SUVH1, a Su(var)3-9 family member, promotes the expression of genes targeted by DNA methylation.

Transposable elements are found throughout the genomes of all organisms. Repressive marks such as DNA methylation and histone H3 lysine 9 (H3K9) methylation silence these elements and maintain genome integrity. However, how silencing mechanisms are themselves regulated to avoid the silencing of genes remains unclear. Here, an anti-silencing factor was identified using a forward genetic screen on a reporter line that harbors a LUCIFERASE (LUC) gene driven by a promoter that undergoes DNA methylation. SUVH1, a Su(var)3-9 homolog, was identified as a factor promoting the expression of the LUC gene. Treatment with a cytosine methylation inhibitor completely suppressed the LUC expression defects of suvh1, indicating that SUVH1 is dispensable for LUC expression in the absence of DNA methylation. SUVH1 also promotes the expression of several endogenous genes with promoter DNA methylation. However, the suvh1 mutation did not alter DNA methylation levels at the LUC transgene or on a genome-wide scale; thus, SUVH1 functions downstream of DNA methylation. Histone H3 lysine 4 (H3K4) trimethylation was reduced in suvh1; in contrast, H3K9 methylation levels remained unchanged. This work has uncovered a novel, anti-silencing function for a member of the Su(var)3-9 family that has previously been associated with silencing through H3K9 methylation

Uniform continuity over locally compact quantum groups

We define, for a locally compact quantum group $G$ in the sense of Kustermans--Vaes, the space of $LUC(G)$ of left uniformly continuous elements in $L^\infty(G)$. This definition covers both the usual left uniformly continuous functions on a locally compact group and Granirer's uniformly continuous functionals on the Fourier algebra. We show that $LUC(G)$ is an operator system containing the $C^*$-algebra $C_0(G)$ and contained in its multiplier algebra $M(C_0(G))$. We use this to partially answer an open problem by Bedos--Tuset: if $G$ is co-amenable, then the existence of a left invariant mean on $M(C_0(G))$ is sufficient for $G$ to be amenable. Furthermore, we study the space $WAP(G)$ of weakly almost periodic elements of $L^\infty(G)$: it is a closed operator system in $L^\infty(G)$ containing $C_0(G)$ and--for co-amenable $G$--contained in $LUC(G)$. Finally, we show that--under certain conditions, which are always satisfied if $G$ is a group--the operator system $LUC(G)$ is a $C^*$-algebra.Comment: 22 pages; some nip and tuc

Sexual Differentiation of Circadian Clock Function in the Adrenal Gland

Sex differences in glucocorticoid production are associated with increased responsiveness of the adrenal gland in females. However, the adrenal-intrinsic mechanisms that establish sexual dimorphic function remain ill defined. Glucocorticoid production is gated at the molecular level by the circadian clock, which may contribute to sexual dimorphic adrenal function. Here we examine sex differences in the adrenal gland using an optical reporter of circadian clock function. Adrenal glands were cultured from male and female Period2::Luciferase (PER2::LUC) mice to assess clock function in vitro in real time. We confirm that there is a pronounced sex difference in the intrinsic capacity to sustain PER2::LUC rhythms in vitro, with higher amplitude rhythms in adrenal glands collected from males than from females. Changes in adrenal PER2::LUC rhythms over the reproductive life span implicate T as an important factor in driving sex differences in adrenal clock function. By directly manipulating hormone levels in adult mice in vivo, we demonstrate that T increases the amplitude of PER2::LUC rhythms in adrenal glands of both male and female mice. In contrast, we find little evidence that ovarian hormones modify adrenal clock function. Lastly, we find that T in vitro can increase the amplitude of PER2::LUC rhythms in male adrenals but not female adrenals, which suggests the existence of sex differences in the mechanisms of T action in vivo. Collectively these results reveal that activational effects of T alter circadian timekeeping in the adrenal gland, which may have implications for sex differences in stress reactivity and stress-related disorders

Gravity’s rainbow, domination and freedom [Luc Herman and Steven Weisenburger, Athens: University of Georgia Press, 2013]

Review of Luc Herman and Steven Weisenburger, Gravity’s Rainbow, Domination, and Freedom (Athens: University of Georgia Press, 2013

Novel locally active estrogens accelerate cutaneous wound healing-part 2

Estrogen deprivation is associated with delayed healing, while estrogen replacement therapy (ERT) accelerates acute wound healing and protects against development of chronic wounds. However, current estrogenic molecules have undesired systemic effects, thus the aim of our studies is to generate new molecules for topic administration that are devoid of systemic effects. Following a preliminary study, the new 17β-estradiol derivatives 1 were synthesized. The estrogenic activity of these novel compounds was evaluated in vitro using the cell line ERE-Luc B17 stably transfected with an ERE-Luc reporter. Among the 17β-estradiol derivatives synthesized, compounds 1e and 1f showed the highest transactivation potency and were therefore selected for the study of their systemic estrogenic activity. The study of these compounds in the ERE-Luc mouse model demonstrated that both compounds lack systemic effects when administered in the wound area. Furthermore, wound-healing experiments showed that 1e displays a significant regenerative and anti-inflammatory activity. It is therefore confirmed that this class of compounds are suitable for topical administration and have a clear beneficial effect on wound healing

Liposome immunoassay based on bio luminescent detection and its application to on-chip analysis

Luc-encapsulated liposomes were employed to develop on-chip immunoassays. Straight-channel chips were better than microbead for V-cup chips to immobilize several antibodies. Straight-channel chip that has PDMS flat substrate and wider channel (1000 μm) was optimum for this assay. To detect high BL intensity, fast flow rate (300 μl/min) was better than slower flow rate because channel was filled up with substrate quickly. However, substrate volume and lysis buffer didn't affect the detecttion high BL intensity. This implies that a sufficient amount of substrate was delivered to Luc in the liposomes. The LOD of CRP in this assay was 10 ng/mL