Redistribution of nitrogen in an ecosystem due to long-term fertilization and continuous cropping

Summary When a leguminous crop like cowpea was included in a crop rotation of Ganga 5 maize, CO 7 ragi and CO 2 cowpea, the total nitrogen content in the soil was considerably increased even in the unfertilized plots. The leguminous crop fixed atmospheric nitrogen at the rate of 205 kg N/hectare/year. Potassium did not influence the status whereas phosphorus, over a background of N, improved it. Considerable quantity of N fixed was observed to have been redistributed in the soil which depended on the fertilization pattern.     

Coupling biomechanics to a cellular level model: an approach to patient-specific image driven multi-scale and multi-physics tumor simulation

Modeling of tumor growth has been performed according to various approaches addressing different biocomplexity levels and spatiotemporal scales. Mathematical treatments range from partial differential equation based diffusion models to rule-based cellular level simulators, aiming at both improving our quantitative understanding of the underlying biological processes and, in the mid- and long term, constructing reliable multi-scale predictive platforms to support patient-individualized treatment planning and optimization. The aim of this paper is to establish a multi-scale and multi-physics approach to tumor modeling taking into account both the cellular and the macroscopic mechanical level. Therefore, an already developed biomodel of clinical tumor growth and response to treatment is self-consistently coupled with a biomechanical model. Results are presented for the free growth case of the imageable component of an initially point-like glioblastoma multiforme tumor. The composite model leads to significant tumor shape corrections that are achieved through the utilization of environmental pressure information and the application of biomechanical principles. Using the ratio of smallest to largest moment of inertia of the tumor material to quantify the effect of our coupled approach, we have found a tumor shape correction of 20% by coupling biomechanics to the cellular simulator as compared to a cellular simulation without preferred growth directions. We conclude that the integration of the two models provides additional morphological insight into realistic tumor growth behavior. Therefore, it might be used for the development of an advanced oncosimulator focusing on tumor types for which morphology plays an important role in surgical and/or radio-therapeutic treatment planning.     

Stemwood volume increment changes in European forests due to climate change—a simulation study with the EFISCEN model

This paper presents the results of a modelling study of future net annual increment changes in stemwood of European forests owing to climate change. Seven process‐based growth models were applied to 14 representative forest sites across Europe under one climate change scenario. The chosen scenario was the HadCM2 run, based on emission scenario IS92a, and resulted in an increase in mean temperature of 2.5 °C between 1990 and 2050, and an increase in annual precipitation of 5–15%. The information from those runs was incorporated in a transient way in a large‐scale forest resource scenario model, EFISCEN (European forest information scenario). European scale forest resource projections were made for 28 countries covering 131.7 million ha of forest under two management scenarios for the period until 2050. The results showed that net annual increments in stemwood of European forests under climate change will further increase with an additional 0.9 m³ ha^?1 y^?1 in 2030 compared to the ongoing increase under a current climate scenario, i.e. an extra 18% increase. After 2030 the extra increment increase is reduced to 0.79 m³ ha^?1 y^?1 in 2050. Under climate change, absolute net annual increments will increase from the present 4.95, on average for Europe, to 5.93 m³ ha^?1 y^?1 in 2025. After 2025, increments in all scenarios start to decline owing to ageing of the forest and the high growing stocks being reached. The results of the present study are surrounded by large uncertainties. These uncertainties are caused by unknown emissions in the future, unknown extent of climate change, uncertainty in process‐based models, uncertainty in inventory data, and uncertainty in inventory projection. Although the results are thus not conclusive, climate change may lead to extra felling opportunities in European forests of 87 million m³y^?1. Because Europe's forests are intensively managed already, management may adapt to climate change relatively easily. However, this study also indicates that climate change may lead to a faster build‐up of growing stocks. That may create a less stable forest resource in terms of risks to storm damage.     

Assessing non-specificity of resistance in wheat to head blight caused by inoculation with European strains of Fusarium culmorum,F. graminearum and F. nivale using a multiplicative model for interaction

To determine whether resistance to Fusarium head blight in winter wheat is horizontal and non-species specific, 25 genotypes from five European countries were tested at six locations across Europe in the years 1990, 1991, and 1992. The five genotypes from each country had to cover the range from resistant to susceptible. The locations involved were Wageningen, Vienna, Rennes, Hohenheim, Oberer Lindenhof, and Szeged. In total, 17 local strains of Fusarium culmorum, F. graminearum, and F. nivale were used for experimental inoculation. One strain, F. culmorum IPO 39-01, was used at all locations. Best linear unbiased predictions (BLUPs) for the head blight ratings of the genotypes were formed within each particular location for each combination of year and strain. The BLUPs over all locations were collected in a genotype-by environment table in which the genotypic dimension consisted of the 25 genotypes, while the environmental dimension was made up of 59 year-by-strain-by-location combinations. A multiplicative model was fitted to the genotype by-environment interaction in this table. The inverses of the variances of the genotype-by-environment BLUPs were used as weights. Interactions between genotypes and environments were written as sums of products between genotypic scores and environmental scores. After correction for year-by-location influence very little variation in environmental scores could be ascribed to differences between strains. This provided the basis for the conclusion that the resistance to Fusarium head blight in winter wheat was of the horizontal and non-species specific type. There was no indication for any geographical pattern in virulence genes. Any reasonable aggressive strain, a F. culmorum strain for the cool climates and a F. graminearum strain for the warmer humid areas, should be satisfactory for screening purposes.     

Economic impact of clinical mastitis in a dairy herd assessed by stochastic simulation using different methods to model yield losses

The main aim of the present study was to examine the economic consequences of a reduction in the incidence of clinical mastitis (CM) at herd level under current Swedish farming conditions. A second objective was to ask whether the estimated cost of CM alters depending upon whether the model reflects the fact that in different stages of lactation, CM gives rise to different yield-loss patterns or postulates just one type of yield-loss pattern irrespective of when, during lactation, CM occurs. A dynamic and stochastic simulation model, SimHerd, was used to study the effects of CM in a herd with 150 cows (9000 kg of energy-corrected milk per cow-year). Four herd types, defined by production level and reproductive performance, were modelled to investigate possible interactions between herd type and response to a reduction in the risk of CM. Technical and economic results, given the initial incidence of CM (25.6 per 100 cow-years), were studied together with the consequences of reducing the initial risk of CM by 50% and 90% throughout lactation and the consequences of reducing the initial risk by 50% and 90% before peak yield. A conventional way of modelling yield losses - i.e. one employing a single yield-loss pattern irrespective of when, during the lactation period, the cow develops CM - was compared with a new modelling strategy in which CM was assumed to affect production differently depending on its lactational timing. The effect of the choice of reference level when estimating yield losses was investigated by comparing the results obtained using the potential yield of mastitic cows, had they not developed CM, with those obtained using the yield of non-mastitic cows. The yearly maximum avoidable cost of CM at herd level was estimated at €14 504, corresponding to 6.9% of the net return given the initial incidence of CM. Expressed per cow-year, the maximum avoidable cost was €97. The cost per case of CM was estimated at €428. Herd types all responded in a similar manner to the reduced relative risk of CM. There were no major differences in the results obtained using the new and the conventional modelling strategy, with the exception of the cost per case of CM. Similarities between the results obtained using the two methods were particularly evident when the mastitic cows' own yield level, had they not developed CM, was used as the reference for production in healthy cows when yield losses were estimated. It was concluded that the conventional way of modelling yield losses is adequate and should, for the foreseeable future, be used in decision support systems.     

Loss of animal seed dispersal increases extinction risk in a tropical tree species due to pervasive negative density dependence across life stages

Overhunting in tropical forests reduces populations of vertebrate seed dispersers. If reduced seed dispersal has a negative impact on tree population viability, overhunting could lead to altered forest structure and dynamics, including decreased biodiversity. However, empirical data showing decreased animal-dispersed tree abundance in overhunted forests contradict demographic models which predict minimal sensitivity of tree population growth rate to early life stages. One resolution to this discrepancy is that seed dispersal determines spatial aggregation, which could have demographic consequences for all life stages. We tested the impact of dispersal loss on population viability of a tropical tree species, Miliusa horsfieldii, currently dispersed by an intact community of large mammals in a Thai forest. We evaluated the effect of spatial aggregation for all tree life stages, from seeds to adult trees, and constructed simulation models to compare population viability with and without animal-mediated seed dispersal. In simulated populations, disperser loss increased spatial aggregation by fourfold, leading to increased negative density dependence across the life cycle and a 10-fold increase in the probability of extinction. Given that the majority of tree species in tropical forests are animal-dispersed, overhunting will potentially result in forests that are fundamentally different from those existing now.     

Evaluation of a two‐part regression calibration to adjust for dietary exposure measurement error in the Cox proportional hazards model: A simulation study

Dietary questionnaires are prone to measurement error, which bias the perceived association between dietary intake and risk of disease. Short‐term measurements are required to adjust for the bias in the association. For foods that are not consumed daily, the short‐term measurements are often characterized by excess zeroes. Via a simulation study, the performance of a two‐part calibration model that was developed for a single‐replicate study design was assessed by mimicking leafy vegetable intake reports from the multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) study. In part I of the fitted two‐part calibration model, a logistic distribution was assumed; in part II, a gamma distribution was assumed. The model was assessed with respect to the magnitude of the correlation between the consumption probability and the consumed amount (hereafter, cross‐part correlation), the number and form of covariates in the calibration model, the percentage of zero response values, and the magnitude of the measurement error in the dietary intake. From the simulation study results, transforming the dietary variable in the regression calibration to an appropriate scale was found to be the most important factor for the model performance. Reducing the number of covariates in the model could be beneficial, but was not critical in large‐sample studies. The performance was remarkably robust when fitting a one‐part rather than a two‐part model. The model performance was minimally affected by the cross‐part correlation.     

Assessing the ecological health risk in a conserved mangrove ecosystem due to heavy metal pollution: A case study from Sundarbans Biosphere Reserve,India

Sundarbans Biosphere Reserve (SBR) is the world's largest contiguous conserved mangrove forest with unique flora and fauna, but it still has to bear the brunt of anthropogenic disturbances due to huge population pressure. This study aimed to identify the sources, extent of metal pollution (Cd, Cr, Mn, Ni, Pb, and Zn), and their potential ecological risk in this fragile ecosystem. Sediments were collected from 10 locations with varied levels of anthropogenic pressure from the fringe of the reserve forest. Cluster analysis (CA) and factor analysis (FA) identified Ni, Cd, and Pb as the major anthropogenic pollutants in this area. Concentrations of Pb (27.79–47.07 mg/kg) and Cd (0.8–3.3 mg/kg) were found to be higher in areas reliant on fossil fuel-operated motorboats for transport and dependent on rechargeable batteries to cope with the shortage of electricity. The contamination factor (C_f), geoaccumulation index (I_geo), and ecological risk index (ERI) highlight that populated areas are mostly exposed to Cd, Pb, and Cr contamination. Interpolation maps identified that the central part of the area is acutely affected by Cd pollution, whereas the main ecotourism routes within the reserve forest have high Pb concentrations. This study concludes that conservation-friendly ecotourism and improper disposal of batteries can also pose a threat to this ecosystem and these possibilities could be considered during formulation of conservation plans.     

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

Genetic factors may interact with lifestyle factors to modify obesity risk. FTO and PPARG2 are relevant obesogenes. Our aim was to explore the effect of Pro12Ala (rs1801282) of PPARG2 and rs9939609 of FTO on obesity risk and to examine their interaction with lifestyle factors in an elderly population. Subjects (n = 978; aged 69 ± 6) were recruited from the SUN (Seguimiento Universidad de Navarra) Project. DNA was obtained from saliva, and lifestyle and dietary data were collected by validated self-reported questionnaires. Genotyping was assessed by RT-PCR plus allele discrimination. Subjects carrying the Ala allele of PPARG2 gene had a significantly increased obesity risk compared to non-carrier (Pro12Pro) subjects (OR, 1.66; 95  % CI, 1.01–2.74; p = 0.045). Greater obesity risk was also found in inactive or high carbohydrate intake subjects with the Ala12 allele of PPARG2 gene. Interestingly, subjects carrying the Ala allele of the PPARG2 gene and with a high CHO (>246 g/day) intake had an increased obesity risk compared to Pro12Pro subjects (OR, 2.67; 95 % CI, 1.3–5.46; p = 0.007; p for [CHO × PPARG2] interaction = 0.046). Moreover, in subjects with a high CHO intake, the co-presence of the Ala allele of PPARG2 gene and one minor A allele (rs9939609) of FTO gene did increase obesity risk (OR, 3.26; 95 % CI, 1.19–8.89; p = 0.021) when compared to non-carrier (Pro12Pro/TT) subjects. In conclusion, it appears that lifestyle factors may act as effect modifiers for obesity risk linked to Ala12 allele of the PPARG2 gene and the minor A allele of FTO gene in an elderly population.     

Combining ancestral sequence reconstruction with protein design to identify an interface hotspot in a key metabolic enzyme complex

It is important to identify hotspot residues that determine protein–protein interactions in interfaces of macromolecular complexes. We have applied a combination of ancestral sequence reconstruction and protein design to identify hotspots within imidazole glycerol phosphate synthase (ImGPS). ImGPS is a key metabolic enzyme complex, which links histidine and de novo purine biosynthesis and consists of the cyclase subunit HisF and the glutaminase subunit HisH. Initial fluorescence titration experiments showed that HisH from Zymomonas mobilis (zmHisH) binds with high affinity to the reconstructed HisF from the last universal common ancestor (LUCA‐HisF) but not to HisF from Pyrobaculum arsenaticum (paHisF), which differ by 103 residues. Subsequent titration experiments with a reconstructed evolutionary intermediate linking LUCA‐HisF and paHisF and inspection of the subunit interface of a contemporary ImGPS allowed us to narrow down the differences crucial for zmHisH binding to nine amino acids of HisF. Homology modeling and in silico mutagenesis studies suggested that at most two of these nine HisF residues are crucial for zmHisH binding. These computational results were verified by experimental site‐directed mutagenesis, which finally enabled us to pinpoint a single amino acid residue in HisF that is decisive for high‐affinity binding of zmHisH. Our work shows that the identification of protein interface hotspots can be very efficient when reconstructed proteins with different binding properties are included in the analysis. Proteins 2017; 85:312–321. © 2016 Wiley Periodicals, Inc.     

Integrating telemetry with a predictive model to assess habitat preferences and juvenile survival in an endangered freshwater turtle

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Treatment of hepatocellular carcinoma in a mouse xenograft model with an immunotoxin which is engineered to eliminate vascular leak syndrome

Vascular leak syndrome (VLS) is the major dose-limiting toxicity of immunotoxin and interleukin-2 therapy. It has been evidenced that VLS-inducing molecules share a three-amino acid consensus motif, (x)D(y), which may be responsible for initiating VLS. Here we have constructed a recombinant immunotoxin (SMFv-PE38KDEL) by genetically fusing PE38KDEL to a single-chain antibody derived from SM5-1 monoclonal antibody, which has a high specificity for melanoma, hepatocellular carcinoma and breast cancer. In order to eliminate VLS induced by this PE38KDEL-based immunotoxin, a panel of mutants were generated by changing amino acid residues adjacent to its three (x)D(y) motifs in the three-dimensional structure. One of the SMFv-PE38KDEL mutants, denoted as mut1, displayed a similar protein synthesis inhibitory in a reticulocyte lysate translation assay compared to the wild-type SMFv-PE38KDEL (wt). The in vitro cytotoxicity assay indicated that mut1 specifically killed SM5-1 binding protein-positive tumor cells, although its cytotoxicity was slightly less than wt. In contrast, mut1 was shown to be much weaker in inducing VLS in mice than wt. The LD₅₀ values of wt and mut1 in mice were investigated with the result that the LD₅₀ of mut1 was about tenfold higher than that of wt. The in vivo antitumor activity of wt and mut1 were also compared in tumor-bearing nude mice. Both wt and mut1 were effective in inhibiting the tumor growth but mut1 showed improved therapeutic efficacy. These studies suggest mut1 may be a novel PE-based immunotoxin with much less toxicity for clinical use. Hao Wang, Shuichuan Song and Geng Kou contributed equally to this paper.     

Dominant role of local dipolar interactions in phosphate binding to a receptor cleft with an electronegative charge surface: equilibrium, kinetic, and crystallographic studies.

Stringent specificity and complementarity between the receptor, a periplasmic phosphate-binding protein (PBP) with a two-domain structure, and the completely buried and dehydrated phosphate are achieved by hydrogen bonding or dipolar interactions. We recently found that the surface charge potential of the cleft between the two domains that contains the anion binding site is intensely electronegative. This novel finding prompted the study reported here of the effect of ionic strength on the equilibrium and rapid kinetics of phosphate binding. To facilitate this study, Ala197, located on the edge of the cleft, was replaced by a Trp residue (A197W PBP) to generate a fluorescence reporter group. The A197W PBP-phosphate complex retains wild-type Kd and X-ray structure beyond the replacement residue. The Kd (0.18 microM) at no salt is increased by 20-fold at greater than 0.30 M NaCl. Stopped-flow fluorescence kinetic studies indicate a two-step binding process: (1) The phosphate (L) binds, at near diffusion-controlled rate, to the open cleft form (Po) of PBP to produce an intermediate, PoL. This rate decreases with increasing ionic strength. (2) The intermediate isomerizes to the closed-conformation form, PcL. The results indicate that the high specificity, affinity, and rate of phosphate binding are not influenced by the noncomplementary electronegative surface potential of the cleft. That binding depends almost entirely on local dipolar interactions with the receptor has important ramification in electrostatic interactions in protein structures and in ligand recognition.     

Immunocytochemical identification of neural elements in the central nervous systems of a snail,some insects,a fish,and a mammal with an antiserum to the molluscan cardio-excitatory tetrapeptide FMRF-amide

Summary The choriocapillaris is the fenestrated capillary network that supplies a large portion of the nutrients required by the retinal pigment epithelium, photoreceptor cells, and other cells of the outer neural retina. The permeability of these capillaries was investigated in the rat by the use of ferritin (mol. wt. approx. 480,000; mol. diam. 110Å) as a tracer. Ninety minutes after intravascular ferritin administration, a high concentration of tracer particles was distributed uniformly in the capillary lumina but few particles were present in Bruch's membrane, the multilayered basement membrane that separates the choriocapillary endothelium from the retinal pigment epithelium. The bulk of the tracer remained in the capillary lumina with a definite blockage seen at fenestral, channel, and vesicle diaphragms. These results indicate that the rat choriocapillary endothelium, unlike the fenestrated endothelia lining other capillary beds, constitutes an important barrier to the passage of ferritin and presumably of circulating native molecules of similar size.Supported by NIH grants EY 01889 and EY 07034 from the National Eye Institute and a grant-in-aid from Fight for Sight, Inc., of New York City     

Partial monosomy 21 (q11.2→q21.3) combined with 3p25.3→pter monosomy due to an unbalanced translocation in a patient presenting dysmorphic features and developmental delay

We describe a female patient of 1 year and 5 months-old, referred for genetic evaluation due to neuropsychomotor delay, hearing impairment and dysmorphic features. The patient presents a partial chromosome 21 monosomy (q11.2→q21.3) in combination with a chromosome 3p terminal monosomy (p25.3→pter) due to an unbalanced de novo translocation. The translocation was confirmed by fluorescence in situ hybridization (FISH) and the breakpoints were mapped with high resolution array. After the combined analyses with these techniques the final karyotype was defined as 45,XX,der(3)t(3;21)(p25.3;q21.3)dn,-21.ish der(3)t(3;21)(RP11-329A2-,RP11-439F4-,RP11-95E11-,CTB-63H24 +).arr 3p26.3p25.3(35,333-10,888,738)) × 1,21q11.2q21.3(13,354,643-27,357,765) × 1. Analysis of microsatellite DNA markers pointed to a paternal origin for the chromosome rearrangement. This is the first case described with a partial proximal monosomy 21 combined with a 3p terminal monosomy due to a de novo unbalanced translocation.     

Patch-clamp studies on the anomalous mole fraction effect of the K+ channel in cytoplasmic droplets ofNitella: An attempt to distinguish between a multi-ion single-file pore and an enzyme kinetic model with lazy state

Summary Patch-clamp studies have been employed in order to check whether the assumption of a multi-ion single-file pore is necessary for the explanation of the anomalous mole fraction effect or whether this effect can also be explained by a single-barrier enzyme kinetic model. Experiments in the cell-attached configuration were done on the tonoplast membrane of cytoplasmic droplets ofNitella in solutions containing 150 mol m^–3 of K⁺ plus Tl⁺ with seven different K⁺/Tl⁺ ratios. At first sight, the results seem to support the multi-ion single-file pore, because apparent open channel conductivity displays the anomalous mole fraction effect, whereas open-probability has not been found to be dependent on the K⁺/Tl⁺ ratio. Changes in open probability would be expected for a single-barrier enzyme kinetic model with a lazy state. On the other hand, the lazy-state model is more successful in explaining the measuredI-V curves. The entire slope of the apparent open channel current-voltage curves rotates with changing K⁺/Tl⁺ ratios in the whole voltage range between –100 and + 80 mV. Numerical calculations on the basis of multi-ion single-file pores could create the anomalous mole fraction effect only in a limited voltage range with intersectingI-V curves. The apparent absence of an effect on open probability which is postulated by the lazy-state model can be explained if switching into and out of the lazy state is faster than can be resolved by the temporal resolution of 1 msec.