STUDY OBJECTIVE The aim was to investigate the effect on respiratory health of male middle tar smokers changing the tar and nicotine levels of the cigarettes they smoke for a six month period. DESIGN This was a randomised controlled trial. Middle tar smokers were randomly allocated to smoke one of three different types of cigarette (low tar, middle nicotine; middle tar, middle nicotine; and l...

The messenger RNAs of human immunodeficiency virus-1 (HIV-1) have an RNA hairpin structure, TAR, at their 5' ends that contains a six-nucleotide loop and a three-nucleotide bulge. The conformations of TAR RNA and of TAR with an arginine analog specifically bound at the binding site for the viral protein, Tat, were characterized by nuclear magnetic resonance (NMR) spectroscopy. Upon arginine bin...

A novel series of compounds, derived from [1,2,3]triazolo[4,5-d]pyrimidines with a guanidyl group or amino group-terminated side chain was designed and synthesized as HIV-1 trans-activator of transcription–trans-activation responsive region (Tat–TAR) inter action inhibitors. Their ability to inhibit Tat–TAR RNA interaction was determined by a Tatdependent HIV-1 long terminal repeat (LTR)-driven...

We present here a new set of aminoglycoside-arginine conjugates (AACs) that are either site-specific or per-arginine conjugates of paromomycin, neamine, and neomycin B as well as their structure-activity relationships. Their binding constants (KD) for TAR and RRE RNAs, measured by fluorescence anisotropy, revealed dependence on the number and location of arginines in the different aminoglycosid...

Bacterial chemoreceptors associate with the histidine kinase CheA and coupling protein CheW to form extended membrane arrays that receive and transduce environmental signals. A receptor trimers-of-dimers resides at each vertex of the hexagonal protein lattice. CheA is fully activated and regulated when it is integrated into the receptor assembly. To mimic these states in solution, we have engin...

The transactivator responsive region (TAR) present in the 5'-NTR of the HIV-1 genome represents a potential target for antiretroviral intervention and a model system for the development of specific inhibitors of RNA-protein interaction. Earlier, we have shown that an anti-TAR polyamide nucleotide analog (PNA(TAR)) conjugated to a membrane transducing (MTD) peptide, transportan, is efficiently t...

Atmospheric tar balls are particles of special morphology and composition that are fairly abundant in the plumes of biomass smoke. These particles form a specific subset of brown carbon (BrC) which has been shown to play a significant role in atmospheric shortwave absorption and, by extension, climate forcing. Here we suggest that tar balls are produced by the direct emission of liquid tar drop...

The TAR element extending from -17 to +80 in the human immunodeficiency virus long terminal repeat (HIV LTR) is required for activation of gene expression by the tat trans-activator protein. TAR RNA forms a stable stem-loop structure, and mutagenesis studies indicate that the stem structure, the primary sequence of the loop, and the bulge element are the major determinants for tat activation. R...

The taxa-area relationship (TAR) and the distance-decay relationship (DDR) both describe spatial turnover of taxa and are central patterns of biodiversity. Here, we compared TAR and DDR of bacterial communities across different marine realms and ecosystems at the global scale. To obtain reliable global estimates for both relationships, we quantified the poorly assessed effects of sequencing dep...

The pathophysiology of thrombocytopenia in the syndrome of thrombocytopenia with absent radii (TAR) is not yet understood. We examined thrombopoietin (TPO) serum levels and the in vitro reactivity of platelets to TPO in five patients affected with TAR syndrome. We found elevated TPO serum levels in all patients tested, excluding a TPO production defect as cause for thrombocytopenia in TAR syndr...