First-Trimester Follistatin-Like-3 Levels in Pregnancies Complicated by Subsequent Gestational Diabetes Mellitus

Objective: To determine whether maternal levels of follistatin-like-3 (FSTL3), an inhibitor of activin and myostatin involved in glucose homeostasis, are altered in the first trimester of pregnancies complicated by subsequent gestational diabetes mellitus (GDM). Research Design and Methods: This was a nested case-control study of subjects enrolled in a prospective cohort of pregnant women with and without GDM ($\geq$2 abnormal values on a 100-g glucose tolerance test at ~28 weeks of gestation). We measured FSTL3 levels in serum collected during the first trimester of pregnancy. Logistic regression analyses were used to determine the risk of GDM. Results: Women who developed GDM (n = 37) had lower first-trimester serum levels of FSTL3 compared with women who did not (n = 127) (median 10,789 [interquartile range 7,013-18,939] vs. 30,670 [18,370-55,484] pg/ml, P < 0.001). When subjects were divided into tertiles based on FSTL3 levels, women with the lowest levels demonstrated a marked increase in risk for developing GDM in univariate (odds ratio 11.2 [95% CI 3.6-35.3]) and multivariate (14.0 [4.1-47.9]) analyses. There was a significant negative correlation between first-trimester FSTL3 levels and ~28-week nonfasting glucose levels (r = -0.30, P < 0.001). Conclusions: First-trimester FSTL3 levels are associated with glucose intolerance and GDM later in pregnancy

Follistatin-like 3 (FSTL3) mediated silencing of transforming growth factor (TGF ) signaling is essential for testicular aging and regulating testis size

Follistatin-like 3 (FSTL3) is a glycoprotein that binds and inhibits the action of TGFβ ligands such as activin. The roles played by FSTL3 and activin signaling in organ development and homeostasis are not fully understood. The authors show mice deficient in FSTL3 develop markedly enlarged testes that are also delayed in their age-related regression. These FSTL3 knockout mice exhibit increased Sertoli cell numbers, allowing for increased spermatogenesis but otherwise showing normal testicular function. The data show that FSTL3 deletion leads to increased AKT signaling and SIRT1 expression in the testis. This demonstrates a cross-talk between TGFβ ligand and AKT signaling and leads to a potential mechanism for increased cellular survival and antiaging. The findings identify crucial roles for FSTL3 in limiting testis organ size and promoting age-related testicular regression

Differential expression of follistatin and FLRG in human breast proliferative disorders

<p>Abstract</p> <p>Background</p> <p>Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG) bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases.</p> <p>Methods</p> <p>Paraffin embedded specimens of normal breast (NB - n = 8); florid hyperplasia without atypia (FH - n = 17); fibroadenoma (FIB - n = 17); ductal carcinoma <it>in situ </it>(DCIS - n = 10) and infiltrating ductal carcinoma (IDC - n = 15) were processed for follistatin and FLRG immunohistochemistry and <it>in situ </it>hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively.</p> <p>Results</p> <p>Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed.</p> <p>Conclusion</p> <p>The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the present findings indicate that an increased FST and FLRG expression in breast proliferative diseases might counteract the anti-proliferative effects of activin in human breast cancer.</p

Позиционный электропривод механизма перемещения

Объектом исследования является позиционный асинхронный электропривод механизма горизонтального перемещения груза. Цель работы – исследовать основные характеристики асинхронного электропривода с трехконтурной системой управления положением вала двигателя. В процессе исследования проводились выбор асинхронного двигателя для механизма перемещения, расчет параметров двигателя, его статических и динамических характеристик, выбор преобразователя частоты, синтез трехконтурной системы управления следящим электроприводом на базе регулируемого с векторным управлением.The object of the study is a positional asynchronous electric drive mechanism for the horizontal movement of cargo. The purpose of the work is to investigate the basic characteristics of an asynchronous electric drive with a three-circuit control system for positioning the motor shaft. In the process of research, the choice of an asynchronous motor for the displacement mechanism, calculation of the engine parameters, its static and dynamic characteristics, choice of a frequency converter, synthesis of a three-circuit control system for a servomotor drive based on an adjustable vector control were made

Activin regulates \u3b2A-subunit and activin receptor messenger ribonucleic acid and cellular proliferation in activin-responsive testicular tumor cells

Activin, a member of the transforming growth factor-\u3b2 superfamily of growth and differentiation factors, has a number of actions in embryonic as well as adult tissues. These actions are mediated via a family of receptors containing two subtypes and at least two members of each subtype. Recent evidence demonstrates that activin-responsive cell lines containing different subsets of these receptors are valuable models for dissecting functional relationships among receptor subtype, signal transduced, and response obtained. TT cells, derived from a p53 (/-)/\u3b1-inhibin(-/-) mouse testicular tumor, respond to activin by proliferating, a response that can be inhibited by follistatin (FS) treatment. Using semiquantitative RT-PCR methods, we characterized steady state messenger RNA (mRNA) levels for the inhibin/activin subunits, FS, and activin receptor subtypes under basal conditions and in the presence of activin or FS. These cells produced ample immunoreactive activin A and FS, necessitating higher treatment doses to observe any modulation of cellular proliferation. Furthermore, in the presence of exogenous activin, mRNA levels for activin receptor type IIA (ACTRIIA) and \u3b2A were significantly and profoundly suppressed. In addition, both ACTR1B and ACTRIIB were detectable and down-regulated by exogenous activin, although not to the degree observed for ACTRIIA and \u3b2A. Finally, activin treatment at the higher doses, which decreased activin receptor mRNA levels, resulted in inhibition of cellular proliferation. Taken together with previous observations, our results support the model that these tumor cells respond to an autocrine activin signal by proliferating, whereas exogenous or excess activin results in down-regulation of activin receptor and activin biosynthesis, suggesting a potential autocrine/paracrine mechanism by which activin can modulate its own signal