Infraclavicular brachial plexus block: Comparison of posterior cord stimulation with lateral or medial cord stimulation, a prospective double blinded study

Background: Infraclavicular approach to the brachial plexus sheath provides anesthesia for surgery on the distal arm, elbow, forearm, wrist, and hand. It has been found that evoked distal motor response or radial nerve-type motor response has influenced the success rate of single-injection infraclavicular brachial plexus block. Aim: We conducted this study to compare the extent and effectiveness of infraclavicular brachial plexus block achieved by injecting a local anesthetic drug after finding specific muscle action due to neural stimulator guided posterior cord stimulation and lateral cord/medial cord stimulation. Methods: After ethical committee approval, patients were randomly assigned to one of the two study groups of 30 patients each. In group 1, posterior cord stimulation was used and in group 2 lateral/medial cord stimulation was used for infraclavicular brachial plexus block. The extent of motor block and effectiveness of sensory block were assessed. Results: All four motor nerves that were selected for the extent of block were blocked in 23 cases (76.7%) in group 1 and in 15 cases (50.0%) in group 2 (P:0.032). The two groups did not differ significantly in the number of cases in which 0, 1, 2, and 3 nerves were blocked (P>0.05). In group 1, significantly lesser number of patients had pain on surgical manipulation compared with patients of group 2 (P:0.037). Conclusion: Stimulating the posterior cord guided by a nerve stimulator before local anesthetic injection is associated with greater extent of block (in the number of motor nerves blocked) and effectiveness of block (in reporting no pain during the surgery) than stimulation of either the lateral or medial cord

Structural insights into histone chaperone Asf1 and its characterization from Plasmodium falciparum

Asf1 is a highly conserved histone chaperone that regulates tightly coupled nucleosome assembly/disassembly process. We observed that Plasmodium falciparum Asf1 (PfAsf1) is ubiquitously expressed in different stages of the life cycle of the parasite. To gain further insight into its biological activity, we solved the structure of N-terminal histone chaperone domain of PfAsf1 (1–159 amino acids) by X-ray crystallography to a resolution of 2.4 Å. The structure is composed of two beta-sheet to form a beta-sandwich, which resembles an immunoglobulin-like fold. The surface-charge distribution of PfAsf1 is distinct from yAsf1 and hAsf1 although the core-structure shows significant similarity. The crystal-structure indicated that PfAsf1 may exist in a dimeric-state which was further confirmed by solution cross-linking experiment. PfAsf1 was found to specifically interact with Plasmodium histone H3 and H4 and was able to deposit H3/H4 dimer onto DNA-template to form disomes, showing its characteristic histone chaperone activity. We mapped the critical residues of PfAsf1 involved in histone H3/H4 interaction and confirmed by site-directed mutagenesis. Further analysis indicates that histone interacting surface of Asf1 is highly conserved while the dimerization interface is variable. Our results identify the role of PfAsf1 as a mediator of chromatin assembly in Plasmodium falciparum, which is the causative agent of malignant malaria in humans

Atypical plant homeodomain of UBR7 functions as an H2BK120Ub ligase and breast tumor suppressor

H2B monoubiquitination is implicated in oncogenesis. Here, the authors show that UBR7 PHD finger is a H2BK120 monoubiquitin ligase that acts a tumour suppressor in breast cancer by suppressing gene expression for EMT, while promoting expression of CDH4 which restrain WNT/β-cat pathway

Dual histone reader ZMYND8 inhibits cancer cell invasion by positively regulating epithelial genes

Enhanced migratory potential and invasiveness of cancer cells contribute crucially to cancer progression. These phenotypes are achieved by precise alteration of invasionassociated genes through local epigenetic modifications which are recognized by a class of proteins termed a chromatin reader. ZMYND8 [zinc finger MYND (myeloid, Nervy and DEAF-1)-type containing 8], a key component of the transcription regulatory network, has recently been shown to be a novel reader of H3.1K36Me2/H4K16Ac marks. Through differential gene expression analysis upon silencing this chromatin reader, we identified a subset of genes involved in cell proliferation and invasion/migration regulated by ZMYND8. Detailed analysis uncovered its antiproliferative activity through BrdU incorporation, alteration in the expression of proliferation markers, and cell cycle regulating genes and cell viability assays. In addition, performing wound healing and invasion/migration assays, its anti-invasive nature is evident. Interestingly, epithelial–mesenchymal transition (EMT), a key mechanism of cellular invasion, is regulated by ZMYND8 where we identified its selective enrichment on promoters of CLDN1/CDH1 genes, rich in H3K36Me2/ H4K16Ac marks, leading to their up-regulation. Thus, the presence of ZMYND8 could be implicated in maintaining the epithelial phenotype of cells. Furthermore, syngeneic mice, injected with ZMYND8-overexpressed invasive breast cancer cells, showed reduction in tumor volume and weight. In concert with this, we observed a significant down-regulation of ZMYND8 in invasive ductal and lobular breast cancer tissues compared with normal tissue. Taken together, our study elucidates a novel function of ZMYND8 in regulating EMT and invasion of cancer cells, possibly through its chromatin reader function