Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Regulates Translation of Type I Collagen mRNAs

Type I collagen is the most abundant protein in the human body and is composed of two α1(I) and one α2(I) polypeptides which assemble into a triple helix. For the proper assembly of the collagen triple helix, the individual polypeptides must be translated in coordination. Here, we show that serine-threonine kinase receptor-associated protein (STRAP) is tethered to collagen mRNAs by interaction with LARP6. LARP6 is a protein which directly binds the 5′ stem-loop (5′SL) present in collagen α1(I) and α2(I) mRNAs, but it interacts with STRAP with its C-terminal domain, which is not involved in binding 5′SL. Being tethered to collagen mRNAs, STRAP prevents unrestricted translation, primarily that of collagen α2(I) mRNAs, by interacting with eukaryotic translation initiation factor 4A (eIF4A). In the absence of STRAP, more collagen α2(I) mRNA can be pulled down with eIF4A, and collagen α2(I) mRNA is unrestrictedly loaded onto the polysomes. This results in an imbalance of synthesis of α1(I) and α2(I) polypeptides, in hypermodifications of α1(I) polypeptide, and in inefficient assembly of the polypeptides into a collagen trimer and their secretion as monomers. These defects can be partially restored by supplementing STRAP. Thus, we discovered STRAP as a novel regulator of the coordinated translation of collagen mRNAs.     

Chronic estradiol exposure modulates thyroid structure and decreases T4 and T3 serum levels in middle-aged female rats

OBJECTIVES: In human medicine, estrogen is applied in prevention and treatment of health problems associated with the menopause. The aim of this study was to examine the effects of chronic estradiol dipropionate (EDP) treatment on thyroid gland structure and function in middle-aged female rats. METHODS: At 14 months of age, Wistar rats received 0.625 mg EDP/kg b.w./day intraperitoneally for 2 weeks. The peripheral and central zones of the thyroid were stereologically analyzed and the following morphometric parameters determined: volume density of follicles, follicular epithelium, interstitium and colloid, epithelial height and the index of activation rate. Serum levels of TSH, T4 and T3 were determined by ELISA. RESULTS: EDP treatment led to significant decreases in volume densities of follicles and follicular epithelium, epithelial height and index of activation rate (by 11%, p < 0.05; 23%, p < 0.005; 11%, p < 0.05 and 21%, p < 0.05, respectively) in comparison to control values. Hyperplasia of thyroid follicular cells was noticed in 25% of EDP-treated animals. Serum levels of T4 and T3 were decreased (by 33%, p < 0.005 and 28%, p < 0.001, respectively), but TSH concentration was not significantly different from that of the controls. CONCLUSION: Chronic estradiol treatment significantly decreased volume density and height of centrally located follicular epithelium, follicular activation index and serum level of total thyroid hormones in middle-aged rats.     

Telomere length homeostasis is achieved via a switch between telomerase- extendible and -nonextendible states

Telomerase counteracts telomere erosion that stems from incomplete chromosome end replication and nucleolytic processing. A precise understanding of telomere length homeostasis has been hampered by the lack of assays that delineate the nonuniform telomere extension events of single chromosome molecules. Here, we measure telomere elongation at nucleotide resolution in Saccharomyces cerevisiae. The number of nucleotides added to a telomere in a single cell cycle varies between a few to more than 100 nucleotides and is independent of telomere length. Telomerase does not act on every telomere in each cell cycle, however. Instead, it exhibits an increasing preference for telomeres as their lengths decline. Deletion of the telomeric proteins Rif1 or Rif2 gives rise to longer telomeres by increasing the frequency of elongation events. Thus, by taking a molecular snapshot of a single round of telomere replication, we demonstrate that telomere length homeostasis is achieved via a switch between telomerase-extendible and -nonextendible states.     

Fitness level of adult economically active population in the Republic of Croatia estimated by EUROFIT system

The study presents the results of the EUROFIT CROATIA project that was conducted according to the instructions of Council of Europe. The aim of the study was evaluation of fitness level of the employed Croatian population. The measurements comprised EUROFIT battery of tests as well as Baecke's questionnaire for evaluation of habitual physical activity. The sample was comprised of 1628 active inhabitants, 18-60 years of age, all of who were employed and living in Croatia. The obtained results of functional, motor and morphological characteristics were presented according to the sex and age. The results shower poor aerobic capacity, high obesity indicators and low motor performance in both sexes, which pointed to the increased risk for developing many cardiovascular or musculo-skeletal diseases. The overall fitness level of Croatian population showed to be unsatisfactory and it should be improved by engagement in sports-recreational activities.     

Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation

Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (N^ω-nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.     

Nest as an extended phenotype signal of female quality in the great reed warbler

Extended phenotypes with signalling function are mostly restricted to animal taxa that use construction behaviour during courtship displays. However, they can be used also as post‐mating signals of mate quality, allowing individuals to obtain reliable information about their partners. Nest size may have such a signalling function and a lot of indirect evidence supports this view. However, direct evidence based on an experimental approach is still widely missing. Here we test the role of nest size in post‐mating signalling of mate quality in the great reed warbler Acrocephalus arundinaceus, a passerine with female‐restricted nest‐building behaviour. Based on observational data, clutch size, nestling weight, brood size and fledglings’ propensity to return to their natal site positively correlated with nest size. Moreover, we experimentally enlarged great reed warbler nests to investigate whether this manipulation affects male investment in feeding. We found that males fed their nestlings significantly more intensively on enlarged nests than those on control nests. This suggests that nest size in this species serves as a signal of female quality or willingness to invest in reproduction and that it pays males to enhance their feeding effort according to this signal. Thus, we provide convincing evidence that animal communication takes place through the extended phenotypes and that post‐mating signalling of quality is not restricted only to males, but may function equally well in females.     

Autophagy proteins stabilize pathogen-containing phagosomes for prolonged MHC II antigen processing

Antigen preservation for presentation is a hallmark of potent antigen-presenting cells. In this paper, we report that in human macrophages and dendritic cells, a subset of phagosomes gets coated with Atg8/LC3, a component of the molecular machinery of macroautophagy, and maintains phagocytosed antigens for prolonged presentation on major histocompatibility complex class II molecules. These Atg8/LC3-positive phagosomes are formed around the antigen with TLR2 agonists and require reactive oxygen species production by NOX2 for their generation. A deficiency in the NOX2-dependent formation of these antigen storage phagosomes could contribute to compromise antifungal immune control in chronic granulomatous disease patients.