Volatile-Rich Circumstellar Gas in the Unusual 49 Ceti Debris Disk

We present Hubble Space Telescope STIS far-UV spectra of the edge-on disk around 49 Ceti, one of the very few debris disks showing sub-mm CO emission. Many atomic absorption lines are present in the spectra, most of which arise from circumstellar gas lying along the line-of-sight to the central star. We determined the line-of-sight CI column density, estimated the total carbon column density, and set limits on the OI column density. Surprisingly, no line-of-sight CO absorption was seen. We discuss possible explanations for this non-detection, and present preliminary estimates of the carbon abundances in the line-of-sight gas. The C/Fe ratio is much greater than the solar value, suggesting that 49 Cet harbors a volatile-rich gas disk similar to that of Beta Pictoris.Comment: Accepted for publication in ApJ Letters. 5 pages, 4 figure

Long Term Neuroprotective Effects of Human Adipose-Derived Stem Cells in Neonatal Rats Post Hypoxic Ischemic Encephalopathy

Background: Hypoxemic ischemic encephalopathy (HIE) is a major cause of morbidity and mortality in the neonatal population. Recent research has shown human adipose stem cells (hASCs) to have neuroprotective effects in animal models of HIE. This study tested the hypothesis that neurodevelopmental outcomes would be improved using hASC therapy in term neonatal HIE rat model. Methods: Seven day old rats underwent left carotid artery ligation followed by 8% oxygen for 120 minutes, or carotid isolation in shams. Forty-eight hours after surgery half of the rats received hASCs and half normal saline (NS) intravenously. Rota-rod and cylinder tests were used to assess skill learning, balance, coordination, and symmetry of limb use at 2, 4 and 6 weeks of life. Results: HIE rats treated with hASCs traveled further on Rota-rod (p=0.03) when compared to HIE with NS groups. Those in the HIE-hASC group had significant improvement in the usage of the affected limb at week 6 (p=0.03) compared to those with HIE and NS. Rats receiving hASCs post HIE had less cortical atrophy compared to those with HIE and NS. Conclusions: Rats with HIE treated with hASCs showed improvement in long-term neurodevelopmental aspects and decreased cortical atrophy compared to HIE control group

Decreased Anti-Inflammatory Responses to Vitamin D in Neonatal Neutrophils

Neutrophil activity is prolonged in newborns, suggesting decreased exposure and/or responses to immunosuppressive modulators, such as 1,25-hydroxyvitamin D3 (1,25-vit D3). We hypothesized that 1,25-vit D3 suppresses neutrophil activation and that this response is impaired in newborns. Consistent with this, 1,25-vit D3 decreased LPS-induced expression of macrophage inflammatory protein-1β and VEGF in adult, but not neonatal, neutrophils. Expression of vitamin D receptor (VDR) and 25-hydroxyvitamin D3-1α-hydroxylase was reduced in neonatal, relative to adult neutrophils. Moreover, 1,25-vit D3 induced VDR gene expression in activated adult, but not neonatal, neutrophils. 1,25-vit D3 also suppressed expression of cyclooxygenase-2 and induced expression of 5-lipoxygenase in LPS-exposed adult neutrophils, while neonatal cells were not affected. 1,25-vit D3 had no effect on respiratory burst in either adult or neonatal cells. Anti-inflammatory activity of vitamin D is impaired in neonatal neutrophils, and this may be due to decreased expression of VDR and 1α-hydroxylase. Insensitivity to 1,25-vit D3 may contribute to chronic inflammation in neonates

Mechanisms Mediating the Biologic Activity of Synthetic Proline, Glycine, and Hydroxyproline Polypeptides in Human Neutrophils

The accumulation of neutrophils at sites of tissue injury or infection is mediated by chemotactic factors released as part of the inflammatory process. Some of these factors are generated as a direct consequence of tissue injury or infection, including degradation fragments of connective tissue collagen and bacterial- or viral-derived peptides containing collagen-related structural motifs. In these studies, we examined biochemical mechanisms mediating the biologic activity of synthetic polypeptides consisting of repeated units of proline (Pro), glycine (Gly), and hydroxyproline (Hyp), major amino acids found within mammalian and bacterial collagens. We found that the peptides were chemoattractants for neutrophils. Moreover, their chemotactic potency was directly related to their size and composition. Thus, the pentameric peptides (Pro-Pro-Gly)(5) and (Pro-Hyp-Gly)(5) were more active in inducing chemotaxis than the corresponding decameric peptides (Pro-Pro-Gly)(10) and (Pro-Hyp-Gly)(10). In addition, the presence of Hyp in peptides reduced chemotactic activity. The synthetic peptides were also found to reduce neutrophil apoptosis. In contrast to chemotaxis, this activity was independent of peptide size or composition. The effects of the peptides on both chemotaxis and apoptosis were blocked by inhibitors of phosphatidylinositol 3-kinase (PI3-K) and p38 mitogen-activated protein (MAP) kinase. However, only (Pro-Pro-Gly)(5) and (Pro-Pro-Gly)(10) induced expression of PI3-K and phosphorylation of p38 MAP kinase, suggesting a potential mechanism underlying reduced chemotactic activity of Hyp-containing peptides. Although none of the synthetic peptides tested had any effect on intracellular calcium mobilization, each induced nuclear binding activity of the transcription factor NF-κB. These findings indicate that polymeric polypeptides containing Gly-X-Y collagen-related structural motifs promote inflammation by inducing chemotaxis and blocking apoptosis. However, distinct calcium-independent signaling pathways appear to be involved in these activities

The surprisingly low carbon mass in the debris disk around HD 32297

Gas has been detected in a number of debris disks. It is likely secondary, i.e. produced by colliding solids. Here, we report ALMA Band 8 observations of neutral carbon in the CO-rich debris disk around the 15--30 Myr old A-type star HD 32297. We find that C$^0$ is located in a ring at $\sim$110 au with a FWHM of $\sim$80 au, and has a mass of $(3.5\pm0.2)\times10^{-3}$ M$_\oplus$. Naively, such a surprisingly small mass can be accumulated from CO photo-dissociation in a time as short as $\sim$10$^4$ yr. We develop a simple model for gas production and destruction in this system, properly accounting for CO self-shielding and shielding by neutral carbon, and introducing a removal mechanism for carbon gas. We find that the most likely scenario to explain both C$^0$ and CO observations, is one where the carbon gas is rapidly removed on a timescale of order a thousand years and the system maintains a very high CO production rate of $\sim$15 M$_\oplus$ Myr$^{-1}$, much higher than the rate of dust grind-down. We propose a possible scenario to meet these peculiar conditions: the capture of carbon onto dust grains, followed by rapid CO re-formation and re-release. In steady state, CO would continuously be recycled, producing a CO-rich gas ring that shows no appreciable spreading over time. This picture might be extended to explain other gas-rich debris disks.Comment: accepted for publication in the Ap

Theta Rhythms Coordinate Hippocampal–Prefrontal Interactions in a Spatial Memory Task

Decision-making requires the coordinated activity of diverse brain structures. For example, in maze-based tasks, the prefrontal cortex must integrate spatial information encoded in the hippocampus with mnemonic information concerning route and task rules in order to direct behavior appropriately. Using simultaneous tetrode recordings from CA1 of the rat hippocampus and medial prefrontal cortex, we show that correlated firing in the two structures is selectively enhanced during behavior that recruits spatial working memory, allowing the integration of hippocampal spatial information into a broader, decision-making network. The increased correlations are paralleled by enhanced coupling of the two structures in the 4- to 12-Hz theta-frequency range. Thus the coordination of theta rhythms may constitute a general mechanism through which the relative timing of disparate neural activities can be controlled, allowing specialized brain structures to both encode information independently and to interact selectively according to current behavioral demands

The Genomic and Evolutionary Landscapes of Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations