The effect of host structure on the selectivity and mechanism of supramolecular catalysis of Prins cyclizations.

The effect of host structure on the selectivity and mechanism of intramolecular Prins reactions is evaluated using K12Ga4L6 tetrahedral catalysts. The host structure was varied by modifying the structure of the chelating moieties and the size of the aromatic spacers. While variation in chelator substituents was generally observed to affect changes in rate but not selectivity, changing the host spacer afforded differences in efficiency and product diastereoselectivity. An extremely high number of turnovers (up to 840) was observed. Maximum rate accelerations were measured to be on the order of 105, which numbers among the largest magnitudes of transition state stabilization measured with a synthetic host-catalyst. Host/guest size effects were observed to play an important role in host-mediated enantioselectivity

The unusual dynamics of parasite actin result from isodesmic polymerization

Previous reports have indicated that parasite actins are short and inherently unstable, despite being required for motility. Here, we re-examine the polymerization properties of actin in Toxoplasma gondii (TgACTI), unexpectedly finding that it exhibits isodesmic polymerization in contrast to the conventional nucleation-elongation process of all previously studied actins from both eukaryotes and bacteria. TgACTI polymerization kinetics lacks both a lag phase and critical concentration, normally characteristic of actins. Unique among actins, the kinetics of assembly can be fit with a single set of rate constants for all subunit interactions, without need for separate nucleation and elongation rates. This isodesmic model accurately predicts the assembly, disassembly, and the size distribution of TgACTI filaments in vitro, providing a mechanistic explanation for actin dynamics in vivo. Our findings expand the repertoire of mechanisms by which actin polymerization is governed and offer clues about the evolution of self-assembling, stabilized protein polymers

A New 24 micron Phase Curve for upsilon Andromedae b

We report the detection of 24 micron variations from the planet-hosting upsilon Andromedae system consistent with the orbital periodicity of the system's innermost planet, upsilon And b. We find a peak-to-valley phase curve amplitude of 0.00130 times the mean system flux. Using a simple model with two hemispheres of constant surface brightness and assuming a planetary radius of 1.3 Jupiter radii gives a planetary temperature contrast of >900 K and an orbital inclination of >28 degrees. We further report the largest phase offset yet observed for an extrasolar planet: the flux maximum occurs ~80 degrees before phase 0.5. Such a large phase offset is difficult to reconcile with most current atmospheric circulation models. We improve on earlier observations of this system in several important ways: (1) observations of a flux calibrator star demonstrate the MIPS detector is stable to 10^-4 on long timescales, (2) we note that the background light varies systematically due to spacecraft operations, precluding use of this background as a flux calibrator (stellar flux measured above the background is not similarly affected), and (3) we calibrate for flux variability correlated with motion of the star on the MIPS detector. A reanalysis of our earlier observations of this system is consistent with our new result.Comment: Submitted to ApJ. 15 pages, 6 figures, 4 table

Guidance and Ethical Considerations for Undertaking Transgender Health Research and Institutional Review Boards Adjudicating this Research

The purpose of this review is to create a set of provisional criteria for Institutional Review Boards (IRBs) to refer to when assessing the ethical orientation of transgender health research proposals. We began by searching for literature on this topic using databases and the reference lists of key articles, resulting in a preliminary set of criteria. We then collaborated to develop the following nine guidelines: (1) Whenever possible, research should be grounded, from inception to dissemination, in a meaningful collaboration with community stakeholders; (2) language and framing of transgender health research should be non-stigmatizing; (3) research should be disseminated back to the community; (4) the diversity of the transgender and gender diverse (TGGD) community should be accurately reflected and sensitively reflected; (5) informed consent must be meaningful, without coercion or undue influence; (6) the protection of participant confidentiality should be paramount; (7) alternative consent procedures should be considered for TGGD minors; (8) research should align with current professional standards that refute conversion, reorientation, or reparative therapy; and (9) IRBs should guard against the temptation to avoid, limit, or delay research on this subject

Carma CO observations of three extremely metal-poor, star-forming galaxies

We present sensitive CO (J = 1 0) emission line observations of the three metal-poor dwarf irregular galaxies Leo P (Z ∼ 3% Zo), Sextans A (Z ∼ 7.5% Zo), and Sextans B (Z ∼ 7.5% Zo), all obtained with the Combined Array for Millimeter-wave Astronomy interferometer. While no CO emission was detected, the proximity of the three systems allows us to place very stringent (4σ) upper limits on the CO luminosity (LCO) in these metal-poor galaxies. We find the CO luminosities to be LCO < 2900 K km s-1 pc2 for Leo P, LCO < 12,400 K km s-1 pc2 for Sextans A, and LCO < 9700 K km s-1 pc2 for Sextans B. Comparison of our results with recent observational estimates of the factor for converting between LCO and the mass of molecular hydrogen, as well as theoretical models, provides further evidence that either the CO-to-H2 conversion factor increases sharply as metallicity decreases, or that stars are forming in these three galaxies very efficiently, requiring little molecular hydroge

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

Advancing Research on the Complex Interrelations Between Atrial Fibrillation and Heart Failure A Report From a US National Heart, Lung, and Blood Institute Virtual Workshop

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF