Dissecting the functional role of polyketide synthases in Dictyostelium discoideum

Dictyostelium discoideum exhibits the largest repository of polyketide synthase (PKS) proteins of all known genomes. However, the functional relevance of these proteins in the biology of this organism remains largely obscure. On the basis of computational, biochemical, and gene expression studies, we propose that the multifunctional Dictyostelium PKS (DiPKS) protein DiPKS1 could be involved in the biosynthesis of the differentiation regulating factor 4-methyl-5-pentylbenzene-1,3-diol (MPBD). Our cell-free reconstitution studies of a novel acyl carrier protein Type III PKS didomain from DiPKS1 revealed a crucial role of protein-protein interactions in determining the final biosynthetic product. Whereas the Type III PKS domain by itself primarily produces acyl pyrones, the presence of the interacting acyl carrier protein domain modulates the catalytic activity to produce the alkyl resorcinol scaffold of MPBD. Furthermore, we have characterized an O-methyltransferase (OMT12) from Dictyostelium with the capability to modify this resorcinol ring to synthesize a variant of MPBD. We propose that such a modification in vivo could in fact provide subtle variations in biological function and specificity. In addition, we have performed systematic computational analysis of 45 multidomain PKSs, which revealed several unique features in DiPKS proteins. Our studies provide a new perspective in understanding mechanisms by which metabolic diversity could be generated by combining existing functional scaffolds

Acoustic Power Absorption and its Relation with Vector Magnetic Field of a Sunspot

The distribution of acoustic power over sunspots shows an enhanced absorption near the umbra--penumbra boundary. Earlier studies revealed that the region of enhanced absorption coincides with the region of strongest transverse potential field. The aim of this paper is to (i) utilize the high-resolution vector magnetograms derived using Hinode SOT/SP observations and study the relationship between the vector magnetic field and power absorption and (ii) study the variation of power absorption in sunspot penumbrae due to the presence of spine-like radial structures. It is found that (i) both potential and observed transverse fields peak at a similar radial distance from the center of the sunspot, and (ii) the magnitude of the transverse field, derived from Hinode observations, is much larger than the potential transverse field derived from SOHO/MDI longitudinal field observations. In the penumbra, the radial structures called spines (intra-spines) have stronger (weaker) field strength and are more vertical (horizontal). The absorption of acoustic power in the spine and intra-spine shows different behaviour with the absorption being larger in the spine as compared to the intra-spine.Comment: 18 pages, 7 figures, In Press Solar Physics, Topical Issue on Helio-and-Astroseismolog

Magnetic Field Structures in a Facular Region Observed by THEMIS and Hinode

The main objective of this paper is to build and compare vector magnetic maps obtained by two spectral polarimeters, i.e. THEMIS/MTR and Hinode SOT/SP, using two inversion codes (UNNOFIT and MELANIE) based on the Milne-Eddington solar atmosphere model. To this end, we used observations of a facular region within active region NOAA 10996 on 23 May 2008, and found consistent results concerning the field strength, azimuth and inclination distributions. Because SOT/SP is free from the seeing effect and has better spatial resolution, we were able to resolve small magnetic polarities with sizes of 1" to 2", and we could detect strong horizontal magnetic fields, which converge or diverge in negative or positive facular polarities. These findings support models which suggest the existence of small vertical flux tube bundles in faculae. A new method is proposed to get the relative formation heights of the multi-lines observed by MTR assuming the validity of a flux tube model for the faculae. We found that the Fe 1 6302.5 \AA line forms at a greater atmospheric height than the Fe 1 5250.2 \AA line.Comment: 20 pages, 9 figures, 3 tables, accepted for publication in Solar Physic

Do current and magnetic helicities have the same sign?

Current helicity, H c , and magnetic helicity, H m , are two main quantities used to characterize magnetic fields. For example, such quantities have been widely used to characterize solar active regions and their ejecta (magnetic clouds). It is commonly assumed that H c and H m have the same sign, but this has not been rigorously addressed beyond the simple case of linear force-free fields. We aim to answer whether H m H c ≥ 0 in general, and whether it is true over some useful set of magnetic fields. This question is addressed analytically and with numerical examples. The main focus is on cylindrically symmetric straight flux tubes, referred to as flux ropes (FRs), using the relative magnetic helicity with respect to a straight (untwisted) reference field. Counterexamples with H m H c < 0 have been found for cylindrically symmetric FRs with finite plasma pressure, and for force-free cylindrically symmetric FRs in which the poloidal field component changes direction. Our main result is a proof that H m H c ≥ 0 is true for force-free cylindrically symmetric FRs where the toroidal field and poloidal field components are each of a single sign, and the poloidal component does not exceed the toroidal component. We conclude that the conjecture that current and magnetic helicities have the same sign is not true in general, but it is true for a set of FRs of importance to coronal and heliospheric physics

Orai1 Channel Inhibition Preserves Left Ventricular Systolic Function and Normal Ca2+ Handling After Pressure Overload

Background: Orai1 is a critical ion channel subunit, best recognized as a mediator of storeoperated Ca2+ entry (SOCE) in non-excitable cells. SOCE has recently emerged as a key contributor of cardiac hypertrophy and heart failure but the relevance of Orai1 is still unclear. Methods: To test the role of these Orai1 channels in the cardiac pathophysiology, a transgenic mouse was generated with cardiomyocyte-specific expression of an ion pore-disruptive Orai1R91W mutant (C-dnO1). Synthetic chemistry and channel screening strategies were used to develop JPIII, a small-molecule Orai1 channel inhibitor suitable for in vivo delivery. Results: Adult mice subjected to transverse aortic constriction (TAC) developed cardiac hypertrophy and reduced ventricular function associated with increased Orai1 expression and Orai1-dependent SOCE (assessed by Mn2+ influx). C-dnO1 mice displayed normal cardiac electromechanical function and cellular excitation-contraction coupling despite reduced Orai1-dependent SOCE. 5 weeks after TAC, C-dnO1 mice were protected from systolic dysfunction (assessed by preserved left ventricular fractional shortening and ejection fraction) even if increased cardiac mass and pro-hypertrophic markers induction were observed. This is correlated with a protection from TAC-induced cellular Ca2+ signaling alterations (increased SOCE, decreased [Ca2+]i transients amplitude and decay rate, lower SR Ca2+ load and depressed cellular contractility) and SERCA2a downregulation in ventricular cardiomyocytes from C-dnO1 mice, associated with blunted Pyk2 signaling. There was also less fibrosis in heart sections from CdnO1 mice after TAC. Moreover, 3 weeks treatment with JPIII following 5 weeks of TAC confirmed the translational relevance of an Orai1 inhibition strategy during hypertrophic insult. Conclusions: The findings suggest a key role of cardiac Orai1 channels and the potential for Orai1 channel inhibitors as inotropic therapies for maintaining contractility reserve after hypertrophic stress

The Multiview Observatory for Solar Terrestrial Science (MOST)

We report on a study of the Multiview Observatory for Solar Terrestrial Science (MOST) mission that will provide comprehensive imagery and time series data needed to understand the magnetic connection between the solar interior and the solar atmosphere/inner heliosphere. MOST will build upon the successes of SOHO and STEREO missions with new views of the Sun and enhanced instrument capabilities. This article is based on a study conducted at NASA Goddard Space Flight Center that determined the required instrument refinement, spacecraft accommodation, launch configuration, and flight dynamics for mission success. MOST is envisioned as the next generation great observatory positioned to obtain three-dimensional information of large-scale heliospheric structures such as coronal mass ejections, stream interaction regions, and the solar wind itself. The MOST mission consists of 2 pairs of spacecraft located in the vicinity of Sun-Earth Lagrange points L4 (MOST1, MOST3) and L5 (MOST2 and MOST4). The spacecraft stationed at L4 (MOST1) and L5 (MOST2) will each carry seven remote-sensing and three in-situ instrument suites. MOST will also carry a novel radio package known as the Faraday Effect Tracker of Coronal and Heliospheric structures (FETCH). FETCH will have polarized radio transmitters and receivers on all four spacecraft to measure the magnetic content of solar wind structures propagating from the Sun to Earth using the Faraday rotation technique. The MOST mission will be able to sample the magnetized plasma throughout the Sun-Earth connected space during the mission lifetime over a solar cycle.Comment: 42 pages, 19 figures, 8 tables, to appear in J. Atmospheric and Solar Terrestrial Physic

Aging Skin: Nourishing from Out-In. Lessons from Wound Healing

Skin lesion therapy, peculiarly in the elderly, cannot be isolated from understanding that the skin is an important organ consisting of different tissues. Furthermore, dermis health is fundamental for epidermis integrity, and so adequate nourishment is mandatory in maintaining skin integrity. The dermis nourishes the epidermis, and a healthy epidermis protects the dermis from the environment, so nourishing the dermis through the epidermal barrier is a technical problem yet to be resolved. This is also a consequence of the laws and regulations restricting cosmetics, which cannot have properties that pass the epidermal layer. There is higher investment in cosmetics than in the pharmaceutical industry dealing with skin therapies, because the costs of drug registration are enormous and the field is unprofitable. Still, wound healing may be seen as an opportunity to “feed” the dermis directly. It could also verify whether providing substrates could promote efficient healing and test optimal skin integrity maintenance, if not skin rejuvenation, in an ever aging population