Modelling individual plant growth at a variable mean density or at a specific spatial setting

Neighbouring plants generally compete for the limiting resources in order to grow and reproduce. Some resources, e.g., sun light, may be monopolised by the larger plants and this may lead to asymmetric competition where a plant, which is twice as large, grows more than twice as fast. A previously published individual-based Richards growth model that describes the asymmetric growth of individual plants is here generalised with respect to a variable mean plant density and an explicit spatial setting.     

Sleep deprivation in a quantitative physiologically based model of the ascending arousal system

A physiologically based quantitative model of the human ascending arousal system is used to study sleep deprivation after being calibrated on a small set of experimentally based criteria. The model includes the sleep-wake switch of mutual inhibition between nuclei which use monoaminergic neuromodulators, and the ventrolateral preoptic area. The system is driven by the circadian rhythm and sleep homeostasis. We use a small number of experimentally derived criteria to calibrate the model for sleep deprivation, then investigate model predictions for other experiments, demonstrating the scope of application. Calibration gives an improved parameter set, in which the form of the homeostatic drive is better constrained, and its weighting relative to the circadian drive is increased. Within the newly constrained parameter ranges, the model predicts repayment of sleep debt consistent with experiment in both quantity and distribution, asymptoting to a maximum repayment for very long deprivations. Recovery is found to depend on circadian phase, and the model predicts that it is most efficient to recover during normal sleeping phases of the circadian cycle, in terms of the amount of recovery sleep required. The form of the homeostatic drive suggests that periods of wake during recovery from sleep deprivation are phases of relative recovery, in the sense that the homeostatic drive continues to converge toward baseline levels. This undermines the concept of sleep debt, and is in agreement with experimentally restricted recovery protocols. Finally, we compare our model to the two-process model, and demonstrate the power of physiologically based modeling by correctly predicting sleep latency times following deprivation from experimental data.     

Linking individual response to biotic interactions with community structure: a trait-based framework

1.  Due to species-specificity of the outcomes of biotic interactions, it is difficult to generalize from observed biotic interactions at the individual plant level to the effect of those interactions at the community level. To evaluate the importance of biotic interactions in shaping plant communities, it is necessary to understand how the outcomes of the complex interactions observed at the individual level can influence community structure.
2.  Here, we propose a trait-based framework that identifies and organises mechanisms affecting community structure (here described with relative abundances of plant functional traits – i.e. the distribution of trait values at the community level). We applied our approach to a single leaf trait, specific leaf area (SLA), to link individual responses to plant interactions with community structure (SLA distribution observed at the community level) and to test whether biotic interactions can predict the functional composition of subalpine grasslands. We evaluated the generality of our model through a cross-validation with a set of eight subalpine grasslands independent from the four fields used to build the model.
3.  We found that competition and facilitation were able to explain the functional composition of subalpine grasslands, and the relevant fitness components (survival or growth) explaining this link changed depending on the limiting resources. When soil water availability was limiting, positive plant-plant interactions acting on survival were able to explain community structure. In contrast, when no water limitation was observed competition acting on individual growth was the main driver of community structure.
4.  Our framework enables evaluation of the consequences of biotic interactions observed at individual level on community structure, thereby indicating when and where different types of plant-plant interactions are important.     

Somatic mutagenesis with a Sleeping Beauty transposon system leads to solid tumor formation in zebrafish

Large-scale sequencing of human cancer genomes and mouse transposon-induced tumors has identified a vast number of genes mutated in different cancers. One of the outstanding challenges in this field is to determine which genes, when mutated, contribute to cellular transformation and tumor progression. To identify new and conserved genes that drive tumorigenesis we have developed a novel cancer model in a distantly related vertebrate species, the zebrafish, Danio rerio. The Sleeping Beauty (SB) T2/Onc transposon system was adapted for somatic mutagenesis in zebrafish. The carp ß-actin promoter was cloned into T2/Onc to create T2/OncZ. Two transgenic zebrafish lines that contain large concatemers of T2/OncZ were isolated by injection of linear DNA into the zebrafish embryo. The T2/OncZ transposons were mobilized throughout the zebrafish genome from the transgene array by injecting SB11 transposase RNA at the 1-cell stage. Alternatively, the T2/OncZ zebrafish were crossed to a transgenic line that constitutively expresses SB11 transposase. T2/OncZ transposon integration sites were cloned by ligation-mediated PCR and sequenced on a Genome Analyzer II. Between 700–6800 unique integration events in individual fish were mapped to the zebrafish genome. The data show that introduction of transposase by transgene expression or RNA injection results in an even distribution of transposon re-integration events across the zebrafish genome. SB11 mRNA injection resulted in neoplasms in 10% of adult fish at ∼10 months of age. T2/OncZ-induced zebrafish tumors contain many mutated genes in common with human and mouse cancer genes. These analyses validate our mutagenesis approach and provide additional support for the involvement of these genes in human cancers. The zebrafish T2/OncZ cancer model will be useful for identifying novel and conserved genetic drivers of human cancers.     

Modelling developmental instability in relation to individual fitness: a fully Bayesian latent variable model approach

Since the influential paper by Palmer and Strobeck in 1986, the statistical analysis of fluctuating asymmetry and developmental stability has received much attention. Most studies deal with one of the following four difficulties: (i) correcting for bias in asymmetry estimates due to measurement error; (ii) quantifying sampling error in the estimation of individual developmental stability using individual asymmetry; (iii) the detection of directional asymmetry and antisymmetry; and (iv) combining data from several traits. Yet, few studies have focused on statistical properties of estimating a relationship between individual developmental stability and other factors (e.g. fitness). In this paper I introduce a fully Bayesian model in which the unobservable individual developmental stability is treated as a latent variable. The latter is then related to individual fitness. I show by means of the analysis of simulated data that this approach has several advantages over traditional techniques. First, the method provides unbiased (but slightly less accurate) estimates of slopes between developmental stability and fitness taking all sources of error into account. Secondly, it allows proper investigation of non‐linear associations. Finally, the model allows unbiased estimation of unobserved fitness of individuals that have been measured on left and right side.     

Modelling the mating system of polar bears: a mechanistic approach to the Allee effect

Allee effects may render exploited animal populations extinction prone, but empirical data are often lacking to describe the circumstances leading to an Allee effect. Arbitrary assumptions regarding Allee effects could lead to erroneous management decisions so that predictive modelling approaches are needed that identify the circumstances leading to an Allee effect before such a scenario occurs. We present a predictive approach of Allee effects for polar bears where low population densities, an unpredictable habitat and harvest-depleted male populations result in infrequent mating encounters. We develop a mechanistic model for the polar bear mating system that predicts the proportion of fertilized females at the end of the mating season given population density and operational sex ratio. The model is parametrized using pairing data from Lancaster Sound, Canada, and describes the observed pairing dynamics well. Female mating success is shown to be a nonlinear function of the operational sex ratio, so that a sudden and rapid reproductive collapse could occur if males are severely depleted. The operational sex ratio where an Allee effect is expected is dependent on population density. We focus on the prediction of Allee effects in polar bears but our approach is also applicable to other species.     

Overcompensation and grazing optimisation in a swan–pondweed system?

1. The general notion is that negative effects of vertebrate herbivores on water plants, which play a key role in freshwaters, prevail, and that positive feedbacks of herbivores on plants are insignificant. 2. The most likely systems to find such positive feedbacks are those in which herbivores exert strong feeding pressures on plants during part of the year. Previous theoretical work has suggested that compensatory production occurs when migratory Bewick's swans forage on tubers of fennel pondweed. As a corollary, the swans can exploit the tubers down to a level that maximises their tuber yield. 3. In order to test these hypotheses, I measured pondweed tuber biomass on three occasions per year (just before and after foraging, and just before tuber sprouting) in three consecutive years. The 17 sampling sites in the Lauwersmeer (the Netherlands) were classified according to their silt content and water depth. Within four silt‐depth classes, I predicted for each year tuber biomass production and, from that, the optimum foraging threshold that would result in the maximum tuber biomass yield. 4. Water depth did not affect tuber production, and silt content only did in one of the 3 years. In accordance with overcompensation predictions, tuber production was higher at plots with moderate foraging pressures than at plots with little or no grazing. However, the winter and summer conditions following the swan foraging had large unpredictable effects on tuber mortality and production. 5. These results indicate that overcompensation by fennel pondweed occurs and that Bewick's swans are generally able to profit from it, albeit without fine‐tuning of the foraging threshold to the yield.     

Predator decline leads to decreased stability in a coastal fish community

Fisheries exploitation has caused widespread declines in marine predators. Theory predicts that predator depletion will destabilise lower trophic levels, making natural communities more vulnerable to environmental perturbations. However, empirical evidence has been limited. Using a community matrix model, we empirically assessed trends in the stability of a multispecies coastal fish community over the course of predator depletion. Three indices of community stability (resistance, resilience and reactivity) revealed significantly decreasing stability concurrent with declining predator abundance. The trophically downgraded community exhibited weaker top‐down control, leading to predator‐release processes in lower trophic levels and increased susceptibility to perturbation. At the community level, our results suggest that high predator abundance acts as a stabilising force to the naturally stochastic and highly autocorrelated dynamics in low trophic species. These findings have important implications for the conservation and management of predators in marine ecosystems and provide empirical support for the theory of predatory control.     

Long-term exposure to chromium(VI) oxide leads to defects in sulfate transport system in chinese hamster ovary cells

Chromium(VI) resistant Chinese hamster ovary (CHO) cell lines were established in this study by exposing parental CHO-K1 cells to sequential increases in CrO₃ concentration. The final concentration of CrO₃ used for selection was 7 μM for Cr7 and 16 μM for Cr16 cells. Cr16-1 was a subclone derived from Cr16 cells. Next, these resistant cells were cultured in media without CrO₃ for more than 6 months. The resistance of these cells to CrO₃ was determined by colony-forming ability following a 24-h treatment. The LD₅₀ of CrO₃ for chromium(VI) resistant cells was at least 25-fold higher than that of the parental cells. The cellular growth rate, chromosome number, and the hprt mutation frequency of these chromium(VI) resistant cells were quite similar to their parental cells. The glutathione level, glutathione S-transferase, catalase activity, and metallothionine mRNA level in Cr7 and Cr16-1 cells were not significantly different from their parental cells. Furthermore, Cr16-1 cells were as sensitive as CHO-K1 cells to free-radical generating agents, including hydrogen peroxide, nickel chloride, and methanesulfonate methyl ester, and emetine, i.e., a protein synthesis inhibitor. The uptake of chromium(VI) and the remaining amount of this metal in these resistant and the parental cell lines were assayed by atomic absorption spectrophotometry. Experimental results indicated that a vastly smaller amount of CrO₃ entered the resistant cell lines than their parental cells did. A comparison was made of the sulfate uptake abilities of CHO-K1 and chromium(VI) resistant cell lines. These results revealed that the uptake of sulfate anion was substantially reduced in Cr7 and Cr16-1 cells. Extracellular chloride reduced sulfate uptake in CHO-K1 but not in Cr16-1 cells. Therefore, the major causative for chromium(VI) resistance in these resistant cells could possibly be due to the defects in SO₄^2-/C1^? transport system for uptake chromium(VI).     

Altered ubiquitin-proteasome system leads to neuronal cell death in a spontaneous obese rat model

Background

Obesity is associated with various progressive age-related diseases, including neurological disorders. However, underlying molecular basis for increased risk of neurodegeneration in obesity is unknown. A suitable animal model would immensely help in understanding the obesity-linked neurological problems.

Methods

A spontaneously developed obese rat (WNIN/Ob) which is highly vulnerable for a variety of degenerative diseases was isolated from the existing WNIN stock rats. Ultrastructure of neurons in the cerebral cortex of 12-month old obese rats was evaluated by transmission electron microscopy. qRT-PCR and immunoblotting of ubiquitin C-terminal hydrolases (UCHs), ubiquitin, proteasomal sub-units, markers of ER stress and apoptosis were performed in the cerebral cortex. Proteasome activity was assayed by fluorometric method. Immunohistochemistry was performed for mediators of apoptosis, which was further confirmed by TUNEL assay. These investigations were also carried in high-fat diet-induced obese rat model.

Results

Neurons in the cerebral cortex of 12-month obese rats showed swollen mitochondria, disrupted ER and degenerating axons, nucleus and finally neurons. Results showed altered UPS, existence of ER stress, up-regulation of apoptotic markers and apoptosis in the cerebral cortex of obese rats. It appears that UCHL-1 mediated apoptosis through stabilizing p53 might play a role in neuronal cell death in obese rat. Similar changes were observed in the brain of diet-induced obese WNIN rats.

Conclusion

Altered UPS could be one of the underlying mechanisms for the neuronal cell death in obese conditions.

General significance

This is the first report to highlight the role of altered UPS in neurodegeneration due to obesity.     

Transition from a random to an ideal free to an ideal despotic distribution: the effect of individual difference in growth

Individual differences in growth can lead to a monopolistic form of food competition. We studied the long-term transition in the mode of competition and the distribution of individuals between food patches of the cloned salmonid fish, Oncorhynchus masou ishikawae, in the laboratory. This transition was accompanied by growth depensation, i.e., the increase over time in the variance of size between individuals resulting from the differences in individual growth rates. The 120-cm experimental tanks were divided into two compartments (patches) between which an opaque partition was placed. Fish were able to move freely between the patches and therefore were able to assess the patch quality using long-term memory, but they were not able to see the food input in the other patch directly. The distribution between the two food patches, the amount of food gained, and the growth and the agonistic behavior of four groups of six individuals were observed over 4 weeks. We found that (1) within-group variation in body weight increased with time; (2) on average, the better patch was used by more individuals than predicted by a random distribution but fewer individuals than predicted by an ideal free distribution, and (3) the distribution and pattern of resource use by the fish changed over the 4-week experimental period from a random distribution to an ideal free distribution and finally to an ideal despotic distribution. We suggest that growth depensation causes the long-term change in the spatial distribution and pattern of resource use by competitors. Received: December 19, 2000 / Accepted: March 19, 2001     

Interaction with Ppil3 leads to the cytoplasmic localization of Apoptin in tumor cells

Apoptin, a small protein encoded by chicken anemia virus (CAV), induces cell death specifically in cancer cells. In normal cells, Apoptin remains in the cytoplasm; whereas in cancerous cells, it migrates into the nucleus and kills the cell. Cellular localization appears to be crucial. Through a yeast two-hybrid screen, we identified human Peptidyl-prolyl isomerase-like 3 (Ppil3) as one of the Apoptin-associated proteins. Ppil3 could bind Apoptin directly, and held Apoptin in cytoplasm even in tumor cells. We then demonstrated that the nuclearcytoplasmic distribution of Apoptin is related to the expression level of intrinsic Ppil3. Moreover, extrinsic modifying of Ppil3 levels also resulted in nuclearcytoplasmic shuffling of Apoptin. The Apoptin P109A mutant, located between the putative nuclear localization and export signals, could significantly impair the function of Ppil3. Our results suggest a new direction for the localization mechanism study of Apoptin in cells.     

Ventricular flow dynamics with varying LVAD inflow cannula lengths: In-silico evaluation in a multiscale model

Left ventricular assist devices are associated with thromboembolic events, which are potentially caused by altered intraventricular flow. Due to patient variability, differences in apical wall thickness affects cannula insertion lengths, potentially promoting unfavourable intraventricular flow patterns which are thought to be correlated to the risk of thrombosis. This study aimed to present a 3D multiscale computational fluid dynamic model of the left ventricle (LV) developed using a commercial software, Ansys, and evaluate the risk of thrombosis with varying inflow cannula insertion lengths in a severely dilated LV. Based on a HeartWare HVAD inflow cannula, insertion lengths of 5, 19, 24 and 50 mm represented cases of apical hypertrophy, typical ranges of apical thicknesses and an experimental length, respectively. The risk of thrombosis was evaluated based on blood washout, residence time, instantaneous blood stagnation and a pulsatility index. By introducing fresh blood to displace pre-existing blood in the LV, after 5 cardiac cycles, 46.7%, 45.7%, 45.1% and 41.8% of pre-existing blood remained for insertion lengths of 5, 19, 24 and 50 mm, respectively. Compared to the 50 mm insertion, blood residence time was at least 9%, 7% and 6% higher with the 5, 19 and 24 mm insertion lengths, respectively. No instantaneous stagnation at the apex was observed directly after the E-wave. Pulsatility indices adjacent to the cannula increased with shorter insertion lengths. For the specific scenario studied, a longer insertion length, relative to LV size, may be advantageous to minimise thrombosis by increasing LV washout and reducing blood residence time.     

Modelling vertical transmission in vector-borne diseases with applications to Rift Valley fever

We present two ordinary differential equation models for Rift Valley fever (RVF) transmission in cattle and mosquitoes. We extend existing models for vector-borne diseases to include an asymptomatic host class and vertical transmission in vectors. We define the basic reproductive number, ₀, and analyse the existence and stability of equilibrium points. We compute sensitivity indices of ₀ and a reactivity index (that measures epidemicity) to parameters for baseline wet and dry season values. ₀ is most sensitive to the mosquito biting and death rates. The reactivity index is most sensitive to the mosquito biting rate and the infectivity of hosts to vectors. Numerical simulations show that even with low equilibrium prevalence, increases in mosquito densities through higher rainfall, in the presence of vertical transmission, can result in large epidemics. This suggests that vertical transmission is an important factor in the size and persistence of RVF epidemics.     

Immunization with heat shock protein 105-pulsed dendritic cells leads to tumor rejection in mice

Recently, we reported that heat shock protein 105 (HSP105) DNA vaccination induced anti-tumor immunity. In this study, we set up a preclinical study to investigate the usefulness of dendritic cells (DCs) pulsed with mouse HSP105 as a whole protein for cancer immunotherapy in vivo. The recombinant HSP105 did not induce DC maturation, and the mice vaccinated with HSP105-pulsed BM-DCs were markedly prevented from the growth of subcutaneous tumors, accompanied with a massive infiltration of both CD4+ T cells and CD8+ T cells into the tumors. In depletion experiments, we proved that both CD4+ T cells and CD8+ T cells play a crucial role in anti-tumor immunity. Both CD4+ T cells and CD8+ T cells specific to HSP105 were induced by stimulation with HSP105-pulsed DCs. As a result, vaccination of mice with BM-DCs pulsed with HSP105 itself could elicit a stronger tumor rejection in comparison to DNA vaccination.     

Excessive rainfall leads to maize yield loss of a comparable magnitude to extreme drought in the United States

Increasing drought and extreme rainfall are major threats to maize production in the United States. However, compared to drought impact, the impact of excessive rainfall on crop yield remains unresolved. Here, we present observational evidence from crop yield and insurance data that excessive rainfall can reduce maize yield up to ?34% (?17 ± 3% on average) in the United States relative to the expected yield from the long‐term trend, comparable to the up to ?37% loss by extreme drought (?32 ± 2% on average) from 1981 to 2016. Drought consistently decreases maize yield due to water deficiency and concurrent heat, with greater yield loss for rainfed maize in wetter areas. Excessive rainfall can have either negative or positive impact on crop yield, and its sign varies regionally. Excessive rainfall decreases maize yield significantly in cooler areas in conjunction with poorly drained soils, and such yield loss gets exacerbated under the condition of high preseason soil water storage. Current process‐based crop models cannot capture the yield loss from excessive rainfall and overestimate yield under wet conditions. Our results highlight the need for improved understanding and modeling of the excessive rainfall impact on crop yield.     

Treatment with alpha-difluoromethylornithine plus a spermidine analog leads to spermine depletion and growth inhibition in cultured L1210 leukemia cells

Of the three biological polyamines, putrescine (Put), spermidine (Spd), and spermine (Spm), the relevance of Spm to cell proliferation has yet to be defined because of our general inability to deplete it selectively in intact cells. In the present study, Spm depletion was accomplished by treating cultured L1210 cells for 96 hr with alpha-difluoromethylornithine (DFMO) and an analog of Spd such as aminopropylcadaverine, N4-methylSpd, N4-ethylSpd, or homoSpd. DFMO, a specific inhibitor of ornithine decarboxylase, halts continued polyamine biosynthesis and the Spd analog serves as a functional substitute for Spd. Thus, while the Spd analog fulfills the role(s) of Spd in cell proliferation, Spm becomes steadily depleted. In cells treated with DFMO plus the analog, aminopropylcadaverine, Spm pools decline steadily and growth inhibition occus after 48 hr (when Spm pools decline to 60% of control). By 96 hr, Spm is approximately 15% of control and growth is less than 30%. Prevention studies with exogenous polyamines confirm a causal relationship between Spm depletion and growth inhibition. The critical levels of polyamines for cell proliferation to take place were found to be 30% of control for Spd and 60% for Spm. The use of DFMO plus a Spd analog is proposed as a system for studying the cellular consequences of Spm depletion. Spd depletion can be achieved for comparison purposes by treating cells with DFMO alone.     

Ultraviolet-A irradiation but not ultraviolet-B or infrared-A irradiation leads to a disturbed zinc homeostasis in cells

Changes of the redox balance in cells alter the availability of intracellular free Zn(2+). Here, cells were exposed to ultraviolet (UV)-A, UV-B, or infrared (IR)-A light irradiation, and the intracellular free zinc pool was monitored. Under sublethal conditions only UV-A irradiation resulted in a transient cytoplasmic and nuclear increase of intracellular free Zn(2+). Likewise, tert-butyl hydroperoxide and singlet oxygen, but not H(2)O(2) or intracellular generation of O(2)(*-) by redox cyclers, mimicked the effects of UV-A irradiation, while disulfide stress by diamide only led to a transient cytoplasmic zinc release. These results show that only certain types of subtoxic cellular stress massively disturb the zinc homeostasis in cells.