TGS1/PIMT knockdown reduces lipid accumulation in adipocytes, limits body weight gain and promotes insulin sensitivity in mice.

PRIP Interacting protein with Methyl Transferase domain (PIMT/TGS1) is an integral upstream coactivator in the peroxisome proliferator-activated receptor gamma (PPARγ) transcriptional apparatus. PPARγ activation alleviates insulin resistance but promotes weight gain. Herein, we show how PIMT regulates body weight while promoting insulin sensitivity in diet induced obese mice.

Wang resin catalysed sonochemical synthesis of pyrazolo[4,3-d]pyrimidinones and 2,3-dihydroquinazolin-4(1H)-ones: Identification of chorismate mutase inhibitors having effects on Mycobacterium tuberculosis cell viability.

The enzyme chorismate mutase (or CM that is vital for the survival of bacteria) is an interesting pharmacological target for the identification of new anti-tubercular agents. The 5,5-disibstituted pyrazolo[4,3-d]pyrimidinone derivatives containing the fragment based on 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide were designed and explored as the potential inhibitors of chorismate mutase. Based on encouraging docking results of two representative molecules evaluated in silico against MtbCM (PDB: 2FP2) the Wang resin catalysed sonochemical synthesis of target N-heteroarenes were undertaken.

PIMT regulates hepatic gluconeogenesis in mice.

The physiological and metabolic functions of PIMT/TGS1, a third-generation transcriptional apparatus protein, in glucose homeostasis sustenance are unclear. Here, we observed that the expression of PIMT was upregulated in the livers of short-term fasted and obese mice. Lentiviruses expressing Tgs1-specific shRNA or cDNA were injected into wild-type mice.

Pd/Cu-catalyzed access to novel 3-(benzofuran-2-ylmethyl) substituted (pyrazolo/benzo)triazinone derivatives: their / evaluation as inhibitors of chorismate mutase (CM).

In view of the reported chorismate mutase (CM or CM) inhibitory activities of 3-indolylmethyl substituted (pyrazolo/benzo)triazinone derivatives the structurally similar 3-(benzofuran-2-ylmethyl) substituted (pyrazolo/benzo)triazinones were designed and evaluated against CM. The docking of target molecules was performed at the interface site of CM (PDB: 2FP2). All the best ranked molecules participated in a strong H-bonding with the ILE67 of the B chain at the backbone position in addition to several hydrophobic/van der Waals interactions with the hydrophobic residues.

PIMT/TGS1: An evolving metabolic molecular switch with conserved methyl transferase activity.

Transcriptional coactivators play a crucial role in regulating gene expression. PRIP interacting protein with methyl transferase domain (PIMT)/trimethyl guanosine synthase 1 (TGS1) is a co-activator interacting protein with an RNA methyl transferase domain. PIMT serves as a bridge between HAT and non-HAT coactivators and differentially modulates gene expression.

Rosuvastatin based novel 3-substituted isocoumarins / 3-alkylidenephthalides: Ultrasound assisted synthesis and identification of new anticancer agents.

A new class of 3-substituted isocoumarin/3-alkylidenephthalide based novel small molecules derived from rosuvastatin were designed and synthesized via the ultrasound assisted Cu-mediated coupling-cyclization in a single pot with remarkable regioselectivity. The phthalides were generally obtained at lower temperature whereas the use of elevated temperature afforded isocoumarins. Two compounds e.

Novel isatin-indole derivatives as potential inhibitors of chorismate mutase (CM): their synthesis along with unexpected formation of 2-indolylmethylamino benzoate ester under Pd-Cu catalysis.

A series of novel isatin-indole derivatives has been designed as potential inhibitors of chorismate mutase (CM) that is known to be present in bacteria, fungi and higher plants but not in human. The design was supported by docking studies that predicted strong interactions of these molecules with CM. The target compounds were synthesized the one-pot coupling/cyclization method involving the reaction of an isatin based terminal alkyne with 2-iodosulfanilides under Pd-Cu catalysis.

Synthesis of 3-indolylmethyl substituted (pyrazolo/benzo)triazinone derivatives under Pd/Cu-catalysis: Identification of potent inhibitors of chorismate mutase (CM).

The chorismate mutase (CM) is considered as an attractive target for the identification of potential antitubercular agents due to its absence in animals but not in bacteria. A series of 3-indolylmethyl substituted pyrazolotriazinone derivatives were designed and docked into CM in silico as potential inhibitors. These compounds were efficiently synthesized using the Pd/Cu-catalyzed coupling-cyclization in a single pot involving the construction of indole ring.

Mycobacterium tuberculosis chorismate mutase: A potential target for TB.

Mycobacterium tuberculosis chorismate mutase (MtbCM) catalyzes the rearrangement of chorismate to prephenate in the shikimate biosynthetic pathway to form the essential amino acids, phenylalanine and tyrosine. Two genes encoding chorismate mutase have been identified in Mtb. The secretory form,∗MtbCM (encoded by Rv1885c) is assumed to play a key role in pathogenesis of tuberculosis.

The singing teacher as vocal parent.

Vocal parenting is a pedagogical approach that views the teaching of singing to children as a nurturing process. It encompasses the development of fundamentally sound vocal technique, guidance in repertoire selection and performance practices, and concern for the physical, mental, and emotional well-being of the child as a singer, performer, and person. Role-play and storytelling are among the strategies employed to fully integrate vocal technique with the personality of the singer.

Stripe stacker for use with laser diode bars.

An optical device that reconfigures the output of a laser diode bar source to a more compact pointlike format is described. The design is an adaptation of image slicers used for many years in astronomical spectroscopy and has the advantages of simple construction and high efficiency.

Refractive index measurements of ten germanium samples.

The refractive index of germanium was measured for ten samples, covering the various crystal types, over the 8-14-microm wavelength range. Samples were obtained from several suppliers, and differences between samples in the index values reported were not significant compared with the estimated index uncertainties of +/-0.0003.

Refractive index measurements of a germanium sample.

The refractive index of a germanium prism was measured by two different laboratories for wavelengths in the 8-14-microm range. The sample was a single crystal of known purity and growth history. Index results from the two experiments agreed to within 0.

Infrared interferometer with a scanned aperture.

A Twyman-Green interferometer operating at a 3.39-microm wavelength has been built in which the collimator aperture was scanned by a laser beam. The scanning was produced by reflecting the laser beam from a mirror supported by four piezoelectric elements and oscillated about two orthogonal axes.