Network dynamics of eukaryotic LTR retroelements beyond phylogenetic trees

Background  

Sequencing projects have allowed diverse retroviruses and LTR retrotransposons from different eukaryotic organisms to be characterized. It is known that retroviruses and other retro-transcribing viruses evolve from LTR retrotransposons and that this whole system clusters into five families: Ty3/Gypsy, Retroviridae, Ty1/Copia, Bel/Pao and Caulimoviridae. Phylogenetic analyses usually show that these split into multiple distinct lineages but what is yet to be understood is how deep evolution occurred in this system.     

Prediction ofcis/transisomerization in proteins using PSI-BLAST profiles and secondary structure information

Background  

The majority of peptide bonds in proteins are found to occur in thetransconformation. However, for proline residues, a considerable fraction of Prolyl peptide bonds adopt thecisform. Prolinecis/transisomerization is known to play a critical role in protein folding, splicing, cell signaling and transmembrane active transport. Accurate prediction of prolinecis/transisomerization in proteins would have many important applications towards the understanding of protein structure and function.     

Expression of taste receptors in Solitary Chemosensory Cells of rodent airways

Background

Chemical irritation of airway mucosa elicits a variety of reflex responses such as coughing, apnea, and laryngeal closure. Inhaled irritants can activate either chemosensitive free nerve endings, laryngeal taste buds or solitary chemosensory cells (SCCs). The SCC population lies in the nasal respiratory epithelium, vomeronasal organ, and larynx, as well as deeper in the airway. The objective of this study is to map the distribution of SCCs within the airways and to determine the elements of the chemosensory transduction cascade expressed in these SCCs.

Methods

We utilized a combination of immunohistochemistry and molecular techniques (rtPCR and in situ hybridization) on rats and transgenic mice where the Tas1R3 or TRPM5 promoter drives expression of green fluorescent protein (GFP).

Results

Epithelial SCCs specialized for chemoreception are distributed throughout much of the respiratory tree of rodents. These cells express elements of the taste transduction cascade, including Tas1R and Tas2R receptor molecules, α-gustducin, PLCβ2 and TrpM5. The Tas2R bitter taste receptors are present throughout the entire respiratory tract. In contrast, the Tas1R sweet/umami taste receptors are expressed by numerous SCCs in the nasal cavity, but decrease in prevalence in the trachea, and are absent in the lower airways.

Conclusions

Elements of the taste transduction cascade including taste receptors are expressed by SCCs distributed throughout the airways. In the nasal cavity, SCCs, expressing Tas1R and Tas2R taste receptors, mediate detection of irritants and foreign substances which trigger trigeminally-mediated protective airway reflexes. Lower in the respiratory tract, similar chemosensory cells are not related to the trigeminal nerve but may still trigger local epithelial responses to irritants. In total, SCCs should be considered chemoreceptor cells that help in preventing damage to the respiratory tract caused by inhaled irritants and pathogens.     

The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely present in Hominidae

Background  

The parvulin-type peptidyl prolyl cis/trans isomerase Par14 is highly conserved in all metazoans. The recently identified parvulin Par17 contains an additional N-terminal domain whose occurrence and function was the focus of the present study.     

The Effect of <Emphasis Type="Italic">Tas1r3</Emphasis> Gene Polymorphism on Preference and Consumption of Sucrose and Low-Calorie Sweeteners in Interstrain Hybrid Mice of the First Filial Generation

Inter- and intra-species differences in consumption of sweet tastants formed during the evolution of vertebrates are thought to be due to polymorphism of the Tas1r3 gene encoding T1R3, a sweet taste receptor subunit. The aim of the study was to assess the effect of Tas1r3 polymorphism on nutritional behavior of laboratory mice using the first filial generation (F1) hybrids produced by crossing inbred strains with different sensitivity to sweet: 129P3/J males (129, carriers of a recessive SacD sweet taste receptor allele) and C57BL/6 females (B6, dominant SacB allele) or females of the Tas1r3 gene knockout strain, C57BL/6-Tas1r3KO (B6-Tas1r3KO). SacD/B and SacD/0 hybrids, sharing identical background genotypes, differed only by sets of Sac alleles. In a briefaccess test (BAT) or a 48-h two-bottle free choice test, the presence of the dominant SacD allele in SacD/B hybrids determined increased preference for low sucrose concentrations (1–4%) and higher concentrations of nonmetabolized sweeteners (saccharin Na, sucralose, acesulfame K). A comparison between the 129 parental strain and SacD/0 hybrids or between the B6 parental strain and hybrids from crossing B6 × B6-Tas1r3KO revealed no influence of hemizygosity of SacD or SacB on preference for sweeteners in BAT. A small decrease in sucrose and saccharin preference associated with the lack of the SacB allele was observed during long-term exposure to solutions with low concentrations of these substances. The data obtained indicate the relevance of studying the Tas1r3 polymorphism effects on preference and consumption of sweet tastants using F1 interstrain hybrids and BAT.     

Classification of rice (<Emphasis Type="Italic">Oryza sativa</Emphasis>l. japonica nipponbare) immunophilins (FKBPs,CYPs) and expression patterns under water stress

Background  

FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant and ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) superfamily, which regulate much of metabolism through a chaperone or an isomerization of proline residues during protein folding. They are collectively referred to as immunophilin (IMM), being present in almost all cellular organs. In particular, a number of IMMs relate to environmental stresses.     

Ozone uptake and its effect on photosynthetic parameters of two tobacco cultivars with contrasting ozone sensitivity

Leaf discs of the ozone tolerant tobacco (Nicotiana tabacum L.) cv. Bel B and of the ozone sensitive cv. Bel W3, were exposed to an acute ozone fumigation (300 ppb) for 3 h. We measured ozone uptake by leaves and physiological characteristics before, during and after the treatment, in order to determine if the different O₃ sensitivity was correlated to the leaf uptake. In the tolerant cv. Bel B, O₃ uptake was high during the first 2 h of ozone exposure and then decreased. In the sensitive cv. Bel W3, the rate of O₃ uptake decreased constantly during ozone fumigation. The estimated cumulative uptake over the treatment time was higher (200 ± 30 μmol m^–2) in Bel B than in Bel W3 (130 ± 12 μmol m^–2). Thus, the ozone sensitivity was not correlated with ozone uptake. Stomatal conductance and photosynthesis were significantly inhibited during the fumigation in both cultivars. However, these reductions were strong and irreversible in the cv. Bel W3, while in the cv. Bel B both parameters recovered in the post-fumigation period. Thus, ozone tolerance may be related to a sustained capacity of recovery. There was no linear correlation between ozone uptake and photosynthesis reduction, but a threshold of ozone uptake was found after which photosynthesis was substantially impaired. This threshold may or may not be reached under the same external ozone level, indicating that the AOT40 may not be a sufficiently accurate index for the detection of ozone damage in plants.     

Enhanced cell-permeant Cre protein for site-specific recombination in cultured cells

Background  

Cell-permeant Cre DNA site-specific recombinases provide an easily controlled means to regulate gene structure and function in living cells. Since recombination provides a stable and unambiguous record of protein uptake, the enzyme may also be used for quantitative studies of cis- and trans-acting factors that influence the delivery of proteins into cells.     

Nonlinear regulation enhances the phenotypic expression of trans-acting genetic polymorphisms

Background  

Genetic variation explains a considerable part of observed phenotypic variation in gene expression networks. This variation has been shown to be located both locally (cis) and distally (trans) to the genes being measured. Here we explore to which degree the phenotypic manifestation of local and distant polymorphisms is a dynamic feature of regulatory design.     

Cooperation between MEF2 and PPARγ in human intestinal β,β-carotene 15,15'-monooxygenase gene expression

Background  

Vitamin A and its derivatives, the retinoids, are essential for normal embryonic development and maintenance of cell differentiation. β, β-carotene 15,15'-monooxygenase 1 (BCMO1) catalyzes the central cleavage of β-carotene to all-trans retinal and is the key enzyme in the intestinal metabolism of carotenes to vitamin A. However, human and various rodent species show markedly different efficiencies in intestinal BCMO1-mediated carotene to retinoid conversion. The aim of this study is to identify potentially human-specific regulatory control mechanisms of BCMO1 gene expression.     

Selective cytotoxicity of Pancratistatin-related natural <Emphasis Type="Italic">Amaryllidaceae</Emphasis> alkaloids: evaluation of the activity of two new compounds

Background  

Pancratistatin (PST), a compound extracted from an Amaryllidaceae (AMD) family plant, has been shown to specifically induce apoptosis in cancer cells with no/minimal toxic effect on normal cells. A systematic synthetic approach has indicated that the minimum cytotoxic pharmacophore comprises the trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the C-ring. To further explore the structure-activity relationship of this group of compounds we have investigated the anti-cancer efficacy and specificity of two PST-related natural compounds, AMD4 and AMD5. Both of these compounds lack the polyhydroxylated lycorane element of PST instead having a methoxy-substuituted crinane skeleton.     

Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption

The taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient status. TAS1R member 3 (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. It was recently reported that deletion of TAS1R3 expression in Tas1R3 mutant mice leads to increased cortical bone mass but the underlying cellular mechanism leading to this phenotype remains unclear. Here, we independently corroborate the increased thickness of cortical bone in femurs of 20-week-old male Tas1R3 mutant mice and confirm that Tas1R3 is expressed in the bone environment. Tas1R3 is expressed in undifferentiated bone marrow stromal cells (BMSCs) in vitro and its expression is maintained during BMP2-induced osteogenic differentiation. However, levels of the bone formation marker procollagen type I N-terminal propeptide (PINP) are unchanged in the serum of 20-week-old Tas1R3 mutant mice as compared to controls. In contrast, levels of the bone resorption marker collagen type I C-telopeptide are reduced greater than 60% in Tas1R3 mutant mice. Consistent with this, Tas1R3 and its putative signaling partner Tas1R2 are expressed in primary osteoclasts and their expression levels positively correlate with differentiation status. Collectively, these findings suggest that high bone mass in Tas1R3 mutant mice is due to uncoupled bone remodeling with reduced osteoclast function and provide rationale for future experiments examining the cell-type-dependent role for TAS1R family members in nutrient sensing in postnatal bone remodeling.