Regulation of Androgen Receptor Activity by Transient Interactions of Its Transactivation Domain with General Transcription Regulators

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Protein import into plant mitochondria

Plant Molecular Biology -     

Self-Folding of Naked Segment 8 Genomic RNA of Influenza A Virus

Influenza A is a negative sense RNA virus that kills hundreds of thousands of humans each year. Base pairing in RNA is very favorable, but possibilities for RNA secondary structure of the influenza genomic RNA have not been investigated. This work presents the first experimentally-derived exploration of potential secondary structure in an influenza A naked (protein-free) genomic segment. Favorable folding regions are revealed by in vitro chemical structure mapping, thermodynamics, bioinformatics, and binding to isoenergetic microarrays of an entire natural sequence of the 875 nt segment 8 vRNA and of a smaller fragment. Segment 8 has thermodynamically stable and evolutionarily conserved RNA structure and encodes essential viral proteins NEP and NS1. This suggests that vRNA self-folding may generate helixes and loops that are important at one or more stages of the influenza life cycle.     

DNA Copy Number Aberrations,and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes

Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status. Seventy formalin-fixed, paraffin embedded penile squamous cell carcinomas were centrally reviewed by expert uropathologists. DNA was extracted from micro-dissected samples, subjected to PCR-based human papillomavirus assessment and genotyping (INNO-LiPA human papillomavirus Genotyping Extra Assay) and microarray-based comparative genomic hybridization using a 32K Bacterial Artificial Chromosome array platform. Sixty-four samples yielded interpretable results. Recurrent gains were observed in chromosomes 1p13.3-q44 (88%), 3p12.3-q29 (86%), 5p15.33-p11 (67%) and 8p12-q24.3 (84%). Amplifications of 5p15.33-p11 and 11p14.1-p12 were found in seven (11%) and four (6%) cases, respectively. Losses were observed in chromosomes 2q33-q37.3 (86%), 3p26.3-q11.1 (83%) and 11q12.2-q25 (81%). Although many losses and gains were similar throughout the cohort, there were small significant differences observed at specific loci, between human papillomavirus positive and negative tumors, between tumor types, and tumor grade and nodal status. These results demonstrate that despite the diversity of genetic aberrations in penile squamous cell carcinomas, there are significant correlations between the clinico-pathological data and the genetic changes that may play a role in disease natural history and progression and highlight potential driver genes, which may feature in molecular pathways for existing therapeutic agents.     

Amylase Activities in Attached and Excised Cotyledons and in Embryonic Axes of Pisum sativum L.

Amylase activity increased in attached cotyledons of peas, Pisumsativum L. var. Bördi, only during imbibition and remainedalmost constant up to 96 h after germination, but in excisedcotyledons the activity increased slightly at first then markedly.In contrast, the content of the reducing sugars was higher inattached cotyledons than in excised ones. A similar inverserelationship has been found between the concentration of reducingsugars in axes (both attached and excised) and amylase activity. The leakage from intact seeds contained more reducing sugarsthan the leakage from excised cotyledons, whereas the amountof proteins released from the cotyledons was four times greaterduring imbibition. This increase in amylase activity in excisedcotyledons is not thought to be the result of axis excision,but to be the result of the leakage of sugars from the cotyledonsduring incubation. These results suggest that the concentration of reducing sugarsmay be a factor that regulates amylase activity in vivo in boththe cotyledons and axis during the germination of pea seeds. (Received August 4, 1982; Accepted December 14, 1982)     

Gibberellin-like activity in pea seedlings during growth under red,blue and white light

The influence of blue, red and white light and gibberellic acid (GA₃) on gibberellin-like activity in tissue extracts of leaves, stems and roots was investigated during growth of pea seedlings (Pisum salivum L. cv. Bördi). Higher GA-like activity was found in leaves and stems of pea plants that were growing in blue light than in those under red or white light. Patterns of change of activity were different in leaves, stems and roots, and in GA₃-treated plants.     

Influence of Various Factors on the Survival of Lactobacillus leichmannii during Freezing and Thawing

S ummary : The influence of the age and activity of bacteria, their concentration in the protective medium, the pH value of the medium, the temperature of thawing, and the time of storage on the survival of L. leichmannii during freezing and thawing has been investigated.     

Role of NO and COX pathways in mediation of adenosine A1 receptor-induced renal vasoconstriction

The mechanism of adenosine A1 receptor-induced intrarenal vasoconstriction is unclear; it depends on sodium intake and may be mediated by changing the intrarenal activity of the nitric oxide (NO) and/or cyclooxygenase (COX) pathway of arachidonic acid metabolism. The effects of 2-chloro-N(6)-cyclopentyl-adenosine (CCPA), a selective A1 receptor agonist, on renal hemodynamics were examined in anesthetized rats maintained on high sodium (HS) or low sodium (LS) diet. Total renal (i.e., cortical) blood flow (RBF) as well as superficial cortical (CBF), outer medullary (OMBF), and inner medullary (IMBF) flows were determined by laser-Doppler. In HS rats, suprarenal aortic infusions of 8-40 nmol/kg/hr CCPA decreased IMBF (15%) and other perfusion indices (22%-27%); in LS rats, IMBF increased 3% (insignificant) and other indices decreased 13%-24%. In LS rats, pretreatment with N-nitro-L-arginine methyl ester prevented the A1 receptor-mediated decrease in RBF and CBF but not OMBF; the response in IMBF was not altered. Pretreatment with indomethacin prevented the decreases in RBF, CBF, and OMBF and did not change the response of IMBF. Thus, within the cortex the vasoconstriction that follows A1 receptor activation results both from inhibition of NO synthesis and from stimulation of vasoconstrictor products of the COX pathway. In the outer medulla, the latter products seem exclusively responsible for CCPA-induced vasoconstriction. The observation that in LS rats IMBF was not affected by stimulation of adenosine A1 receptors suggests that limiting salt intake may help protect medullary perfusion against vasoconstrictor stimuli which have the potential to disturb long-term control of arterial pressure.     

Effect of base modifications on structure, thermodynamic stability, and gene silencing activity of short interfering RNA

A series of nucleobase-modified siRNA duplexes containing "rare" nucleosides, 2-thiouridine (s(2)U), pseudouridine (Psi), and dihydrouridine (D), were evaluated for their thermodynamic stability and gene silencing activity. The duplexes with modified units at terminal positions exhibited similar stability as the nonmodified reference. Introduction of the s(2)U or Psi units into the central part of the antisense strand resulted in duplexes with higher melting temperatures (Tm). In contrary, D unit similarly like wobble base pair led to the less stable duplexes (DeltaTm 3.9 and 6.6 degrees C, respectively). Gene-silencing activity of siRNA duplexes directed toward enhanced green fluorescent protein or beta-site APP cleaving enzyme was tested in a dual fluorescence assay. The duplexes with s(2)U and Psi units at their 3'-ends and with a D unit at their 5'-ends (with respect to the guide strands) were the most potent gene expression inhibitors. Duplexes with s(2)U and Psi units at their 5'-ends were by 50% less active than the nonmodified counterpart. Those containing a D unit or wobble base pair in the central domain had the lowest Tm, disturbed the A-type helical structure, and had more than three times lower activity than their nonmodified congener. Activity of siRNA containing the wobble base pair could be rescued by placing the thio-nucleoside at the position 3'-adjacent to the mutation site. Thermally stable siRNA molecules containing several s(2)U units in the antisense strand were biologically as potent as their native counterparts. The present results provide a new chemical tool for modulation of siRNA gene-silencing activity.