan Province, China, whose genotypic lineage is distinct from the PPQ-resistant pfcrt alleles currently observed in Cambodia. Combining gene editing and competitive growth assays, we report that PfCRT China C confers moderate PPQ resistance while re-sensitizing parasites to chloroquine (CQ) and incurring a fitness cost that manifests as a reduced rate of parasite growth. PPQ transport assays using purified PfCRT isoforms, combined with molecular dynamics simulations, highlight differences in drug transport kinetics and in this transporter’s central cavity conformation between China C and the current Southeast Asian PPQ-resistant isoforms. We also report a novel computational model that incorporates empirically determined fitness landscapes at varying drug concentrations, combined with antimalarial susceptibility profiles, mutation rates, and drug pharmacokinetics. Our simulations with PPQ-resistant or -sensitive parasite lines predict that a three-day regimen of PPQ combined with CQ can effectively clear infections and prevent the evolution of PfCRT variants. This work suggests that including CQ in combination therapies could be effective in suppressing the evolution of PfCRT-mediated multidrug resistance in regions where PPQ has lost efficacy.