High serum circulating telopeptide type I in multinodular goiter.

Recently, concentrations of serum carboxy-terminal-1-telopeptide (ICTP), a marker of bone collagen resorption, were found to be more sensitive than sex hormone-binding globulin (SHBG) in identifying peripheral overexposure to thyroid hormones in exogenous subclinical hyperthyroidism. The aim of the present study was to assess serum ICTP and SHBG in multinodular goiter with (pretoxic goiter) or without biochemical evidence of endogenous subclinical hyperthyroidism. Forty-five women affected by multinodular goiter were enrolled in this study. They were subdivided into two groups: group 1, consisting of 27 patients affected by pretoxic goiter; group 2, consisting of 18 patients affected by non toxic goiter; group 3, consisting of thirty-six euthyroid women matched with the other groups for age and lifestyle. In group 1, serum ICTP (mean +/- SD: 5.8 +/- 2.9 microg/l) concentrations were significantly higher when compared either to group 2 (3.6 +/- 1.2 microg/l; p < 0.02) or controls (2.7 +/- 0.7 microg/l; p < 0.0001); serum ICTP concentrations were also slightly but significantly higher in patients of group 2 compared to controls (p < 0.003). In contrast, mean serum SHBG concentrations did not show any difference among the three groups. No significant correlation was found between serum TSH and ICTP concentrations, while a weak positive correlation (p < 0.05) was only found between serum FT 3 and ICTP concentrations when data from the two patient groups were analyzed together. Moreover, when we subdivided patients into pre- and postmenopausal patients, we observed that SHBG but not ICTP serum concentrations were influenced by estrogenic status. In summary, the measurement of serum ICTP seems to be more suitable than SHBG for identifying those with a higher degree of peripheral thyroid hormone exposure in women affected by endogenous subclinical hyperthyroidism.     

DNA methylation‐based biomarkers of aging were slowed down in a two‐year diet and physical activity intervention trial: the DAMA study

Several biomarkers of healthy aging have been proposed in recent years, including the epigenetic clocks, based on DNA methylation (DNAm) measures, which are getting increasingly accurate in predicting the individual biological age. The recently developed “next‐generation clock” DNAmGrimAge outperforms “first‐generation clocks” in predicting longevity and the onset of many age‐related pathological conditions and diseases. Additionally, the total number of stochastic epigenetic mutations (SEMs), also known as the epigenetic mutation load (EML), has been proposed as a complementary DNAm‐based biomarker of healthy aging. A fundamental biological property of epigenetic, and in particular DNAm modifications, is the potential reversibility of the effect, raising questions about the possible slowdown of epigenetic aging by modifying one''s lifestyle. Here, we investigated whether improved dietary habits and increased physical activity have favorable effects on aging biomarkers in healthy postmenopausal women. The study sample consists of 219 women from the “Diet, Physical Activity, and Mammography” (DAMA) study: a 24‐month randomized factorial intervention trial with DNAm measured twice, at baseline and the end of the trial. Women who participated in the dietary intervention had a significant slowing of the DNAmGrimAge clock, whereas increasing physical activity led to a significant reduction of SEMs in crucial cancer‐related pathways. Our study provides strong evidence of a causal association between lifestyle modification and slowing down of DNAm aging biomarkers. This randomized trial elucidates the causal relationship between lifestyle and healthy aging‐related epigenetic mechanisms.     

Evolution at the tip and base of the X chromosome in an African population of Drosophila melanogaster

Hitchhiking effects of advantageous mutations have been invoked to explain reduced polymorphism in regions of low crossing-over in Drosophila. Besides reducing DNA heterozygosity, hitchhiking effects should produce strong linkage disequilibrium and a frequency spectrum skewed toward an excess of rare polymorphisms (compared to the neutral expectation). We measured DNA polymorphism in a Zimbabwe population of D. melanogaster at three loci, yellow, achaete, and suppressor of forked, located in regions of reduced crossing-over. Similar to previously published surveys of these genomic regions in other populations, we observed low levels of nucleotide variability. However, the frequency spectrum was compatible with a neutral model, and there was abundant evidence for recombination in the history of the yellow and ac genes. Thus, some aspects of the data cannot be accounted for by a simple hitchhiking model. An alternative hypothesis, background selection, might be compatible with the observed patterns of linkage disequilibrium and the frequency spectrum. However, this model cannot account for the observed reduction in nucleotide heterozygosity. Thus, there is currently no satisfactory theoretical model for the data from the tip and base of the X chromosome in D. melanogaster.      

Short chain oligogalacturonides induce ethylene production and expression of the gene encoding aminocyclopropane 1-carboxylic acid oxidase in tomato plants

Oligogalacturonic acids (OGAs), derived from plant cell wall pectin, have been implicated in a number of signal transduction pathways involved in growth, development and defense responses of higher plants. This study investigates the size range of OGAs capable of inducing ethylene synthesis in tomato plants, and demonstrates that in contrast with many other effects, only short chain OGAs are active. Oligomers across a range of DP from 2-15 were separated and purified to homogeneity by QAE-Sephadex anion exchange chromatography using a novel elution system. The OGAs were applied to tomato plants and assayed for their ability to induce ethylene gas release and changes in steady state levels of mRNA encoding the ethylene forming enzyme aminocyclopropane-1-carboxylic acid oxidase (ACO). The study demonstrated that only OGAs in the size range of DP4-6 were active both in eliciting ACO expression and in the production of ethylene.      

A change in twist of actin provides the force for the extension of the acrosomal process in limulus sperm: the false-discharge reaction

One of the most spectacular motions is the generation of the acrosomal process in the limulus sperm. On contact with the egg, the sperm generates a 60-mum-long process that literally drills its way through the jelly surrounding the egg. This irresversible reaction takes only a few seconds. We suggested earlier that this motion is driven by a change in twist of the actin filaments comprising the acrosomal process. In this paper we analyze the so-called false discharge, a reversible reaction, in which the acrosomal filament bundle extends laterally from the base of the sperm and not anteriorly from the apex. Unlike the true discharge, which is straight, the false discharge is helical. Before extension, the filament bundle is coiled about the base of the sperm. In the coil, the bundle is not smoothly bent but consists of arms (straight segments) and elbows (corners) so that the coil looks like a 14-sided polygon. The extension of the false discharge works as follows: starting at the base of the bundle, the filaments change their twist which concomitantly changes the orientations of the elbows relative to each other; that is, in the coil, the elbows all like in a common plane, but after the change in twist, the plane of each elbow is rotated to be perpendicular to that of its neighbors. This change transforms the bundle from a compact coil into an extended left- handed helix. Because the basal end of the bundle is unconstrained, the extension is lateral. The true discharge works the same way but starts at the apical end of the bundle. The apical end, however, is constrained by its passage through the nuclear canal, which directs the extention anteriorly. Unlike the false discharge, during the true discharge the elbows are melted out, making the reaction irreversible. This study shows that rapid movement can be regenerated by actin without myosin and gives us insight into the molecular mechanism.