Planar cell polarity genes Frizzled3a, Vangl2, and Scribble are required for spinal commissural axon guidance

Background A fundamental feature of early nervous system development is the guidance of axonal projections to their targets in order to assemble neural circuits that control behavior. Spinal commissural neurons are an attractive model to investigate the multiple guidance cues that control growth cone navigation both pre- and post-midline crossing, as well as along both the dorsal–ventral (D–V) and anterior–posterior (A–P) axes. Accumulating evidence suggests that guidance of spinal commissural axons along the A–P axis is dependent on components of the planar cell polarity (PCP) signaling pathway. In the zebrafish, the earliest born spinal commissural neuron to navigate the midline and turn rostrally is termed commissural primary ascending (CoPA). Unlike mammalian systems, CoPA axons cross the midline as a single axon and allow an analysis of the role of PCP components in anterior pathfinding in single pioneering axons. Results Here, we establish CoPA cells in the zebrafish spinal cord as a model system for investigating the molecular function of planar cell polarity signaling in axon guidance. Using mutant analysis, we show that the functions of Fzd3a and Vangl2 in the anterior turning of commissural axons are evolutionarily conserved in teleosts. We extend our findings to reveal a role for the PCP gene scribble in the anterior guidance of CoPA axons. Analysis of single CoPA axons reveals that these commissural axons become responsive to PCP-dependent anterior guidance cues even prior to midline crossing. When midline crossing is prevented by dcc gene knockdown, ipsilateral CoPA axons still extend axons anteriorly in response to A–P guidance cues. We show that this ipsilateral anterior pathfinding that occurs in the absence of midline crossing is dependent on PCP signaling. Conclusion Our results demonstrate that anterior guidance decisions by CoPA axons are dependent on the function of planar cell polarity genes both prior to and after midline crossing

Vitamin D in obesity

Purpose of review: Vitamin D is essential for bone health, and may also have important functions in immunity and other systems. Vitamin D deficiency is common, and testing and supplementation is increasing. Serum vitamin D is lower in obese people; it is important to understand the mechanism of this effect and whether it indicates clinically significant deficiency. Recent findings: Vitamin D is fat soluble, and distributed into fat, muscle, liver, and serum. All of these compartments are increased in volume in obesity, so the lower vitamin D likely reflects a volumetric dilution effect and whole body stores of vitamin D may be adequate. Despite lower serum vitamin D, obese adults do not have higher bone turnover or lower bone mineral density. Patients undergoing bariatric surgery do have bone loss, and ensuring vitamin D sufficiency in these patients may help to attenuate bone loss. Summary: Lower vitamin D in obese people is a consistent finding across age, ethnicity, and geography. This may not always reflect a clinical problem. Obese people need higher loading doses of vitamin D to achieve the same serum 25-hydroxyvitamin D as normal weight

Direct Observation of Dynamic Symmetry Breaking above Room Temperature in Methylammonium Lead Iodide Perovskite

Lead halide perovskites such as methylammonium lead triiodide (MAPI) have outstanding optical and electronic properties for photovoltaic applications, yet a full understanding of how this solution processable material works so well is currently missing. Previous research has revealed that MAPI possesses multiple forms of static disorder regardless of preparation method, which is surprising in light of its excellent performance. Using high energy resolution inelastic X-ray (HERIX) scattering, we measure phonon dispersions in MAPI and find direct evidence for another form of disorder in single crystals: large amplitude anharmonic zone-edge rotational instabilities of the PbI_6 octahedra that persist to room temperature and above, left over from structural phase transitions that take place tens to hundreds of degrees below. Phonon calculations show that the orientations of the methylammonium couple strongly and cooperatively to these modes. The result is a non-centrosymmetric, instantaneous local structure, which we observe in atomic pair distribution function (PDF) measurements. This local symmetry breaking is unobservable by Bragg diffraction, but can explain key material properties such as the structural phase sequence, ultra low thermal transport, and large minority charge carrier lifetimes despite moderate carrier mobility.Comment: 30 pages, 11 figure

Undergraduate medical textbooks do not provide adequate information on intravenous fluid therapy: a systematic survey and suggestions for improvement

<b>Background</b><p></p> Inappropriate prescribing of intravenous (IV) fluid, particularly 0.9% sodium chloride, causes post-operative complications. Fluid prescription is often left to junior medical staff and is frequently poorly managed. One reason for poor intravenous fluid prescribing practices could be inadequate coverage of this topic in the textbooks that are used.<p></p> <b>Methods</b><p></p> We formulated a comprehensive set of topics, related to important common clinical situations involving IV fluid therapy, (routine fluid replacement, fluid loss, fluids overload) to assess the adequacy of textbooks in common use. We assessed 29 medical textbooks widely available to students in the UK, scoring the presence of information provided by each book on each of the topics. The scores indicated how fully the topics were considered: not at all, partly, and adequately. No attempt was made to judge the quality of the information, because there is no consensus on these topics.<p></p> <b>Results</b><p></p> The maximum score that a book could achieve was 52. Three of the topics we chose were not considered by any of the books. Discounting these topics as “too esoteric”, the maximum possible score became 46. One textbook gained a score of 45, but the general score was poor (median 11, quartiles 4, 21). In particular, coverage of routine postoperative management was inadequate.<p></p> <b>Conclusions</b><p></p> Textbooks for undergraduates cover the topic of intravenous therapy badly, which may partly explain the poor knowledge and performance of junior doctors in this important field. Systematic revision of current textbooks might improve knowledge and practice by junior doctors. Careful definition of the remit and content of textbooks should be applied more widely to ensure quality and “fitness for purpose”, and avoid omission of vital knowledge

Where are the Fossils of the First Galaxies? I. Local Volume Maps and Properties of the Undetected Dwarfs

We present a new method for generating initial conditions for LCDM N-body simulations which provides the dynamical range necessary to follow the evolution and distribution of the fossils of the first galaxies on Local Volume, 5-10 Mpc, scales. The initial distribution of particles represents the position, velocity and mass distribution of the dark and luminous halos extracted from pre-reionization simulations. We confirm previous results that ultra-faint dwarfs have properties compatible with being well preserved fossils of the first galaxies. However, because the brightest pre-reionization dwarfs form preferentially in biased regions, they most likely merge into non-fossil halos with circular velocities >20-30 km/s. Hence, we find that the maximum luminosity of true-fossils in the Milky Way is L_V<10^5 L_solar, casting doubts on the interpretation that some classical dSphs are true-fossils. In addition, we argue that most ultra-faints at small galactocentric distance, R<50 kpc, had their stellar properties modified by tides, while a large population of fossils is still undetected due to their extremely low surface brightness log(Sigma_V) < -1.4. We estimate that the region outside R_50 (~ 400 kpc) up to 1 Mpc from the Milky Way contains about a hundred true fossils of the first galaxies with V-band luminosities 10^3 - 10^5 L_solar and half-light radii, r_hl ~ 100-1000 pc.Comment: published in ApJ October 2011 with minor revisions V. 741 article ID. 1

Free 25-hydroxyvitamin D is low in obesity, but there are no adverse associations with bone health

Background: The mechanism and clinical significance of low circulating 25-hydroxyvitamin D [25(OH)D] in obese people are unknown. Low total 25(OH)D may be due to low vitamin D–binding proteins (DBPs) or faster metabolic clearance. However, obese people have a higher bone mineral density (BMD), which suggests that low 25(OH)D may not be associated with adverse consequences for bone. Objective: We sought to determine whether 1) vitamin D metabolism and 2) its association with bone health differ by body weight. Design: We conducted a cross-sectional observational study of 223 normal-weight, overweight, and obese men and women aged 25–75 y in South Yorkshire, United Kingdom, in the fall and spring. A subgroup of 106 subjects was also assessed in the winter. We used novel techniques, including an immunoassay for free 25(OH)D, a stable isotope for the 25(OH)D3 half-life, and high-resolution quantitative tomography, to make a detailed assessment of vitamin D physiology and bone health. Results: Serum total 25(OH)D was lower in obese and overweight subjects than in normal-weight subjects in the fall and spring (geometric means: 45.0 and 40.8 compared with 58.6 nmol/L, respectively; P < 0.001) but not in the winter. Serum 25(OH)D was inversely correlated with body mass index (BMI) in the fall and spring and in the winter. Free 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] were lower in obese subjects. DBP, the DBP genotype, and the 25(OH)D3 half-life did not differ between BMI groups. Bone turnover was lower, and bone density was higher, in obese people. Conclusions: Total and free 25(OH)D and 1,25(OH)2D are lower at higher BMI, which cannot be explained by lower DBP or the shorter half-life of 25(OH)D3. We speculate that low 25(OH)D in obesity is due to a greater pool of distribution. Lower 25(OH)D may not reflect at-risk skeletal health in obese people, and BMI should be considered when interpreting serum 25(OH)D as a marker of vitamin D status

Where are the Fossils of the First Galaxies? II. True Fossils, Ghost Halos, and the Missing Bright Satellites

We use a new set of cold dark matter simulations of the local universe to investigate the distribution of fossils of primordial dwarf galaxies within, and around the Milky Way. Throughout, we build upon previous results showing agreement between the observed stellar properties of a subset of the ultra-faint dwarfs and our simulated fossils. Here, we show that fossils of the first galaxies have galactocentric distributions and cumulative luminosity functions consistent with observations. In our model there are ~ 300 luminous satellites orbiting the Milky Way, ~50-70% of which are well preserved fossils, with this fraction decreasing with galactocentric distance. Within the Milky Way virial radius, the majority of these fossils have luminosities L_V<10^5 L_solar. This work produces an overabundance of bright dwarf satellites (L_V > 10^4 L_solar) with respect to observations where observations are nearly complete. The "bright satellite problem" is most evident in the outer parts of the Milky Way. We estimate that, although relatively bright, the primordial stellar populations are very diffuse, producing a population with surface brightnesses below surveys` detection limits and are easily stripped by tidal forces. Although we cannot yet present unmistakable evidence for the existence of the fossils of first galaxies in the Local Group, the results of our studies suggest observational strategies that may demonstrate their existence. Primarily, the detection of "ghost halos" of primordial stars around isolated dwarfs would prove that stars formed in minihalos (M<10^8 M_solar) before reionization, and strongly suggest that at least a fraction of the ultra-faint dwarfs are fossils of the first galaxies.Comment: publishing in ApJ with minor revisions in October 2011 V. 741 article ID. 1

Hot high-mass accretion disk candidates

To better understand the physical properties of accretion disks in high-mass star formation, we present a study of a 12 high-mass accretion disk candidates observed at high spatial resolution with the Australia Telescope Compact Array (ATCA) in the NH3 (4,4) and (5,5) lines. Almost all sources were detected in NH3, directly associated with CH3OH Class II maser emission. From the remaining eleven sources, six show clear signatures of rotation and/or infall motions. These signatures vary from velocity gradients perpendicular to the outflows, to infall signatures in absorption against ultracompact HII regions, to more spherical infall signatures in emission. Although our spatial resolution is ~1000AU, we do not find clear Keplerian signatures in any of the sources. Furthermore, we also do not find flattened structures. In contrast to this, in several of the sources with rotational signatures, the spatial structure is approximately spherical with sizes exceeding 10^4 AU, showing considerable clumpy sub-structure at even smaller scales. This implies that on average typical Keplerian accretion disks -- if they exist as expected -- should be confined to regions usually smaller than 1000AU. It is likely that these disks are fed by the larger-scale rotating envelope structure we observe here. Furthermore, we do detect 1.25cm continuum emission in most fields of view.Comment: 21 pages, 32 figures, accepted for ApJS. A high-resolution version can be found at http://www.mpia.de/homes/beuther/papers.htm