Restoration Ecology: Two-Sex Dynamics and Cost Minimization

We model a spatially detailed, two-sex population dynamics, to study the cost of ecological restoration. We assume that cost is proportional to the number of individuals introduced into a large habitat. We treat dispersal as homogeneous diffusion. The local population dynamics depends on sex ratio at birth, and allows mortality rates to differ between sexes. Furthermore, local density dependence induces a strong Allee effect, implying that the initial population must be sufficiently large to avert rapid extinction. We address three different initial spatial distributions for the introduced individuals; for each we minimize the associated cost, constrained by the requirement that the species must be restored throughout the habitat. First, we consider spatially inhomogeneous, unstable stationary solutions of the model's equations as plausible candidates for small restoration cost. Second, we use numerical simulations to find the smallest cluster size, enclosing a spatially homogeneous population density, that minimizes the cost of assured restoration. Finally, by employing simulated annealing, we minimize restoration cost among all possible initial spatial distributions of females and males. For biased sex ratios, or for a significant between-sex difference in mortality, we find that sex-specific spatial distributions minimize the cost. But as long as the sex ratio maximizes the local equilibrium density for given mortality rates, a common homogeneous distribution for both sexes that spans a critical distance yields a similarly low cost

Peptide-chelating agent conjugate for selective targeting of somatostatin receptor type1: Synthesis and characterization

Previously reported results suggest that the analogue of the somatostatin des-AA 1,2,5[D-Trp 8,IAmp 9]-somatostatin (CH-275) peptide bearing chelating agents able to coordinate radioactive metals could be used for scintigraphic imaging of tumor lesions overexpressing sstr1. An efficient synthetic procedure for the preparation of the somatostatin analogue CH-275 and its conjugate DTPAGlu-Gly-CH-275, bearing the chelating agent DTPAGlu (DTPAGlu = N,N-bis[2-[bis(carboxy-ethyl)amino]ethyl]-L-glutamic acid) on the N-terminus, by solid-phase peptide synthesis and 9-flourenymethyoxycarbonyl (Fmoc) chemistry, is here reported. Rapid and efficient labeling of DTPAGlu-Gly-CH-275 was achieved by addition of IIIIn(III) to the compound. Typical yields were greater than 97% as determined by reversed phase high performance liquid chromatography (HPLC) at specific activities in the range 4-9 GBq/μmol (100-250 Ci/mmol). A preliminary biological assay of the binding ability of IIIIn-DTPAGlu-Gly-CH-275 indicates, however, that the labeled compound does not display any specific interaction with somatostatin sstrl receptors in the tested cell lines. To confirm this unexpected negative result, competition binding experiments were carried out, in which fixed tracer amounts of the 125!-labeled somatostatin-14 were incubated with the receptor-expressing cells in the presence of DTPAGlu-Gly-CH-275 or CH-275 at concentrations ranging from 10 -10 to 10 -3 M. While CH-275 shows a IC 50 of 80 nM similar to that already found in displacement experiments on CHO-Kl sstrl-transfected cells, DTPAGlu-Gly-CH-275 displays instead very low or negligible affinity towards this receptor. The NMR solution characterization indicates that the presence of DTPAGlu does not influence the conformational and chemical features of the peptide moiety, thus suggesting that the loss in binding activity should be due to steric hindrance of either the chelating agent DTPAGlu or its indium comple

In vitro and in vivo evaluation of In-111-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging

Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging and therapy. Receptors of the cholecystokinin family have been shown to be overexpressed in different types of neuroendocrine tumors. The purposes of this study were to evaluate the cholecystokinin octapeptide amide (CCK8) peptide tagged with a diethylenetriaminepentaacetic acid derivative (DTPAGlu) and to test whether a 111In-labeled conjugate (111In-DTPAGlu-G-CCK8, a derivative containing the chelating agent DTPAGlu bound through a glycine linker at the N-terminal end of the bioactive peptide CCK8) is suitable for cholecystokinin-B receptor (CCKBR) imaging. Methods: CCK8 was synthesized by solidphase techniques and covalently coupled to DTPAGlu through a glycine linker at its amino terminus. The compound was labeled with 111In. The radiochemical purity and stability of the compound were assessed by chromatographic methods. NIH-3T3 and A431 cells overexpressing CCKBR were used to characterize the in vitro properties of the compound. Nude mice bearing control and CCKBR-overexpressing A431 xenografts were used as an in vivo model. Results: DTPAGlu-G-CCK8 showed rapid and efficient labeling with 111In. The radiolabeled conjugate showed specific binding to both cell lines overexpressing CCKBR. Binding was saturable, with a dissociation constant of 20 nmol/L in both cell systems. Both cell lines showed internalization of the ligand after interaction with the receptor. Biodistribution studies showed rapid localization of 111In-DTPAGlu- G-CCK8 on CCKBR-overexpressing A431 xenografts that was severalfold higher than that on control tumors at all time points tested. Unbound activity showed rapid clearance of over 80% through the kidneys by 30 min after injection. The labeled peptide conjugate was very stable in serum but showed a rapid breakdown after injection. Incubation with kidney homogenates suggested that most breakdown occurred in the kidneys, favoring the clearance of unbound activity. Conclusion: Our findings indicate that the in vitro and in vivo characteristics of 111In-DTPAGlu-G-CCK8 are favorable for CCKBR imaging, as thepeptide shows high-affinity binding to the receptor, is internalized in CCKBR-expressing cells, and shows avid uptake in CCKBR-overexpressing xenografts, with rapid clearance of unbound radioactivity through the kidneys. Furthermore, the ease of synthesis, high labeling efficiency, and chemical stability of DTPAGlu make this chelating moiety an ideal candidate for widespread use in peptide radiolabeling for nuclear medicine applications

Monitoring the correction of glycogen storage disease type 1a in a mouse model using [18F]FDG and a dedicated animal scanner

Monitoring gene therapy of glycogen storage disease type 1a in a mouse model was achieved using [18F]FDG and a dedicated animal scanner. The G6Pase knockout (KO) mice were compared to the same mice after infusion with a recombinant adenovirus containing the murine G6Pase gene (Ad-mG6Pase). Serial images of the same mouse before and after therapy were obtained and compared with wild-type (WT) mice of the same strain to determine the uptake and retention of [18F]FDG in the liver. Image data were acquired from heart, blood pool and liver for twenty minutes after injection of [18F]FDG. The retention of [18F]FDG was lower for the WT mice compared to the KO mice. The mice treated with adenovirus-mediated gene therapy had retention similar to that found in age-matched WT mice. These studies show that FDG can be used to monitor the G6Pase concentration in liver of WT mice as compared to G6Pase KO mice. In these mice, gene therapy returned the liver function to that found in age matched WT controls as measured by the FDG kinetics in the liver compared to that found in age matched wild type controlsPublicad

Metabolic state alters economic decision making under risk in humans

Background: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity

The changing landscape : ecosystem responses to urbanization and pollution across climatic and societal gradients

Author Posting. © Ecological Society of America, 2008. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Frontiers in Ecology and the Environment 6 (2008): 264–272, doi:10.1890/070147.Urbanization, an important driver of climate change and pollution, alters both biotic and abiotic ecosystem properties within, surrounding, and even at great distances from urban areas. As a result, research challenges and environmental problems must be tackled at local, regional, and global scales. Ecosystem responses to land change are complex and interacting, occurring on all spatial and temporal scales as a consequence of connectivity of resources, energy, and information among social, physical, and biological systems. We propose six hypotheses about local to continental effects of urbanization and pollution, and an operational research approach to test them. This approach focuses on analysis of “megapolitan” areas that have emerged across North America, but also includes diverse wildland-to-urban gradients and spatially continuous coverage of land change. Concerted and coordinated monitoring of land change and accompanying ecosystem responses, coupled with simulation models, will permit robust forecasts of how land change and human settlement patterns will alter ecosystem services and resource utilization across the North American continent. This, in turn, can be applied globally.We thank the NSF LTER program for its support

Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

Background. Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease. Methods. A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16CDKN2A, BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16CDKN2A genes. Results. For melanoma susceptibility, investigations at germline level indicated that p16CDKN2A was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16CDKN2A gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16CDKN2A silencing). Conclusion. Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis

Control of primary productivity and the significance of photosynthetic bacteria in a meromictic kettle lake.

During 1986 planktonic primary production and controlling factors were investigated in a small (A0 = 11.8 · 103 m2, Zmax = 11.5 m) meromictic kettle lake (Mittlerer Buchensee). Annual phytoplankton productivity was estimated to ca 120 gC · m–2 · a–1 (1,42 tC · lake–1 · a–1). The marked thermal stratification of the lake led to irregular vertical distributions of chlorophylla concentrations (Chla) and, to a minor extent, of photosynthesis (Az). Between the depths of 0 to 6 m low Chla concentrations (< 7 mg · m–3) and comparatively high background light attenuation (kw = 0,525 m–1, 77% of total attenuation due to gelbstoff and abioseston) was found. As a consequence, light absorption by algae was low (mean value 17,4%) and self-shading was absent. Because of the small seasonal variation of Chla concentrations, no significant correlation between Chla and areal photosynthesis (A) was observed. Only in early summer (June–July) biomass appears to influence the vertical distribution of photosynthesis on a bigger scale. Around 8 m depth, low-light adapted algae and phototrophic bacteria formed dense layers. Due to low ambient irradiances, the contribution of these organisms to total primary productivity was small. Primary production and incident irradiance were significantly correlated with each other (r2 = 0.68). Although the maximum assimilation number (Popt) showed a clear dependence upon water temperature (Q10 = 2.31), the latter was of minor importance to areal photosynthesis

Timing of sentinel node biopsy independently predicts disease-free and overall survival in clinical stage I-II melanoma patients: A multicentre study of the Italian Melanoma Intergroup (IMI)

Background: Sentinel lymph node biopsy (SNB) still remains a key procedure to appropriately stage melanoma patients and to select those who are candidate to novel treatments with immunotherapy and targeted therapy in the adjuvant setting. The impact of timing of SNB on disease-free survival (DFS) and overall survival (OS) is still unclear. Material and methods: The study was conducted at 6 Italian Melanoma Intergroup (IMI) centres and included 8953 consecutive clinical stage I-II melanoma patients who were diagnosed, treated, and followed up between November 1997 and March 2018. All patients were prospectively included in dedicated IMI database. Multivariable Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to DFS and OS. Results: Considering the whole population, at multivariable analysis, after adjusting for age, gender, Breslow thickness, site, ulceration, and the SNB status, a delay in the timing of SNB was associated with a better DFS (adjusted hazard ratio [aHR, delayed versus early SNB] 0.98, 95% confidence interval [CI] 0.97\u20130.99, p < 0.001) and OS (aHR 0.98, 95% CI 0.97\u20130.99, p = 0.001). Specifically, in patients with a negative SNB status, a beneficial impact of delayed SNB (i.e. at least 32 days after primary excision) was confirmed for DFS (aHR 0.70, 95%CI 0.63\u20130.79, p < 0.001) and OS (aHR 0.69, 95%CI 0.61\u20130.78, p < 0.001), whereas in those with a positive SNB status, DFS (aHR 0.96, 95%CI 0.84\u20131.09, p = 0.534) and OS (aHR 0.94 95%CI 0.81\u20131.08, p = 0.374) were not significantly different in patients with early or delayed SNB. Conclusions: Our study does not support a strict time interval for SNB. These results may be useful for national guidelines, for counselling patients and reducing the number of high urgency referrals

Ecological Invasion, Roughened Fronts, and a Competitor's Extreme Advance: Integrating Stochastic Spatial-Growth Models

Both community ecology and conservation biology seek further understanding of factors governing the advance of an invasive species. We model biological invasion as an individual-based, stochastic process on a two-dimensional landscape. An ecologically superior invader and a resident species compete for space preemptively. Our general model includes the basic contact process and a variant of the Eden model as special cases. We employ the concept of a "roughened" front to quantify effects of discreteness and stochasticity on invasion; we emphasize the probability distribution of the front-runner's relative position. That is, we analyze the location of the most advanced invader as the extreme deviation about the front's mean position. We find that a class of models with different assumptions about neighborhood interactions exhibit universal characteristics. That is, key features of the invasion dynamics span a class of models, independently of locally detailed demographic rules. Our results integrate theories of invasive spatial growth and generate novel hypotheses linking habitat or landscape size (length of the invading front) to invasion velocity, and to the relative position of the most advanced invader.Comment: The original publication is available at www.springerlink.com/content/8528v8563r7u2742