Phylogenetic analysis of the alpha-globin pseudogene-4 (Hba-ps4) locus in the house mouse species complex reveals a stepwise evolution of t haplotypes [published erratum appears in Mol Biol Evol 1994 Jan;11(1):158]

A parsimony analysis was performed on restriction sites at the Hba-ps4 pseudogene locus within one of four inversions associated with mouse t haplotypes. The results suggest that all t haplotypes form a monophyletic group and that the in (17)4 inversion originated before the radiation of the Mus musculus species complex but after the divergence of the lineages leading to M. spretus, M. abbotti, and M. hortulanus. A time frame based on the evolutionary rate of mouse pseudogenes places the origin of this t haplotype inversion at 1.5 Mya, or approximately 1.5 Myr after the origin of the more proximal t complex inversion, in (17)2. The accumulated evidence indicates that complete t haplotypes have been assembled in a stepwise manner, with each of these inversions occurring on separate chromosomal lineages and at different evolutionary times. In addition, the evolutionary relationships of pseudogene sequences resulting from genetic exchange between wild-type and t haplotype alleles were examined. Analysis of sequences from the 5' and 3' sides of a putative site of recombination resulted in cladograms with different topologies. The implications for hypotheses concerning the evolutionary forces acting on t haplotypes and their rapid propagation throughout worldwide populations of mice are discussed.      

Synthesis, molecular modeling, and evaluation of nonphenolic indole analogs of mycophenolic acid

Based on the promising activity of an indole-3-carboxamide derivative, a nonphenolic analog of mycophenolic acid (MPA), we report herein the synthesis of a compound containing two important features for the activity of MPA, the ring methoxy and methyl. The synthesis was accomplished using two strategies; a method dependent on stepwise building of the hexenoate side chain followed by the indolecarboxamide ring system, and a convergent route that depended on 1,3-sigmatropic rearrangement as a key step. Docking experiments on both Chinese Hamster and Human Type-II inosine monophosphate dehydrogenase (IMPDH) showed that this compound has potential binding interactions with the NAD site. The analogs showed no activity against MCF7-S, MCF7-R, or IGR-OV1 cancer cells.     

Serum and glucocorticoid-regulated kinase Sgk1 inhibits insulin-dependent activation of phosphomannomutase 2 in transfected COS-7 cells

Serum- and glucocorticoid-regulated kinase (Sgk1) is considered to be an essential convergence point for peptide and steroid regulation of ENaC-mediated sodium transport. We tried to identify molecular partners of Sgk1 by yeast two-hybrid screening. Yeast two-hybrid screening showed a specific interaction between Sgk1 and phosphomannomutase (PMM)2, the latter of which is an enzyme involved in the regulation of glycoprotein biosynthesis. The interaction was confirmed in intact cells by coimmunoprecipitation and colocalization detected using confocal microscopy. We were then able to demonstrate that Sgk1 phosphorylated PMM2 in an in vitro assay. In addition, we found that the enzymatic activity of PMM2 is upregulated by insulin treatment and that Sgk1 completely inhibits PMM2 activity both in the absence and in the presence of insulin stimulation. These data provide evidence suggesting that Sgk1 may modulate insulin action on the cotranslational glycosylation of glycoproteins. Sgk; protein glycosylation; CDGIa     

A convenient method for the stereoselective conversion of aryl peptidyl ketones into the corresponding aryl aminomethin derivatives, a novel class of modified peptides

In this paper we describe a reductive amination procedure that can be employed in the preparation of a novel class of pseudopeptides in which a specific amide bond is replaced by a CH(Ar)NH group. The developed methodology, performed using NaBH(3)CN and TiCl(4), is characterized by the formation of diastereomeric intermediates in a relative 1:1 ratio. It provides aryl aminomethin pseudopeptides in moderate but satisfactory yields and with definite stereochemistry on the asymmetric centres next to the modified peptide bond.     

Prolonged membrane potential depolarization in cingulate pyramidal cells after digit amputation in adult rats

The anterior cingulate cortex (ACC) plays an important role in higher brain functions including learning, memory, and persistent pain. Long-term potentiation of excitatory synaptic transmission has been observed in the ACC after digit amputation, which might contribute to plastic changes associated with the phantom pain. Here we report a long-lasting membrane potential depolarization in ACC neurons of adult rats after digit amputation in vivo. Shortly after digit amputation of the hind paw, the membrane potential of intracellularly recorded ACC neurons quickly depolarized from ~-70 mV to ~-15 mV and then slowly repolarized. The duration of this amputation-induced depolarization was about 40 min. Intracellular staining revealed that these neurons were pyramidal neurons in the ACC. The depolarization is activity-dependent, since peripheral application of lidocaine significantly reduced it. Furthermore, the depolarization was significantly reduced by a NMDA receptor antagonist MK-801. Our results provide direct in vivo electrophysiological evidence that ACC pyramidal cells undergo rapid and prolonged depolarization after digit amputation, and the amputation-induced depolarization in ACC neurons might be associated with the synaptic mechanisms for phantom pain.     

Pattern of repetitive DNA of the chromosomes of Microtus agrestis

The distribution of repetitive DNA in the chromosomes of Microtus agrestis was studied with the method for demonstrating constitutive heterochromatin given by Yunis et al. (1971) and the reassociation technique described by Schnedl (1971). All autosomes can be individually recognized by means of the position of their bands. The euchromatic segment of the X1 chromosome shows the same banding pattern as the corresponding segment of X2 which consists of facultative heterochromatin. The short arms of the Y chromosome are not deeply stained with either method and therefore do not contain noticeable amounts of repetitive DNA. The relative distances between the bands remain constant during chromosome contraction in mitosis.     

Natural occurrence of microbial sulphur oxidation by long-range electron transport in the seafloor

Recently, a novel mode of sulphur oxidation was described in marine sediments, in which sulphide oxidation in deeper anoxic layers was electrically coupled to oxygen reduction at the sediment surface. Subsequent experimental evidence identified that long filamentous bacteria belonging to the family Desulfobulbaceae likely mediated the electron transport across the centimetre-scale distances. Such long-range electron transfer challenges some long-held views in microbial ecology and could have profound implications for sulphur cycling in marine sediments. But, so far, this process of electrogenic sulphur oxidation has been documented only in laboratory experiments and so its imprint on the seafloor remains unknown. Here we show that the geochemical signature of electrogenic sulphur oxidation occurs in a variety of coastal sediment environments, including a salt marsh, a seasonally hypoxic basin, and a subtidal coastal mud plain. In all cases, electrogenic sulphur oxidation was detected together with an abundance of Desulfobulbaceae filaments. Complementary laboratory experiments in intertidal sands demonstrated that mechanical disturbance by bioturbating fauna destroys the electrogenic sulphur oxidation signal. A survey of published geochemical data and 16S rRNA gene sequences identified that electrogenic sulphide oxidation is likely present in a variety of marine sediments with high sulphide generation and restricted bioturbation, such as mangrove swamps, aquaculture areas, seasonally hypoxic basins, cold sulphide seeps and possibly hydrothermal vent environments. This study shows for the first time that electrogenic sulphur oxidation occurs in a wide range of marine sediments and that bioturbation may exert a dominant control on its natural distribution.