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Studies of the biological influence and the adhesion properties of osteoclacin in the osteoclasts-like cells in humans show that osteoclacin activates bone sialoprotein (BSP), fibronectin and osteopontin secretion, induces clustering in beta3 and beta1 integrin chain adhesion and spreading of the osteoclast-like cells. Osteocalcin also activates chemotaxis depending on the dosage level. Thapsigargin-sensitive stores in the cells secrete intracellular calcium that regulates the effect of BSP on osteoclasts.

Anesthesia is used on a daily basis in Human medicine and for scientific research. Among anesthetic agents, ketamine and isoflurane are the most commonly used for intravenous and inhalation-induced anesthesia, respectively. Still, such anesthetics does affect cell homeostasis through cell signaling pathways with modulations of protein post-translational modifications (PTMs). O-GlcNAcylation (O-GlcNAc) is a ubiquitous PTM involved in many biological processes. Hirose et al. reported that isoflurane could induce an increase in O-GlcNAc levels. However, this study was not designed to specifically evaluate this aspect. Considering that O-GlcNAc stimulation is cardioprotective in acute pathologies, the increase in O-GlcNAc levels induced by anesthesia could potentially have unexpected impact on research projects. Our study aimed to evaluate whether (1) anesthesia influences O-GlcNAc and (2) O-GlcNAc stimulation affects physiological parameters in healthy rats. General anesthesia was performed on adult healthy males Wistar rats with either ketamine-xylazine (KX) or isoflurane (ISO) for one hour. Rats were injected either with Ringer Lactate or NButGT (KX + N, ISO + N) treatment (10 mg/kg) to increase O-GlcNAc levels. Upon sacrifice, hemodynamics parameters and plasmatic markers were evaluated, and heart was harvested. O-GlcNAc and O-GlcNAc-related enzymes levels were evaluated by western blot. As expected, isoflurane had lower impact on hemodynamics parameters. Surprisingly, anesthesia (neither ISO nor KX) had no impact on O-GlcNAc levels in the heart (KX: 0.90 ± 0.18; ISO: 0.87 ± 0.04; P < 0.05). Pharmacological stimulation of O-GlcNAc by NButGT efficiently increased O-GlcNAc levels in the heart (KX: 0.90 ± 0.18; KX + N: 1.22 ± 0.16; ISO: 0.87 ± 0.04; ISO + N: 1.32 ± 0.08; P < 0.05) and had no impact on physiological parameters such as heart rate, mean blood pressure, blood gazes, electrolytes or pH. These results prove that neither ketamine-xylazine nor isoflurane-induced anesthesia increase O-GlcNAc levels under standardized anesthetics conditions. Pharmacological stimulation of O-GlcNAc over a 1-hour period did not disrupt the physiological balance. We also confirm that on healthy rat, acute increase in O-GlcNAc levels does not impact cardiovascular parameters. [ABSTRACT FROM AUTHOR]

Many diseases are linked to an alteration of heart structure; however, 3D of the heart remain challenging particularly when you want to access samples for histology. A new serial block face imaging technique, faster than lightsheet and less expensive than micro-CT, was developed by Kaer Labs (The Kratoscope). The aim of this study was validated this simple technique to evaluate the role of O-GlcNAcylation, a post-translational modification, in cardiac development in rats and to save samples for histological analysis. The main objective was to build a 3D reconstruction of the heart to measure wall thickness (right ventricle-RV and left ventricle-LV), the volume of ventricles and trabeculae at embryonic stage 15.5 (E15,5) in control CTRL and NButGT treated group (10 mg/kg daily to the mother) to increase O-GlcNAc levels. Female Wistar rats received a daily subcutaneous injection of NButGT (10 mg/kg) during the protocole. Hearts of embryos were collected in formalin 10% at E15,5 and then incubated in Blue Evans (20 mg/mL) during 30 seconds and finally impregnated with O.C.T. The imaging system Kratoscope acquires an image of the organ every 5 μm slice, in a fully automated process. The 3D reconstruction is then built up with stack through Fiji and Imaris softwares. Each slice can be saved and store for further analysis. Thanks to the 3D reconstruction, we observed an alteration of the LV, in fact the volume of the LV increases in the tested group (CTRL: 0.53; NButGT: 0.72 mm3). The RV and LV walls are also thinner (CTRL: 0.28; NButGT: 0.19 mm3) which indicates the development of a cardiac hypertrophy. The septum and the volume of the trabeculae is thinner (CTRL: 0.15; NButGT: 0.07 mm3) and (CTRL: 0.12; NButGT: 0.06 mm3). The exterior volume of the RV remains unchanged (CTRL: 0.66; NButGT: 0.66 mm3). These results suggest the importance of O-GlcNAcylation during cardiac development. The Kratoscope is a suitable method for 3D reconstruction and histological analysis to reduce the number of animals. The advantage of this technique is to be able to recover a cut in a classic way when desired for 2D immunohistochemical studies. We can also imagine coupling this technique with the study of RNA in spatial transcriptomics Fig. 1. [ABSTRACT FROM AUTHOR]

O-GlcNAcylation, a post-translational modification, is involved in many cellular processes such as cell division, growth and transcription. It is regulated by a unique couple of enzymes: O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) which respectively removes and adds the GlcNAc moiety. Notably, the cardiospecific deletion of OGT results in defects in cardiac development. Interestingly, OGT gene is carried by the X chromosome; hence it could explain differences observed in cardiac dysfunction between male and female. Our team has demonstrated ex vivo that long-term increase in O-GlcNAc levels is associated with cardiomyocyte hypertrophy. We aim to decipher the role of O-GlcNAcylation on cardiac development. From the day before mating, till the end of pregnancy, female Wistar rats received a daily subcutaneous injection of NButGT (10 mg/kg) to increase O-GlcNAc levels. Embryos were collected at 15.5 and 20.5 days after mating (E15.5, E20.5) and 84 days after birth (D84). A morphological analysis of cardiac and body development was realized. PCR on SRY gene were done to know the sex. O-GlcNAc levels decrease significantly throughout development, from E15.5 to D84, (E15.5: 1.000 ± 0.055; D84: 0.046 ± 0.005; P < 0.001). NButGT increases O-GlcNAc levels in fetal heart at E15.5 and E20.5 (∼1.5 folds). At both times, the increase in O-GlcNAc levels is associated with morphological alteration of embryo, it affects their weight (E15.5: CTR: 271.9 ± 6.3; NButGT: 343.1 ± 32.8 mg; P < 0.05) and their height (E15.5: CTR: 12.7 ± 0.1; NButGT: 14.2 ± 0.3 mm; P < 0.001). NButGT treatment also alters cardiac structure, specifically, it increases the heart to embryo weight ratio (E20.5: CTR: 0.006 ± 0.0002; NButGT: 0.007 ± 0.0002; P < 0.5) in a sex independent manner. Our findings reveal that stimulate O-GlcNAcylation during development has an impact on global development and more particularly heart in a sex independent manner. We aim to assess the morphological consequences of heightened O-GlcNAcylation on the heart through histological analysis. Given the significant association between O-GlcNAcylation and diabetes, our results hold particular significance and may pave the way for new strategies to prevent cardiac hypertrophy in newborns born to diabetic mothers. [ABSTRACT FROM AUTHOR]

An attempt is made to establish a link between ordinary arithmetical situations and relevant mathematical concepts by the analyzing of complexity of concepts. (MP)

Examples are given of the variety of mathematical concepts and problems being studied by psychologically oriented researchers in France. Work on decimals, circles, natural numbers, decimal and real numbers, and didactic transposition are included. Comments on designing research on mathematics concept formation conclude the article. (MNS)