Discovery of Potent Isoindolinone Inhibitors that Target an Active Conformation of PARP1 Using DNA-Encoded Libraries.

Inhibition of poly (ADP-ribose) polymerase-1 (PARP1), a DNA repair enzyme, has proven to be a successful strategy for the treatment of various cancers. With the appropriate selection conditions and protein design, DNA-encoded library (DEL) technology provides a powerful avenue to identify small molecules with the desired mechanism of action towards a target of interest. However, DNA-binding proteins, such as PARP1, can be challenging targets for DEL screening due to non-specific protein-DNA interactions.

Posterior Sagittal Approach for Nonanorectal Malformation: Widening Spectrum.

Background: Posterior sagittal is a very well accepted approach in the treatment of anorectal malformations. This approach provides good access and exposure through the perineum to the deep pelvic structures. It reduces risk of injury to important structures as dissection remains in midline.

Initial experience with 3D laparoscopic choledochal cyst (CDC) excision and hepatico-duodenostomy (HD) in 21 children.

Introduction: Minimal access surgery has gradually become the standard of care in the management of choledochal cysts (CDC). Laparoscopic management of CDC is a technically challenging procedure that requires advanced intracorporeal suturing skills, and hence, has a steep learning curve. Robotic surgery has the advantages of 3D vision, articulating hand instruments making suturing easy and thus is ideal.

Phomoxanthone A Targets ATP Synthase.

Phomoxanthone A is a naturally occurring molecule and a powerful anti-cancer agent, although its mechanism of action is unknown. To facilitate the determination of its biological target(s), we used affinity-based labelling using a phomoxanthone A probe. Labelled proteins were pulled down, subjected to chemoproteomics analysis using LC-MS/MS and ATP synthase was identified as a likely target.

An Unusual Case of Type A Posterior Cloaca Associated with 46XX Disorder of Sexual Differentiation with Y Duplication of Urethra.

We report an infant reared as a girl who presented with ambiguous genitalia and urine coming per rectum. On examination, she had minimal clitoromegaly with labial fusion and Y urethral duplication. On investigations, genetic, metabolic, and endocrine causes for disorder of sexual differentiation were ruled out.