Multiple prebiotic metals mediate translation.

Today, Mg2+ is an essential cofactor with diverse structural and functional roles in life's oldest macromolecular machine, the translation system. We tested whether ancient Earth conditions (low O2, high Fe2+, and high Mn2+) can revert the ribosome to a functional ancestral state. First, SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) was used to compare the effect of Mg2+, Fe2+, and Mn2+ on the tertiary structure of rRNA. Then, we used in vitro translation reactions to test whether Fe2+ or Mn2+ could mediate protein production, and quantified ribosomal metal content. We found that (i) Mg2+, Fe2+, and Mn2+ had strikingly similar effects on rRNA folding; (ii) Fe2+ and Mn2+ can replace Mg2+ as the dominant divalent cation during translation of mRNA to functional protein; and (iii) Fe and Mn associate extensively with the ribosome. Given that the translation system originated and matured when Fe2+ and Mn2+ were abundant, these findings suggest that Fe2+ and Mn2+ played a role in early ribosomal evolution

VEZF1 elements mediate protection from DNA methylation

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat

A CRY-BIC negative-feedback circuitry regulating blue light sensitivity of Arabidopsis.

Cryptochromes are blue light receptors that regulate various light responses in plants. Arabidopsis cryptochrome 1 (CRY1) and cryptochrome 2 (CRY2) mediate blue light inhibition of hypocotyl elongation and long-day (LD) promotion of floral initiation. It has been reported recently that two negative regulators of Arabidopsis cryptochromes, Blue light Inhibitors of Cryptochromes 1 and 2 (BIC1 and BIC2), inhibit cryptochrome function by blocking blue light-dependent cryptochrome dimerization. However, it remained unclear how cryptochromes regulate the BIC gene activity. Here we show that cryptochromes mediate light activation of transcription of the BIC genes, by suppressing the activity of CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), resulting in activation of the transcription activator ELONGATED HYPOCOTYL 5 (HY5) that is associated with chromatins of the BIC promoters. These results demonstrate a CRY-BIC negative-feedback circuitry that regulates the activity of each other. Surprisingly, phytochromes also mediate light activation of BIC transcription, suggesting a novel photoreceptor co-action mechanism to sustain blue light sensitivity of plants under the broad spectra of solar radiation in nature

Mediating Multiculturally: Culture and the Ethical Mediator

This commentary on mediating multiculturally in a chapter of Mediation Ethics (edited by Ellen Waldman) suggests there are times when mediators should not mediate, because of their own ethical commitments. Commenting on a hypothetical divorce scenario (of Ziba, a 17 year old from her 44 year old husband, with two children aged 3 and 2, where the parties claim to want Shari’a principles to apply), the author (Carrie Menkel-Meadow) suggests that she would not mediate a case which might violate formal laws (American marriage and divorce laws) or infringe on rights that one of the parties might not be fully aware of. A variety of sources of ethics, including formal law, legal and mediation ethical rules, and personal ethical commitments may structure how mediators choose whether to take a case, educate the parties about their rights, make a referral, or how to mediate if complex (and different for each of the parties and/or the mediator) legal, moral, religious and cultural values are at stake. The chapter contains contrasting views expressed by two different mediators, with summary and commentary by the book’s editor

Pathogen Response Genes Mediate Caenorhabditis elegans Innate Immunity

Innate immunity is crucial in the response and defense against pathogens for invertebrates and vertebrates alike. The soil nematode Caenorhabditis elegans is a useful model to study the eukaryotic innate immune response to microbial pathogenesis. Prior research indicates that the protein receptor FSHR-1 plays an important role in the innate recognition of intestinal infection due to pathogen consumption. Determining what genes are controlled by FSHR-1 may uncover an unknown pathway that could increase not only the comprehension of the C. elegans immune system but also innate immunity generally. To characterize the function of FSHR-1, four candidate pathogen response genes that appear to be regulated by FSHR-1 were evaluated in worms infected with Pseudomonas aeruginosa. Although intestine specific RNA interference of these four genes did not show immunity phenotypes, quantitative PCR suggests that FSHR-1 regulates the basal and/or infection-induced expression of three of the four genes. To explore this FSHR-1-dependent transcriptional induction, fluorescent transgenic reporters were constructed for the three candidate FSHR-1 target genes. The spatial expression of one putative pathogen response gene was characterized in transgenic worms under both control and pathogenic conditions. RNA interference was performed to assess the FSHR-1 dependency of this expression pattern

The role of deliberate practice in expertise: Necessary but not sufficient

The paper discusses recent data on deliberate practice in chess, and argues that other factors mediate expertise in chess

Is the vagus nerve our neural connectome?

What are the implications of the vagus nerve being able to mediate the time-dependent plasticity of an array of sensorimotor networks

Structure of the CLC-1 chloride channel from Homo sapiens.

CLC channels mediate passive Cl- conduction, while CLC transporters mediate active Cl- transport coupled to H+ transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl- conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl- at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl- affinity distinguish CLC channels and transporters

Natural scene statistics mediate the perception of image complexity

Humans are sensitive to complexity and regularity in patterns. The subjective perception of pattern complexity is correlated to algorithmic (Kolmogorov-Chaitin) complexity as defined in computer science, but also to the frequency of naturally occurring patterns. However, the possible mediational role of natural frequencies in the perception of algorithmic complexity remains unclear. Here we reanalyze Hsu et al. (2010) through a mediational analysis, and complement their results in a new experiment. We conclude that human perception of complexity seems partly shaped by natural scenes statistics, thereby establishing a link between the perception of complexity and the effect of natural scene statistics

Yin and yang of interleukin-17 in host immunity to infection [version 1; referees: 2 approved]

The interleukin-17 (IL-17) family cytokines, such as IL-17A and IL-17F, play important protective roles in host immune response to a variety of infections such as bacterial, fungal, parasitic, and viral. The IL-17R signaling and downstream pathways mediate induction of proinflammatory molecules which participate in control of these pathogens. However, the production of IL-17 can also mediate pathology and inflammation associated with infections. In this review, we will discuss the yin-and-yang roles of IL-17 in host immunity to pathogens