Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

The Receptor Tyrosine Kinase FGFR4 Negatively Regulates NF-kappaB Signaling

NFκB signaling is of paramount importance in the regulation of apoptosis, proliferation, and inflammatory responses during human development and homeostasis, as well as in many human cancers. Receptor Tyrosine Kinases (RTKs), including the Fibroblast Growth Factor Receptors (FGFRs) are also important in development and disease. However, a direct relationship between growth factor signaling pathways and NFκB activation has not been previously described, although FGFs have been known to antagonize TNFα-induced apoptosis. assays. FGF19 stimulation of endogenous FGFR4 in TNFα-treated DU145 prostate cancer cells also leads to a decrease in IKKβ activity, concomitant reduction in NFκB nuclear localization, and reduced apoptosis. Microarray analysis demonstrates that FGF19 + TNFα treatment of DU145 cells, in comparison with TNFα alone, favors proliferative genes while downregulating genes involved in apoptotic responses and NFκB signaling.These results identify a compelling link between FGFR4 signaling and the NFκB pathway, and reveal that FGFR4 activation leads to a negative effect on NFκB signaling including an inhibitory effect on proapoptotic signaling. We anticipate that this interaction between an RTK and a component of NFκB signaling will not be limited to FGFR4 alone

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Validated High Performance Thin Layer Chromatographic Determination and Content Uniformity Test for Rosiglitazone in Tablets

A simple, rapid, precise and economical high performance thin layer chromatographic method has been developed and validated for determination of rosiglitazone in its tablet dosage form using caffeine as an internal standard. It was performed on silica gel 60 GF254 thin layer chromatographic plates as a stationary phase using mobile phase methanol:toluene:chloroform:triethylamine (1:8:0.5:0.5 v/v/v/v) and the detection was carried out in the absorbance mode at 264 nm showing Rf value 0.31 for rosiglitazone and 0.52 for caffeine. The linear regression data curve shows good linear relationship in the concentration range 1.0-7.0 µg/µl. The content uniformity test was carried out as per USP specification of the content uniformity test of 85-115%. The percent drug estimated of rosiglitazone from two different marketed formulations were found to be in the range 99.83-100.21. The recovery of drugs was carried out by standard addition method were found to be 100.21±1.06 and 100.04±0.30 by height and area respectively. The method was validated with the determination of accuracy, precision, specificity, linearity detector response and ruggedness. The proposed method provides a faster and cost effective quality control tool for routine analysis of content uniformity test for rosiglitazone in tablet formulation