Dynamic nuclear architecture and chromatin organizations are the key features of the mid‐prophase I in mammalian meiosis. The chromatin undergoes major changes, including meiosis‐specific ...spatiotemporal arrangements and remodeling, the establishment of chromatin loop–axis structure, pairing, and crossing over between homologous chromosomes, any deficiencies in these events may induce genome instability, subsequently leading to failure to produce gametes and infertility. Despite the significance of chromatin structure, little is known about the location of chromatin marks and the necessity of their balance during meiosis prophase I. Here, we show a thorough cytological study of the surface‐spread meiotic chromosomes of mouse spermatocytes for H3K9,14,18,23,27,36, H4K12,16 acetylation, and H3K4,9,27,36 methylation. Active acetylation and methylation marks on H3 and H4, such as H3K9ac, H3K14ac, H3K18ac, H3K36ac, H3K56ac, H4K12ac, H4K16ac, and H3K36me3 exhibited pan‐nuclear localization away from heterochromatin. In comparison, repressive marks like H3K9me3 and H3K27me3 are localized to heterochromatin. Further, taking advantage of the delivery of small‐molecule chemical inhibitors methotrexate (heterochromatin enhancer), heterochromatin inhibitor, anacardic acid (histone acetyltransferase inhibitor), trichostatin A (histone deacetylase inhibitor), IOX1 (JmjC demethylases inhibitor), and AZ505 (methyltransferase inhibitor) in seminiferous tubules through the rete testis route, revealed that alteration in histone modifications enhanced the centromere mislocalization, chromosome breakage, altered meiotic recombination and reduced sperm count. Specifically, IOX1 and AZ505 treatment shows severe meiotic phenotypes, including altering chromosome axis length and chromatin loop size via transcriptional regulation of meiosis‐specific genes. Our findings highlight the importance of balanced chromatin modifications in meiotic prophase I chromosome organization and instability.
Total intravenous anesthesia with propofol can be administered by target-controlled infusion pumps, which work on the principles of pharmacokinetic modeling. While designing this model, neurosurgical ...patients were excluded as the surgical site and drug action site remained the same (brain). Whether the predicted set propofol concentration and the actual brain site concentration correlate, especially in neurosurgical patients with impaired blood-brain barrier (BBB), is still unknown. In this study we compared the set propofol effect-site concentration in the target-controlled infusion pump with actual brain concentration measured by sampling the cerebrospinal fluid (CSF).
Consecutive adult neurosurgical patients requiring propofol infusion intraoperatively were recruited. Blood and CSF samples were collected simultaneously when patients received propofol infusion at 2 different target effect-site concentrations-2 and 4 ug/mL. To study BBB integrity, CSF-to-blood albumin ratio and imaging findings were compared. The propofol level in the CSF was compared with set concentration using the Wilcoxon signed-rank test.
Fifty patients were recruited, and the data were analyzed from 43 patients. There was no correlation between propofol concentration set in TCI and propofol concentration measured in blood and CSF. Though imaging findings were suggestive of BBB disruption in 37/43 patients, the mean (±standard deviation) CSF-to-serum albumin ratio was 0.0028 ± 0.002, suggesting intact BBB integrity (ratio >0.3 was considered as disrupted BBB).
CSF propofol level did not correlate with set concentration in spite of acceptable clinical anesthetic effect. Also, the CSF-to-blood albumin measurement did not provide information on the BBB integrity.
Pouchoscopy provides a critical objective measure in the evaluation of patients with suspected inflammatory conditions of the pouch; however, there remain significant gaps in the reliability of the ...endoscopic scales used in the assessment of these conditions.
Reliability and reproducibility in the assessment of patients after ileal pouch-anal anastomosis (IPAA) are critical, as evidenced by recent efforts to improve standardization in the evaluation of patients with pouch-related disorders.
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Death is the fate of postovulatory aged or unfertilized oocytes (POAO) in many animals. However, precise molecular mechanisms are yet to be discovered. Here, we demonstrate that increased amounts of ...reactive oxygen species (ROS), calcium ion (Ca+2) channels, and retrotransposon activity induce apoptosis, which in turn causes POAO death. Notably, suppression of ROS, Ca+2 channels, and retrotransposons delayed POAO death. Further, we found that the histone H4K12 and K16 acetylation increased via downregulation of NAD+ and NAD+ -dependent histone deacetylase SIRT3. Furthermore, adding NMN, sodium pyruvate, or CD38 inhibition delayed the death of postovulatory aged oocytes. Finally, we demonstrate the conservation of retrotransposon-induced DNA damage-dependent POAO death in higher-order vertebrates. Our findings suggest that POAO mortality is caused by cyclic cascade metabolic interactions in which low NAD+ levels increase histone acetylation by inhibiting histone deacetylases, resulting in an increase in retrotransposons, ROS, and Ca+2 channel activity and thus contributing to DNA damage-induced apoptosis.
Planar, 1D and hydrogen-bonded chains of benzimidazole molecules have been fabricated through surface-assisted self-assembly on Ag(111) and Au(111) and investigated with scanning tunneling ...microscopy. The hydrogen bond between the benzimidazoles and the coupling to the molecular π-electron system, of the type −CN···H–N–C, which exists in bulk crystals and gives rise to ferroelectricity at room temperature, is also observed in the supported 1D chains. Inspired by this finding, the proton-transfer mechanism in 1D chains of benzimidazoles in the gas phase and on coinage metal surfaces was investigated with density functional theory (DFT) calculations. It is demonstrated that the proton transfer, which is needed to reverse the dipole moment along a model chain, is a low-energy process in the gas phase. The substrate shapes this energy barrier and lowers it as compared with free chains. A hydrogen-transfer pathway via a tautomerized state is identified, and because of the relative instability of the tautomerized state, a concerted or cascaded proton transfer along the chains seems plausible. This study predicts that 1D organic ferroelectrics based on benzimidazoles can exist if the molecule–substrate interactions are appropriately controlled.
