Fecal Selenium Excretion Is Regulated by Dietary Selenium Intake

Whole-body selenium is regulated by excretion of the element. Reports of studies carried out using isotopic tracers have led to the conclusion that urinary selenium excretion is regulated by selenium intake but that fecal excretion is not. Because of the limitations of tracer studies, we measured urinary and fecal selenium excretion by mice with selenium intakes in the form of sodium selenite ranging from deficient to almost toxic. Tissue and whole-body selenium concentrations increased sharply between deficient and adequate selenium intakes, reflecting tissue accumulation of selenium in the form of selenoproteins. Once the requirement for selenium had been satisfied, a 31-fold further increase in intake resulted in less than doubling of tissue and whole-body selenium, demonstrating the effectiveness of selenium excretion by the mouse. Urinary selenium excretion increased with increases in dietary selenium intake. Fecal selenium excretion, which was 20 to 30?% of the selenium excreted in the physiological range, responded to moderately high selenium intake but did not increase further when selenium intake was increased to even higher levels. Thus, fecal selenium excretion contributes to regulation of whole-body selenium at physiological selenium intakes. The pattern of its response to the full spectrum of selenium intakes was different from the urinary excretion response, suggesting that the mechanisms of fecal and urinary routes of excretion are different.     

Fnr (EtrA) acts as a fine-tuning regulator of anaerobic metabolism in <Emphasis Type="Italic">Shewanella oneidensis</Emphasis>MR-1

Background  

EtrA in Shewanella oneidensis MR-1, a model organism for study of adaptation to varied redox niches, shares 73.6% and 50.8% amino acid sequence identity with the oxygen-sensing regulators Fnr in E. coli and Anr in Pseudomonas aeruginosa, respectively; however, its regulatory role of anaerobic metabolism in Shewanella spp. is complex and not well understood.     

EGF-stimulation activates the nuclear localization signal of SHP-1

Protein tyrosine phosphatase SHP-1 plays a critical role in the regulation of a variety of intracellular signaling pathways. SHP-1 is predominantly expressed in the cells of hematopoietic origin, and is recognized as a negative regulator of lymphocyte development and activation. SHP-1 consists of two Src homology 2 (SH2) domains and one protein tyrosine phosphatase (PTP) domain followed by a highly basic C-terminal tail containing tyrosyl phosphorylation sites. It is unclear how the C-terminal tail regulates SHP-1 function. We report the examination of the subcellular localization of a variety of truncated or mutated SHP-1 proteins fused with enhanced green fluorescent protein (EGFP) protein at either the N-terminal or the C-terminal end in different cell lines. Our data demonstrate that a nuclear localization signal (NLS) is located in the C-terminal tail of SHP-1 and the signal is primarily defined by three amino-acid residues (KRK) at the C-terminus. This signal is generally blocked in the native protein and can be exposed by fusing EGFP at the appropriate position or by domain truncation. We have also revealed that this NLS of SHP-1 is triggered by epidermal growth factor (EGF) stimulation and mediates translocation of SHP-1 from the cytosol to the nucleus in COS7 cell lines. These results not only demonstrate the importance of the C-terminal tail of SHP-1 in the regulation of nuclear localization, but also provide insights into its role in SHP-1-involved signal transduction pathways.     

Production of Selenoprotein P (Sepp1) by Hepatocytes Is Central to Selenium Homeostasis

Sepp1 is a widely expressed extracellular protein that in humans and mice contains 10 selenocysteine residues in its primary structure. Extra-hepatic tissues take up plasma Sepp1 for its selenium via apolipoprotein E receptor-2 (apoER2)-mediated endocytosis. The role of Sepp1 in the transport of selenium from liver, a rich source of the element, to peripheral tissues was studied using mice with selective deletion of Sepp1 in hepatocytes (Sepp1^c/c/alb-cre^+/− mice). Deletion of Sepp1 in hepatocytes lowered plasma Sepp1 concentration to 10% of that in Sepp1^c/c mice (controls) and increased urinary selenium excretion, decreasing whole-body and tissue selenium concentrations. Under selenium-deficient conditions, Sepp1^c/c/alb-cre^+/− mice accumulated selenium in the liver at the expense of extra-hepatic tissues, severely worsening clinical manifestations of dietary selenium deficiency. These findings are consistent with there being competition for metabolically available hepatocyte selenium between the synthesis of selenoproteins and the synthesis of selenium excretory metabolites. In addition, selenium deficiency down-regulated the mRNA of the most abundant hepatic selenoprotein, glutathione peroxidase-1 (Gpx1), to 15% of the selenium-replete value, while reducing Sepp1 mRNA, the most abundant hepatic selenoprotein mRNA, only to 61%. This strongly suggests that Sepp1 synthesis is favored in the liver over Gpx1 synthesis when selenium supply is limited, directing hepatocyte selenium to peripheral tissues in selenium deficiency. We conclude that production of Sepp1 by hepatocytes is central to selenium homeostasis in the organism because it promotes retention of selenium in the body and effects selenium distribution from the liver to extra-hepatic tissues, especially under selenium-deficient conditions.     

The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes

Background  

Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or glutamine. Carbamoylphosphate synthetase (CPS), ornithine aminotransferase (OAT), argininosuccinate synthetase (ASS), arginase-1 (ARG1), arginase-2 (ARG2), and nitric-oxide synthase (NOS) were visualized by semiquantitative immunohistochemistry in 89 small-intestinal specimens.     

Phylogenetic incongruence among oncogenic genital alpha human papillomaviruses

The human papillomaviruses (HPVs) have long been thought to follow a monophyletic pattern of evolution with little if any evidence for recombination between genomes. On the basis of this model, both oncogenicity and tissue tropism appear to have evolved once. Still, no systematic statistical analyses have shown whether monophyly is the rule across all HPV open reading frames (ORFs). We conducted a taxonomic analysis of 59 mucosal/genital HPVs using whole-genome and sliding-window similarity measures; maximum-parsimony, neighbor-joining, and Bayesian phylogenetic analyses; and localized incongruence length difference (LILD) analyses. The algorithm for the LILD analyses localized incongruence by calculating the tree length differences between constrained and unconstrained nodes in a total-evidence tree across all HPV ORFs. The process allows statistical evaluation of every ORF/node pair in the total-evidence tree. The most significant incongruence was observed at the putative high-risk (i.e., cancer-associated) node, the common oncogenic ancestor for alpha HPV species 9 (e.g., HPV type 16 [HPV16]), 11, 7 (e.g., HPV18), 5, and 6. Although these groups share early-gene homology, including high degrees of similarity among E6 and E7, groups 9 and 11 diverge from groups 7, 5, and 6 with respect to L2 and L1. The HPV species groups primarily associated with cervical and anogenital cancers appear to follow two distinct evolutionary paths, one conferred by the early genes and another by the late genes. The incongruence in the genital HPV phylogeny could have occurred from an early recombination event, an ecological niche change, and/or asymmetric genome convergence driven by intense selection. These data indicate that the phylogeny of the oncogenic HPVs is complex and that their evolution may not be monophyletic across all genes.     

Membrane resistance change of the frog taste cells in response to water and Nacl

The electrical properties of the frog taste cells during gustatory stimulations with distilled water and varying concentrations of NaCl were studied with intracellular microelectrodes. Under the Ringer adaptation of the tongue, two types of taste cells were distinguished by the gustatory stimuli. One type, termed NaCl-sensitive (NS) cells, responded to water with hyperpolarizations and responded to concentrated NaCl with depolarizations. In contrast, the other type of cells, termed water-sensitive (WS) cells, responded to water depolarizations and responded to concentrated NaCl with hyperpolarizations. The membrane resistance of both taste cell types increased during the hyperpolarizing receptor potentials and decreased during the depolarizing receptor potentials, Reversal potentials for the depolarizing and hyperpolarizing responses in each cell type were a few millivolts positive above the zero membrane potential. When the tongue was adapted with Na-free Ringer solution for 30 min, the amplitude of the depolarizing responses in the NS cells reduced to 50% of the control value under normal Ringer adaptation. On the basis of the present results, it is concluded (a) that the depolarizing responses of the NS and WS cells under the Ringer adaptation are produced by the permeability increase in some ions, mainly Na+ ions across the taste cell membranes, and (b) that the hyperpolarizing responses of both types of taste cells are produced by a decrease in the cell membrane permeability to some ions, probably Na+ ions, which is slightly enhanced during the Ringer adaptation.     

Satellite DNA repeat sequence variation is low in three species of burying beetles in the genus Nicrophorus (Coleoptera: Silphidae)

Three satellite DNA families were identified in three species of burying beetles, Nicrophorus orbicollis, N. marginatus, and N. americanus. Southern hybridization and nucleotide sequence analysis of individual randomly cloned repeats shows that these satellite DNA families are highly abundant in the genome, are composed of unique repeats, and are species-specific. The repeats do not have identifiable core elements or substructures that are similar in all three families, and most interspecific sequence similarity is confined to homopolymeric runs of A and T. Satellite DNA from N. marginatus and N. americanus show single-base-pair indels among repeats, but single-nucleotide substitutions characterize most of the repeat variability. Although the repeat units are of similar lengths (342, 350, and 354 bp) and A + T composition (65%, 71%, and 71%, respectively), the average nucleotide divergence among sequenced repeats is very low (0.18%, 1.22%, and 0.71%, respectively). Transition/transversion ratios from the consensus sequence are 0.20, 0.69, and 0.70, respectively.