Salt Taste Genotype, Dietary Habits and Biomarkers of Health: No Associations in an Elderly Cohort.

A small amount of emerging research has observed variations between individual sensitivity, preference and intake of salt in the presence of single nucleotide polymorphisms (SNP) on the genes encoding salt taste receptors. Sodium intake is a significant risk factor for common diseases in elderly populations such as hypertension and cardiovascular disease; however, this does not fully explain the risk. Research into the influence of salt taste genetics on diet quality is yet to be undertaken and current research on indicators of health is limited and mixed in the direction of associations. Therefore, a secondary analysis of data from a well-characterised elderly cohort (the cross-sectional Retirement Health and Lifestyle Study, n = 536) was conducted to explore relationships between the salt taste-related SNP TRPV1-rs8065080 (assessed by Taqman genotyping assay), dietary habits and biomarkers of health. Data were analysed with standard least squares regression modelling and Tukey's HSD post hoc tests. No association was found between the TRPV1-rs8065080 genotype, sodium intake or multiple diet quality indices (assessed by food frequency questionnaire). Sodium-related markers of health including blood pressure and markers of kidney function (urinary creatinine and albumin/creatinine ratio) and general health markers, such as Body Mass Index (BMI), were also not related to TRPV1-rs8065080 genotype. To date, this study is the most comprehensive investigation conducted to determine if the TRPV1-rs8065080 genotype relates to sodium intake and health markers influenced by sodium intake. Although no significant relationships were found, these findings are an important contribution to the limited body of knowledge surround this SNP. In addition to further research across other ages and cultures, the TRPV1-rs8065080 genotype may interact with other ion channels, and so further studies are required to determine if polymorphic variations influence sodium intake, diet and health.

Optical impedance transformer for transparent conducting electrodes.

A fundamental limitation of transparent conducting electrode design is thought to be the trade-off between photonic and electronic performances. The photonic transmission property of a transparent conducting electrode, however, is not intrinsic but depends critically on the electromagnetic environment where the electrode is located. We develop the concept of optical impedance transformation, and use this concept to design nanophotonic structures that provide broadband and omnidirectional reduction of optical loss in an ultrathin transparent conducting electrode, without compromising its electrical performance.

The interaction between hepatitis B virus X protein and AIB1 oncogene is required for the activation of NFκB signal transduction.

We identified the interaction between HBV X (HBx) protein and the oncogene AIB1 (amplified in breast cancer 1). A serine/proline motif (SSPSPS) in HBx was found to be required for the interaction. Two LXD motifs [LLXX(X)L, X means any amino acids], LLRNSL and LLDQLHTLL in AIB1 were also found to be involved in the HBx-AIB1 interaction. The HBx-AIB1 interaction was important for the activation of NFκB signal transduction, the HBx mutant that did not interact with AIB1showed dramatically lower NFκB activation activity than the WT HBx. These findings contribute to the new understanding on signal transduction activation mechanisms of HBx.

Acute hepatitis as a manifestation of parvovirus B19 infection.

There are few reports in the literature of hepatitis as a manifestation of parvovirus B19 infection. We describe a case of parvovirus B19-associated acute hepatitis diagnosed based on a positive serologic test (IgM) and molecular detection of parvovirus B19 DNA in a liver biopsy specimen. Parvovirus B19 infection should be considered in the differential diagnosis of patients presenting with acute hepatitis.

Nigericin is a potent inhibitor of the early stage of vaccinia virus replication.

Poxviruses remain a significant public health concern due to their potential use as bioterrorist agents and the spread of animal borne poxviruses, such as monkeypox virus, to humans. Thus, the identification of small molecule inhibitors of poxvirus replication is warranted. Vaccinia virus is the prototypic member of the Orthopoxvirus genus, which also includes variola and monkeypox virus. In this study, we demonstrate that the carboxylic ionophore nigericin is a potent inhibitor of vaccinia virus replication in several human cell lines. In HeLa cells, we found that the 50% inhibitory concentration of nigericin against vaccinia virus was 7.9 nM, with a selectivity index of 1038. We present data demonstrating that nigericin targets vaccinia virus replication at a post-entry stage. While nigericin moderately inhibits both early vaccinia gene transcription and translation, viral DNA replication and intermediate and late gene expression are severely compromised in the presence of nigericin. Our results demonstrate that nigericin has the potential to be further developed into an effective antiviral to treat poxvirus infections.

The interaction between thymine DNA glycosylase and nuclear receptor coactivator 3 is required for the transcriptional activation of nuclear hormone receptors.

The T:G mismatch specific DNA glycosylase (TDG) is known as an important enzyme in repairing damaged DNA. Recent studies also showed that TDG interacts with a p160 protein, steroid receptor coactivator 1 or nuclear receptor coactivator 1 (SRC1), and is involved in transcriptional activation of the estrogen receptor. However, whether other members of the p160 family are also involved in TDG-interaction and signal transduction regulation remains to be seen. In this study, we employed the mammalian two-hybrid system to investigate the interaction between TDG and another member of the p160 family, nuclear receptor coactivator 3 (NCoA-3). We found that a DXXD motif from aa 294-297 within TDG was responsible for the TDG-NCoA-3 interaction, we also found that a LLXXXL motif (X means any amino acid) from aa 1029-1037 (LLRNSL) and a merged LLXXL motif (LLDQLHTLL) from aa 1053-1061 in NCoA-3 were important for the TDG-NCoA-3 interactions. Mutation of the two aspartic acids (aa 294 and 297) into two alanines in TDG significantly affected the interaction and subsequent transcriptional activation of several steroid hormone receptors including, estrogen-, androgen- and progesterone- receptors in Huh7 cells. We also identified that mutations of NCoA-3 at either leucines 1029-1030 or 1053-1054 (replaced by alanines) also reduced the interaction activity between TDG and NCoA1. These data indicated that the TDG-NCoA-3 interaction is important for broad range activation of steroid hormone nuclear receptors, and may also contribute significantly to further understanding of TDG-related nuclear receptor regulation.

In-depth characterization of the microRNA transcriptome in a leukemia progression model.

MicroRNAs (miRNAs) have been shown to play important roles in physiological as well as multiple malignant processes, including acute myeloid leukemia (AML). In an effort to gain further insight into the role of miRNAs in AML, we have applied the Illumina massively parallel sequencing platform to carry out an in-depth analysis of the miRNA transcriptome in a murine leukemia progression model. This model simulates the stepwise conversion of a myeloid progenitor cell by an engineered overexpression of the nucleoporin 98 (NUP98)-homeobox HOXD13 fusion gene (ND13), to aggressive AML inducing cells upon transduction with the oncogenic collaborator Meis1. From this data set, we identified 307 miRNA/miRNA species in the ND13 cells and 306 miRNA/miRNA species in ND13+Meis1 cells, corresponding to 223 and 219 miRNA genes. Sequence counts varied between two and 136,558, indicating a remarkable expression range between the detected miRNA species. The large number of miRNAs expressed and the nature of differential expression suggest that leukemic progression as modeled here is dictated by the repertoire of shared, but differentially expressed miRNAs. Our finding of extensive sequence variations (isomiRs) for almost all miRNA and miRNA species adds additional complexity to the miRNA transcriptome. A stringent target prediction analysis coupled with in vitro target validation revealed the potential for miRNA-mediated release of oncogenes that facilitates leukemic progression from the preleukemic to leukemia inducing state. Finally, 55 novel miRNAs species were identified in our data set, adding further complexity to the emerging world of small RNAs.

MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML.

Overexpression of wild-type MN1 is a negative prognostic factor in patients with acute myeloid leukemia (AML) with normal cytogenetics. We evaluated whether MN1 plays a functional role in leukemogenesis. We demonstrate using retroviral gene transfer and bone marrow (BM) transplantation that MN1 overexpression rapidly induces lethal AML in mice. Insertional mutagenesis and chromosomal instability were ruled out as secondary aberrations. MN1 increased resistance to all-trans retinoic acid (ATRA)-induced cell-cycle arrest and differentiation by more than 3000-fold in vitro. The differentiation block could be released by fusion of a transcriptional activator (VP16) to MN1 without affecting the ability to immortalize BM cells, suggesting that MN1 blocks differentiation by transcriptional repression. We then evaluated whether MN1 expression levels in patients with AML (excluding M3-AML) correlated with resistance to ATRA treatment in elderly patients uniformly treated within treatment protocol AMLHD98-B. Strikingly, patients with low MN1 expression who received ATRA had a significantly prolonged event-free (P = .008) and overall (P = .04) survival compared with patients with either low MN1 expression and no ATRA, or high MN1 expression with or without ATRA. MN1 is a unique oncogene in hematopoiesis that both promotes proliferation/self-renewal and blocks differentiation, and may become useful as a predictive marker in AML treatment.

Alcohol consumption increases attractiveness ratings of opposite-sex faces: a possible third route to risky sex.

AIMS: To measure the effect of moderate alcohol consumption on males' and females' attractiveness ratings of unfamiliar male and female faces. PARTICIPANTS: Eighty undergraduate volunteers were used in each of three experiments. DESIGN: Participants' ratings on a 1-7 scale was the dependent variable. A three-factor mixed design was used. For experiments 1 and 2: one within-factor, sex-of-face to be rated (male/female); two between-factors, sex-of-rater (male/female) and alcohol status of rater (0 UK units/1-6 UK units). For experiment 3, the two levels of sex-of-face were replaced by two levels of a non-face object. In experiment 1, the faces were rated for attractiveness; in experiment 2, the faces were rated for distinctiveness and in experiment 3, the non-face objects were rated for attractiveness. SETTING: Quiet, prepared corners of bars and licensed eating areas on a civic university campus. METHOD: For each experiment, 118 full-colour photographic images were presented randomly on a laptop computer screen, each remaining until a rating response was made. FINDINGS: There was a significant alcohol consumption enhancement effect only for attractiveness ratings of opposite-sex faces in experiment 1. This indicates that the opposite-sex enhancement effect is not due simply to alcohol consumption causing the use of higher points of ratings scales, in general. CONCLUSION: Since Agocha & Cooper have shown that the likelihood of intentions to engage in risky sex increases as the facial attractiveness of the potential sexual partner increases, through the opposite-sex enhancement effect we identify a new possible link between risky sex and alcohol consumption.