Effects of one-year low-dose growth hormone (GH) therapy on body composition, lipid profile and carbohydrate metabolism in young adults with childhood-onset severe GH deficiency confirmed after completion of growth promotion

Introduction: The symptoms of GH deficiency (GHD) in adults include: abnormalities in body composition, unfavourable lipid profile, early atherosclerosis and impaired quality of life. The aim of the study was the selection of patients with confirmed severe GHD from among all the children treated due to GHD, who could benefit from GH therapy continuation in adulthood and the optimization of GH dosage in young adults with severe GHD. Material and methods: The study group consisted of 54 young adults (38 male), age 17.6 +/- 1.5 years, with childhood-onset GHD, who had reached final height. At least 1 month after the GH therapy withdrawal, the second evaluation of GH secretion was performed in all the patients. In 24% of patients, permanent severe GHD (PSGHD) was confirmed, but a group of 9 patients (4 male) was involved in renewed GH therapy. Results: The renewed GH therapy gave positive effects, including a significant increase in fat-free mass and a decrease in fat mass, and a significant decrease in LDL-cholesterol, but connected with an insignificant decrease of HDL-cholesterol serum concentration and improved results of quality of life (QoL) assessment. During the therapy, an insignificant increase of fasting insulin was observed, with no change in fasting glucose and only a slight increase in HbA(1c) percentage. A decrease of insulin sensitivity was also observed, but both insulin secretion and the values of insulin resistance indices still remained within the reference range. Conclusions: The observed positive effects on body composition, lipid metabolism and QoL, together with the absence of adverse events, confirm the indications for GH therapy in young adults with severe GHD.     

Fertility assurance and breeding synchrony

Extrapair fertilizations are an important factor in reproduction of many bird species. It has been suggested that pursuit of extrapair fertilizations provides a selective pressure capable of affecting the “ecological” attributes of some bird species. It is known that in some cases the pursuit of extrapair copulations is motivated by fertility assurance. That is, there are populations in which (i) some males and females cannot produce viable offspring, and (ii) there is no pre-copulatory way to choose a compatible mate. In such situations individuals mate for “economic” reasons and attempt to secure reproduction by copulating with multiple partners. Here we formulate and analyze a simple game theoretical model addressing the interplay between environmental constraints and the pursuit of fertility assurance via extrapair copulations in determining breeding synchrony. Our results indicate that breeding synchrony in such cases is determined by the magnitude of the costs (due to environmental constraints) of breeding asynchronously versus the worth of the attendant increase in extrapair opportunities.     

Fertility assurance through extrapair fertilization,and male parental effort

Extrapair paternity (EPP) has been observed in many formally monogamous species. Male pursuit of extrapair fertilizations (EPF) is explained by the advantages of having offspring that receive essential paternal care from other males. Because females are capable of exercising a degree of control over the post-copulatory sperm competition, EPP’s persistence indicates that females benefit from EPF. Thus, EPP involves cooperation between mated females and extrapair males. On the other hand, mated males exhibit a spectrum of anti-cuckolding strategies. Hence, extrapair attributes of diverse species and populations reported in the literature are particular solutions of evolutionary games involving gender-specific cuckolding/anti-cuckolding strategies. Here we use game theoretical methods to study the effect of male paternal effort conserving strategies in situations where females seek EPF for reasons of genetic compatibility and/or in pursuit of genetic diversity for their offspring. Our results indicate that in these circumstances pursuit of EPF is the only evolutionary stable female strategy. Males, on the other hand, have two, mutually exclusive, evolutionary stable strategies: males that restrict parental care regardless of their mate’s fidelity, and males that never restrict parental care. That is, when females seek EPF for reasons of fertility assurance and/or genetic diversity, the conditional male strategy—therein the male’s parental efforts are based on his certainty of paternity—loses in competition with the unconditional strategies.     

From reciprocity to unconditional altruism through signalling benefits

Cooperation among genetically unrelated individuals is commonly explained by the potential for future reciprocity or by the risk of being punished by group members. However, unconditional altruism is more difficult to explain. We demonstrate that unconditional altruism can evolve as a costly signal of individual quality (i.e. a handicap) as a consequence of reciprocal altruism. This is because the emergent correlation between altruism and individual quality in reciprocity games can facilitate the use of altruism as a quality indicator in a much wider context, outside the reciprocity game, thus affecting its further evolution through signalling benefits. Our model, based on multitype evolutionary game theory shows that, when the additive signalling benefit of donating help exceeds the cost for only some individuals (of high-quality state) but not for others (of low-quality state), the population possesses an evolutionarily stable strategy (ESS) profile wherein high-quality individuals cooperate unconditionally while low-quality individuals defect or play tit-for-tat (TfT). Hence, as predicted by Zahavi's handicap model, signalling benefits of altruistic acts can establish a stable generosity by high-quality individuals that no longer depends on the probability of future reciprocation or punishment.     

AgNOR quantification in the diagnosis of follicular pattern thyroid lesions

OBJECTIVE: To evaluate the usefulness of silver staining of nucleolar organizer regions (AgNORs) in the preoperative diagnosis of follicular lesions in the thyroid with computer-aided morphometric analysis of the silver dots. STUDY DESIGN: Forty-eight cytologic smears of the thyroid were divided into 3 groups according to the results of postoperative histopathologic examination: hyperplastic nodules in nodular goiter (NG) (20), follicular thyroid adenoma (FTA) (20) and follicular thyroid carcinoma (FTC) (8). They were silver stained. The slides were analyzed with a computerized system for image analysis. Nearly 20 variables describing AgNORs were calculated (related to the area of the dots, number of dots and intranuclear localization of the dots). RESULTS: Only assessment of the total area of AgNORs in the nucleus allowed distinguishing between malignant and benign lesions. It was possible to determine the cutoff value of the total area of AgNORs in the nucleus (3.00 microns 2), limiting FTC from other lesions (observed ranges: NG, 1.64-2.87 microns 2; FTA, 1.81-2.85 microns 2; FTC, 3.01-3.97 microns 2). Evaluation of the mean number of AgNORs per nucleus did not improve the diagnosis of malignancy. CONCLUSION: Computer-aided morphometric analysis of silver dots may be useful in the preoperative diagnosis of thyroid lesions.     

Graphical exploration of gene expression data: a comparative study of three multivariate methods

This article describes three multivariate projection methods and compares them for their ability to identify clusters of biological samples and genes using real-life data on gene expression levels of leukemia patients. It is shown that principal component analysis (PCA) has the disadvantage that the resulting principal factors are not very informative, while correspondence factor analysis (CFA) has difficulties interpreting distances between objects. Spectral map analysis (SMA) is introduced as an alternative approach to the analysis of microarray data. Weighted SMA outperforms PCA, and is at least as powerful as CFA, in finding clusters in the samples, as well as identifying genes related to these clusters. SMA addresses the problem of data analysis in microarray experiments in a more appropriate manner than CFA, and allows more flexible weighting to the genes and samples. Proper weighting is important, since it enables less reliable data to be down-weighted and more reliable information to be emphasized.     

Structural and thermodynamic studies of binding saturated fatty acids to bovine β-lactoglobulin

Lactoglobulin is a globular milk protein for which physiological function has not been clarified. Due to its binding properties lactoglobulin might serve as a carrier for bioactive molecules. Binding of 12-, 14-, 16- and 18-carbon saturated fatty acids to bovine β-lactoglobulin has been characterised by isothermal titration calorimetry and X-ray crystallography as a part of systematic studies of lactoglobulin complexes with ligands of biological importance. The thermodynamic parameters have been determined for lauric, myristic and palmitic acid complexes revealing systematic decrease of enthalpic and increase of entropic component of ΔG with elongation of aliphatic chain. In all crystal structures determined with resolution 1.9-2.1?, single fatty acid molecule was found in the β-barrel in extended conformation with individual pattern of interactions. Location of a fatty acid in the binding site depends on the length of aliphatic chain and influences polar interactions between protein and ligand. Systematic changes of entropic component indicate important role of water in binding process.     

Attack rates of seasonal epidemics

We study the attack rate, that is the total fraction of the population infected each year, for a disease with seasonally varying transmission rate. The attack rate is shown to be governed by both the reproductive number, reflecting the transmissibility of the disease, and the birth rate, which provides a source of new susceptibles. For the case of epidemics which have an annual period (like the seasonality), we prove inequalities which show that the attack rate is close to that of the non-seasonal model, so that it is nearly independent of the strength of the forcing, despite the fact that the shape of the epidemic curve depends strongly on the degree of seasonality of the forcing. Numerical simulations show that this holds to an even stronger extent than is implied by our rigorous results. When the system has subharmonic or chaotic solutions, we show that similar results hold when the attack rate is replaced by the average attack rate over several years. Consequences of these findings for analyzing the effect of vaccination in seasonally-forced models are noted.     

Investigating the effects of double mutation C30A/C75A on onconase structure: Studies at atomic resolution

The structure of onconase C30A/C75A double mutant has been determined at 1.12Å resolution. The structure has high structural homology to other onconase structures. The changes being results of mutation are relatively small, distributed asymmetrically around the two mutated positions, and they are observed not only in the mutation region but expanded to entire molecule. Different conformation of Lys31 side chain that influences the hydrogen bonding network around catalytic triad is probably responsible for lower catalytic efficiency of double mutant. The decrease in thermal stability observed for the onconase variant might be explained by a less dense packing as manifested by the increase of the molecular volume and the solvent accessible surface area. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 454–460, 2014.