The influence of dietary carbohydrate and fat on kidney calcification and the urinary excretion of N-acetyl-beta-glucosaminidase (EC 3.2.1.30).

1. Male Sprague-Dawley rats were fed on diets containing either sucrose or starch as the carbohydrate component. In one experiment, the diets also contained 200 g either butter or polyunsaturated margarine/kg; in a second experiment, the diets contained less fat in the form of 20 g maize oil/kg. 2. Over a period of 11 months assays were made in the urine of several ions and of the activity of the enzyme N-acetyl-β-glucosaminidase (β-2-acetamido-2-deoxy-β-D glucoside acetamidodeoxygluco-hydrolase; EC 3.2.1.30); at 13 months, examination was made of some of the abdominal viscera, especially of the kidneys. 3. In rats fed on the higher amount of fat, dietary sucrose produced a higher activity of the enzyme than did dietary starch, and a greater excretion of inorganic phosphate. 4. With both the higher and lower amounts of dietary fat, sucrose led to an increase in the weight of the liver and of the kidneys, and an increase in the concentration of calcium and of phosphate in kidney tissue. With the higher amount of fat, sucrose also produced an increase in the concentration of magnesium in the kidney. There was no difference in the concentration of any of the ions assayed in the plasma or, apart from inorganic phosphate, in the urine. 5. The kidneys of the sucrose-fed rats showed nephrocalcinosis, mostly in the cortico-medullary region, and basophilic deposits in the tubules. Attention is drawn to this unusual occurrence of nephrocalcinosis in male rats

Age dependence of serum beta-N-acetylhexosaminidase (NAG) activity

Serum Nacetyl-beta-Dglucosaminidase (NAG; EC 3.2.1.30) is a hexosaminidase and may be a predictor of vascular injury, e.g., in infant respiratory distress syndrome, pneumonia, bronchopulmonary dysplasia and necrotizing enterocolitis. To estimate the new diagnostic prospects we have modified our urinary NAG assay. In this sensitive colorimetric microassay, VRAGlcNAc was used as a substrate. In the present study the age dependence of serum NAG activity was investigated in newborn babies, infants (124 months), children (218 years) and adults (1980 years). Serum NAG activity was found to be agedependent; it is higher in early childhood (1159 U/l) but decreases to a constant value at the age of 12 years. After the age of 2 years it is similar to adults NAG (1030 U/l). In pediatrics agematched reference ranges must be taken into consideration

The Organizational Account of Function is an Etiological Account of Function

The debate on the notion of function has been historically dominated by dispositional and etiological accounts, but recently a third contender has gained prominence: the organizational account. This original theory of function is intended to offer an alternative account based on the notion of self-maintaining system. However, there is a set of cases where organizational accounts seem to generate counterintuitive results. These cases involve cross-generational traits, that is, traits that do not contribute in any relevant way to the self-maintenance of the organism carrying them, but instead have very important effects on organisms that belong to the next generation. We argue that any plausible solution to the problem of cross-generational traits shows that the organizational account just is a version of the etiological theory and, furthermore, that it does not provide any substantive advantage over standard etiological theories of function

A simple mathematical model of gradual Darwinian evolution: Emergence of a Gaussian trait distribution in adaptation along a fitness gradient

We consider a simple mathematical model of gradual Darwinian evolution in continuous time and continuous trait space, due to intraspecific competition for common resource in an asexually reproducing population in constant environment, while far from evolutionary stable equilibrium. The model admits exact analytical solution. In particular, Gaussian distribution of the trait emerges from generic initial conditions.Comment: 21 pages, 2 figures, as accepted to J Math Biol 2013/03/1

The influence of liver dysfunction on cyclosporine pharmacokinetics -A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs-

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects. © 1989 The Japan Surgical Society

Long Term Implications of Climate Change on Crop Planning

The effects of climate change have been much speculated on in the past few years. Consequently, there has been intense interest in one of its key issues of food security into the future. This is particularly so given population increase, urban encroachment on arable land, and the degradation of the land itself. Recently, work has been done on predicting precipitation and temperature for the next few decades as well as developing optimisation models for crop planning. Combining these together, this paper examines the effects of climate change on a large food producing region in Australia, the Murrumbidgee Irrigation Area. For time periods between 1991 and 2071 for dry, average and wet years, an analysis is made about the way that crop mixes will need to change to adapt for the effects of climate change. It is found that sustainable crop choices will change into the future, and that large-scale irrigated agriculture may become unviable in the region in all but the wettest years

Species Differentiation on a Dynamic Landscape: Shifts in Metapopulation Genetic Structure Using the Chronology of the Hawaiian Archipelago

Species formation during adaptive radiation often occurs in the context of a changing environment. The establishment and arrangement of populations, in space and time, sets up ecological and genetic processes that dictate the rate and pattern of differentiation. Here, we focus on how a dynamic habitat can affect genetic structure, and ultimately, differentiation among populations. We make use of the chronology and geographical history provided by the Hawaiian archipelago to examine the initial stages of population establishment and genetic divergence. We use data from a set of 6 spider lineages that differ in habitat affinities, some preferring low elevation habitats with a longer history of connection, others being more specialized for high elevation and/or wet forest, some with more general habitat affinities. We show that habitat preferences associated with lineages are important in ecological and genetic structuring. Lineages that have more restricted habitat preferences are subject to repeated episodes of isolation and fragmentation as a result of lava flows and vegetation succession. The initial dynamic set up by the landscape translates over time into discrete lineages. Further work is needed to understand how genetic changes interact with a changing set of ecological interactions amongst a shifting mosaic of landscapes to achieve species formation

Filter-based stochastic algorithm for global optimization

We propose the general Filter-based Stochastic Algorithm (FbSA) for the global optimization of nonconvex and nonsmooth constrained problems. Under certain conditions on the probability distributions that generate the sample points, almost sure convergence is proved. In order to optimize problems with computationally expensive black-box objective functions, we develop the FbSA-RBF algorithm based on the general FbSA and assisted by Radial Basis Function (RBF) surrogate models to approximate the objective function. At each iteration, the resulting algorithm constructs/updates a surrogate model of the objective function and generates trial points using a dynamic coordinate search strategy similar to the one used in the Dynamically Dimensioned Search method. To identify a promising best trial point, a non-dominance concept based on the values of the surrogate model and the constraint violation at the trial points is used. Theoretical results concerning the sufficient conditions for the almost surely convergence of the algorithm are presented. Preliminary numerical experiments show that the FbSA-RBF is competitive when compared with other known methods in the literature.The authors are grateful to the anonymous referees for their fruitful comments and suggestions.The first and second authors were partially supported by Brazilian Funds through CAPES andCNPq by Grants PDSE 99999.009400/2014-01 and 309303/2017-6. The research of the thirdand fourth authors were partially financed by Portuguese Funds through FCT (Fundação para Ciência e Tecnologia) within the Projects UIDB/00013/2020 and UIDP/00013/2020 of CMAT-UM and UIDB/00319/2020

Comparison of breast and bowel cancer screening uptake patterns in a common cohort of South Asian women in England

Background: Inequalities in uptake of cancer screening by ethnic minority populations are well documented in a number of international studies. However, most studies to date have explored screening uptake for a single cancer only. This paper compares breast and bowel cancer screening uptake for a cohort of South Asian women invited to undertake both, and similarly investigates these women's breast cancer screening behaviour over a period of fifteen years. Methods: Screening data for rounds 1, 2 and 5 (1989-2004) of the NHS breast cancer screening programme and for round 1 of the NHS bowel screening pilot (2000-2002) were obtained for women aged 50-69 resident in the English bowel screening pilot site, Coventry and Warwickshire, who had been invited to undertake breast and bowel cancer screening in the period 2000-2002. Breast and bowel cancer screening uptake levels were calculated and compared using the chi-squared test. Results: 72,566 women were invited to breast and bowel cancer screening after exclusions. Of these, 3,539 were South Asian and 69,027 non-Asian; 18,730 had been invited to mammography over the previous fifteen years (rounds 1 to 5). South Asian women were significantly less likely to undertake both breast and bowel cancer screening; 29.9% (n = 1,057) compared to 59.4% (n = 40,969) for non-Asians (p < 0.001). Women in both groups who consistently chose to undertake breast cancer screening in rounds 1, 2 and 5 were more likely to complete round 1 bowel cancer screening. However, the likelihood of completion of bowel cancer screening was still significantly lower for South Asians; 49.5% vs. 82.3% for non-Asians, p < 0.001. South Asian women who undertook breast cancer screening in only one round were no more likely to complete bowel cancer screening than those who decided against breast cancer screening in all three rounds. In contrast, similar women in the non-Asian population had an increased likelihood of completing the new bowel cancer screening test. The likelihood of continued uptake of mammography after undertaking screening in round 1 differed between South Asian religio-linguistic groups. Noticeably, women in the Muslim population were less likely to continue to participate in mammography than those in other South Asian groups. Conclusions: Culturally appropriate targeted interventions are required to reduce observed disparities in cancer screening uptakes

Bistability in Apoptosis by Receptor Clustering

Apoptosis is a highly regulated cell death mechanism involved in many physiological processes. A key component of extrinsically activated apoptosis is the death receptor Fas, which, on binding to its cognate ligand FasL, oligomerize to form the death-inducing signaling complex. Motivated by recent experimental data, we propose a mathematical model of death ligand-receptor dynamics where FasL acts as a clustering agent for Fas, which form locally stable signaling platforms through proximity-induced receptor interactions. Significantly, the model exhibits hysteresis, providing an upstream mechanism for bistability and robustness. At low receptor concentrations, the bistability is contingent on the trimerism of FasL. Moreover, irreversible bistability, representing a committed cell death decision, emerges at high concentrations, which may be achieved through receptor pre-association or localization onto membrane lipid rafts. Thus, our model provides a novel theory for these observed biological phenomena within the unified context of bistability. Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our model also suggests a mechanism by which cells may function as bistable life/death switches independently of any such dynamics in their downstream components. Our results highlight the role of death receptors in deciding cell fate and add to the signal processing capabilities attributed to receptor clustering.Comment: Accepted by PLoS Comput Bio