Predicted Colors and Flux Densities of Protostars in the Herschel PACS and SPIRE Filters

Upcoming surveys with the Herschel Space Observatory will yield far-IR photometry of large samples of young stellar objects, which will require careful interpretation. We investigate the color and luminosity diagnostics based on Herschel broad-band filters to identify and discern the properties of low-mass protostars. We compute a grid of 2,016 protostars in various physical congurations, present the expected flux densities and flux density ratios for this grid of protostars, and compare Herschel observations of three protostars to the model results. These provide useful constraints on the range of colors and fluxes of protostar in the Herschel filters. We find that Herschel data alone is likely a useful diagnostic of the envelope properties of young starsComment: Part of HOPS KP papers to the Herschel special A&A issu

Distinct phosphorylation clusters determines the signalling outcome of the free fatty acid receptor FFA4/GPR120

It is established that long-chain free fatty acids including ω-3 fatty acids mediate an array of biological responses through members of the free fatty acid receptor family, which includes FFA4. However, the signalling mechanisms and modes of regulation of this receptor class remain unclear. Here we employ mass spectrometry to determine that phosphorylation of mouse (m)FFAR4 occurs at five serine and threonine residues clustered in two separable regions of the C terminal tail, designated cluster 1 (Thr347, Thr349 and Ser350) and cluster 2 (Ser357 and Ser361). Mutation of these phospho-acceptor sites to alanine completely prevented phosphorylation of mFFA4 but did not limit receptor coupling to ERK1/2 activation. Rather an inhibitor of Gq/11 proteins completely prevented receptor signalling to ERK1/2. In contrast, the recruitment of arrestin 3, receptor internalization and activation of Akt were regulated by mFFA4 phosphorylation. The analysis of mFFA4 phosphorylation-dependent signalling was extended further by selective mutations of the phospho-acceptor sites. Mutations within cluster 2 did not affect agonist activation of Akt but instead significantly compromised receptor internalization and arrestin 3 recruitment. Distinctly, mutation of the phospho-acceptor sites within cluster 1 had no effect on receptor internalization and a less extensive effect on arrestin 3 recruitment, but significantly uncoupled the receptor from Akt activation. These unique observations define differential effects on signalling mediated by phosphorylation at distinct locations. This hallmark feature supports the possibility that the signalling outcome of mFFA4 activation can be determined by the pattern of phosphorylation (phosphorylation barcode) at the C-terminus of the receptor

On the nature of the deeply embedded protostar OMC-2 FIR 4

We use mid-infrared to submillimeter data from the Spitzer, Herschel, and APEX telescopes to study the bright sub-mm source OMC-2 FIR 4. We find a point source at 8, 24, and 70 $\mu$m, and a compact, but extended source at 160, 350, and 870 $\mu$m. The peak of the emission from 8 to 70 $\mu$m, attributed to the protostar associated with FIR 4, is displaced relative to the peak of the extended emission; the latter represents the large molecular core the protostar is embedded within. We determine that the protostar has a bolometric luminosity of 37 Lsun, although including more extended emission surrounding the point source raises this value to 86 Lsun. Radiative transfer models of the protostellar system fit the observed SED well and yield a total luminosity of most likely less than 100 Lsun. Our models suggest that the bolometric luminosity of the protostar could be just 12-14 Lsun, while the luminosity of the colder (~ 20 K) extended core could be around 100 Lsun, with a mass of about 27 Msun. Our derived luminosities for the protostar OMC-2 FIR 4 are in direct contradiction with previous claims of a total luminosity of 1000 Lsun (Crimier et al 2009). Furthermore, we find evidence from far-infrared molecular spectra (Kama et al. 2013, Manoj et al. 2013) and 3.6 cm emission (Reipurth et al 1999) that FIR 4 drives an outflow. The final stellar mass the protostar will ultimately achieve is uncertain due to its association with the large reservoir of mass found in the cold core.Comment: Accpeted by ApJ, 17 pages, 11 figure

Validation of the protein kinase PfCLK3 as a multistage cross-species malarial drug target.

The requirement for next generation anti-malarials to be both curative and transmission blocking necessitate the identification of new druggable molecular pathways. Here we identify a selective inhibitor to the Plasmodium falciparum protein kinase PfCLK3 which we use in combination with chemogenetics to validate PfCLK3 as a drug target acting at multiple parasite life stages. Consistent with a role for PfCLK3 in RNA splicing, inhibition results in the down-regulation of >400 essential parasite genes. Inhibiting plasmodium CLK3 mediates rapid killing of asexual blood stage P. falciparum and blockade of gametocyte development preventing transmission, as well as showing parasiticidal activity against P. berghei and P. knowlesi. Hence, our data establishes PfCLK3 as a target with the potential to deliver both symptomatic treatment and transmission blocking in malariapre-print7900 K

Sexual Dimorphism of Staminate- and Pistillate-Phase Flowers of Saponaria officinalis (Bouncing Bet) Affects Pollinator Behavior and Seed Set

The sequential separation of male and female function in flowers of dichogamous species allows for the evolution of differing morphologies that maximize fitness through seed siring and seed set. We examined staminate- and pistillate-phase flowers of protandrous Saponaria officinalis for dimorphism in floral traits and their effects on pollinator attraction and seed set. Pistillate-phase flowers have larger petals, greater mass, and are pinker in color, but due to a shape change, pistillate-phase flowers have smaller corolla diameters than staminate-phase flowers. There was no difference in nectar volume or sugar content one day after anthesis, and minimal evidence for UV nectar guide patterns in staminate- and pistillate-phase flowers. When presented with choice arrays, pollinators discriminated against pistillate-phase flowers based on their pink color. Finally, in an experimental garden, in 2012 there was a negative correlation between seed set of an open-pollinated, emasculated flower and pinkness (as measured by reflectance spectrometry) of a pistillate-phase flower on the same plant in plots covered with shade cloth. In 2013, clones of genotypes chosen from the 2012 plants that produced pinker flowers had lower seed set than those from genotypes with paler flowers. Lower seed set of pink genotypes was found in open-pollinated and hand-pollinated flowers, indicating the lower seed set might be due to other differences between pink and pale genotypes in addition to pollinator discrimination against pink flowers. In conclusion, staminate- and pistillate-phase flowers of S. officinalis are dimorphic in shape and color. Pollinators discriminate among flowers based on these differences, and individuals whose pistillate-phase flowers are most different in color from their staminate-phase flowers make fewer seeds. We suggest morphological studies of the two sex phases in dichogamous, hermaphroditic species can contribute to understanding the evolution of sexual dimorphism in plants without the confounding effects of genetic differences between separate male and female individuals

Radioactive Probes of the Supernova-Contaminated Solar Nebula: Evidence that the Sun was Born in a Cluster

We construct a simple model for radioisotopic enrichment of the protosolar nebula by injection from a nearby supernova, based on the inverse square law for ejecta dispersion. We find that the presolar radioisotopes abundances (i.e., in solar masses) demand a nearby supernova: its distance can be no larger than 66 times the size of the protosolar nebula, at a 90% confidence level, assuming 1 solar mass of protosolar material. The relevant size of the nebula depends on its state of evolution at the time of radioactivity injection. In one scenario, a collection of low-mass stars, including our sun, formed in a group or cluster with an intermediate- to high-mass star that ended its life as a supernova while our sun was still a protostar, a starless core, or perhaps a diffuse cloud. Using recent observations of protostars to estimate the size of the protosolar nebula constrains the distance of the supernova at 0.02 to 1.6 pc. The supernova distance limit is consistent with the scales of low-mass stars formation around one or more massive stars, but it is closer than expected were the sun formed in an isolated, solitary state. Consequently, if any presolar radioactivities originated via supernova injection, we must conclude that our sun was a member of such a group or cluster that has since dispersed, and thus that solar system formation should be understood in this context. In addition, we show that the timescale from explosion to the creation of small bodies was on the order of 1.8 Myr (formal 90% confidence range of 0 to 2.2 Myr), and thus the temporal choreography from supernova ejecta to meteorites is important. Finally, we can not distinguish between progenitor masses from 15 to 25 solar masses in the nucleosynthesis models; however, the 20 solar mass model is somewhat preferred.Comment: ApJ accepted, 19 pages, 3 figure

MISALIGNED DISKS IN THE BINARY PROTOSTAR IRS 43

Recent high angular resolution ($\sim$0.2") ALMA observations of the 1.1 mm continuum and of HCO+ J=3-2 and HCN J=3-2 gas towards the binary protostar IRS 43 reveal multiple Keplerian disks which are significantly misaligned ($\gt$ 60$^\circ$), both in inclination and position angle and also with respect to the binary orbital plane. Each stellar component has an associated circumstellar disk while the binary is surrounded by a circumbinary disk. Together with archival VLA measurements of the stellar positions over 25 years, and assuming a circular orbit, we use our continuum measurements to determine the binary separation, a = 74 $\pm$ 4 AU, and its inclination, i $\lt$ 30$^\circ$. The misalignment in this system suggests that turbulence has likely played a major role in the formation of IRS 43.Comment: 7 pages, 4 figure

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses