Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation

Background  

Rett syndrome (RTT), a common cause of mental retardation in girls, is associated with mutations in the MECP2 gene. Most human cases of MECP2 mutation in girls result in classical or variant forms of RTT. When these same mutations occur in males, they often present as severe neonatal encephalopathy. However, some MECP2 mutations can also lead to diseases characterized as mental retardation syndromes, particularly in boys. One of these mutations, A140V, is a common, recurring missense mutation accounting for about 0.6% of all MeCP2 mutations and ranking 21^st by frequency. It has been described in familial X-linked mental retardation (XLMR), PPM- X syndrome (Parkinsonism, Pyramidal signs, Macroorchidism, X-linked mental retardation) and in other neuropsychiatric syndromes. Interestingly, this mutation has been reported to preserve the methyl-CpG binding function of the MeCP2 protein while compromising its ability to bind to the mental retardation associated protein ATRX.     

Microwave-assisted synthesis of 1-aryl-1H-indazoles via one-pot two-step Cu-catalyzed intramolecular N-arylation of arylhydrazones

A highly efficient one-pot two-step microwave procedure was developed for the synthesis of 1-aryl-1H-indazoles. Microwave heating of 2-halobenzaldehydes or 2-haloacetophenones with phenylhydrazines at 160 °C for 10 min quantitatively yielded the arylhydrazones, which were further cyclized to give 1-aryl-1H-indazoles via CuI/diamine-catalyzed N-arylation under microwave heating (160 °C, 10 min). Good to excellent yields were observed for 2-iodo, 2-bromo, and 2-chloro benzaldehydes or acetophenones.     

Process Improved Preparation of a Versatile α-Ketoester Acyl Anion Synthon

An improved scalable procedure for preparation of an α-ketoester acyl anion synthon is described.     

Guide to enantioselective dirhodium(II)-catalyzed cyclopropanation with aryldiazoacetates

Catalytic enantioselective methods for the generation of cyclopropanes have been of long standing pharmaceutical interest. Chiral dirhodium(II) catalysts prove to be an effective means for the generation of diverse cyclopropane libraries. Rh₂(R-DOSP)₄ is generally the most effective catalyst for asymmetric intermolecular cyclopropanation of methyl aryldiazoacetates with styrene. Rh₂(S-PTAD)₄ provides high levels of enantioinduction with ortho-substituted aryldiazoacetates. The less-established Rh₂(R-BNP)₄ plays a complementary role to Rh₂(R-DOSP)₄ and Rh₂(S-PTAD)₄ in catalyzing highly enantioselective cyclopropanation of 3-methoxy substituted aryldiazoacetates. Substitution on the styrene has only moderate influence on the asymmetric induction of the cyclopropanation.     

The application of proton nuclear magnetic resonance imaging for the in vivo characterisation of chemically induced renal lesions in rats over a prolonged time study

Renal cortical and medullary spin-lattice (T₁) relaxation times were measured at various time points over a period of 56 days following the administration of a single i.p. injection of 100 mg/kg 2-bromoethanamine hydrobromide (BEA), 200 mg/kg hexachloro-1,3-butadiene (HCBD) or 100 mg/kg puromycin aminonucleoside (PAN) to male Wistar rats. Administration of a single injection of HCBD caused a dramatic, immediate rise in the cortical T₁ values above control values, and these levels remained elevated until, by Day 28 postinjection the levels were back to control values. Administration of BEA also caused an elevation in cortical T₁ values, but in this case these values remained above control values for the rest of the study. The administration of PAN did not produce any significant increases in cortical T₁ values until 14 days postinjection. The elevated T₁ values remained above control values for the rest of the study. These increases observed in cortical T₁ values appeared to be mirrored by decreases in medullary T₁ values. Increases in cortical T₁ values were accompanied by visual changes in the NMR images and enlargement of the kidneys. The histological findings were consistent with the NMR data, confirming that morphologically the tissues did show a full recovery by Day 28 in the HCBD-treated animals. This was not the case following injection of both BEA and PAN, where necrosis was not reversible and there was no recovery of the tissues.