The test case of HD26965: difficulties disentangling weak Doppler signals from stellar activity

We report the discovery of a radial velocity signal that can be interpreted as a planetary-mass candidate orbiting the K dwarf HD26965, with an orbital period of 42.364$\pm$0.015 days, or alternatively, as the presence of residual, uncorrected rotational activity in the data. Observations include data from HIRES, PFS, CHIRON, and HARPS, where 1,111 measurements were made over 16 years. Our best solution for HD26965 $b$ is consistent with a super-Earth that has a minimum mass of 6.92$\pm$0.79 M$_{\oplus}$ orbiting at a distance of 0.215$\pm$0.008 AU from its host star. We have analyzed the correlation between spectral activity indicators and the radial velocities from each instrument, showing moderate correlations that we include in our model. From this analysis, we recover a $\sim$38 day signal, which matches some literature values of the stellar rotation period. However, from independent Mt. Wilson HK data for this star, we find evidence for a significant 42 day signal after subtraction of longer period magnetic cycles, casting doubt on the planetary hypothesis for this period. Although our statistical model strongly suggests that the 42-day signal is Doppler in origin, we conclude that the residual effects of stellar rotation are difficult to fully model and remove from this dataset, highlighting the difficulties to disentangle small planetary signals and photospheric noise, particularly when the orbital periods are close to the rotation period of the star. This study serves as an excellent test case for future works that aim to detect small planets orbiting `Sun-like' stars using radial velocity measurements.Comment: 16 pages, 10 figures, 13 tables, accepted for publication in A

Retinal regeneration in adult zebrafish requires regulation of TGFβ signaling

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99623/1/glia22549.pd

Mitochondria directly donate their membrane to form autophagosomes during a novel mechanism of parkin-associated mitophagy

BACKGROUND: Autophagy (macroautophagy), a cellular process of “self-eating”, segregates damaged/aged organelles into vesicles, fuses with lysosomes, and enables recycling of the digested materials. The precise origin(s) of the autophagosome membrane is unclear and remains a critical but unanswered question. Endoplasmic reticulum, mitochondria, Golgi complex, and the plasma membrane have been proposed as the source of autophagosomal membranes. FINDINGS: Using electron microscopy, immunogold labeling techniques, confocal microscopy, and flow cytometry we show that mitochondria can directly donate their membrane material to form autophagosomes. We expand upon earlier studies to show that mitochondria donate their membranes to form autophagosomes during basal and drug-induced autophagy. Moreover, electron microscopy and immunogold labeling studies show the first physical evidence of mitochondria forming continuous structures with LC3-labeled autophagosomes. The mitochondria forming these structures also stain positive for parkin, indicating that these mitochondrial-formed autophagosomes represent a novel mechanism of parkin-associated mitophagy. CONCLUSIONS: With the on-going debate regarding autophagosomal membrane origin, this report demonstrates that mitochondria can donate membrane materials to form autophagosomes. These structures may also represent a novel form of mitophagy where the mitochondria contribute to the formation of autophagosomes. This novel form of parkin-associated mitophagy may be a more efficient bio-energetic process compared with de novo biosynthesis of a new membrane, particularly if the membrane is obtained, at least partly, from the organelle being targeted for later degradation in the mature autolysosome

An outflow in the Seyfert ESO 362-G18 revealed by Gemini-GMOS/IFU Observations

We present two-dimensional stellar and gaseous kinematics of the inner 0.7 $\times$ 1.2 kpc$^{2}$ of the Seyfert galaxy ESO 362-G18, derived from optical spectra obtained with the GMOS/IFU on the Gemini South telescope at a spatial resolution of $\approx$170 pc and spectral resolution of 36 km s$^{-1}$. ESO 362-G18 is a strongly perturbed galaxy of morphological type Sa or S0/a, with a minor merger approaching along the NE direction. Previous studies have shown that the [OIII] emission shows a fan-shaped extension of $\approx$ 10\arcsec\ to the SE. We detect the [OIII] doublet, [NII] and H${\alpha}$ emission lines throughout our field of view. The stellar kinematics is dominated by circular motions in the galaxy plane, with a kinematic position angle of $\approx$137$^{\circ}$. The gas kinematics is also dominated by rotation, with kinematic position angles ranging from 122$^{\circ}$ to 139$^{\circ}$. A double-Gaussian fit to the [OIII]$\lambda$5007 and H${\alpha}$ lines, which have the highest signal to noise ratios of the emission lines, reveal two kinematic components: (1) a component at lower radial velocities which we interpret as gas rotating in the galactic disk; and (2) a component with line of sight velocities 100-250 km s$^{-1}$ higher than the systemic velocity, interpreted as originating in the outflowing gas within the AGN ionization cone. We estimate a mass outflow rate of 7.4 $\times$ 10$^{-2}$ M$_{\odot}$ yr$^{-1}$ in the SE ionization cone (this rate doubles if we assume a biconical configuration), and a mass accretion rate on the supermassive black hole (SMBH) of 2.2 $\times$ 10$^{-2}$ M$_{\odot}$ yr$^{-1}$. The total ionized gas mass within $\sim$84 pc of the nucleus is 3.3 $\times$ 10$^{5}$ M$_{\odot}$; infall velocities of $\sim$34 km s$^{-1}$ in this gas would be required to feed both the outflow and SMBH accretion.Comment: 18 pages, 14 figure

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

Dopamine-Induced Conformational Changes in Alpha-Synuclein

Background: Oligomerization and aggregation of α-synuclein molecules play a major role in neuronal dysfunction and loss in Parkinson's disease [1]. However, α-synuclein oligomerization and aggregation have mostly been detected indirectly in cells using detergent extraction methods [2], [3], [4]. A number of in vitro studies showed that dopamine can modulate the aggregation of α-synuclein by inhibiting the formation of or by disaggregating amyloid fibrils [5], [6], [7]. Methodology/Principal Findings: Here, we show that α-synuclein adopts a variety of conformations in primary neuronal cultures using fluorescence lifetime imaging microscopy (FLIM). Importantly, we found that dopamine, but not dopamine agonists, induced conformational changes in α-synuclein which could be prevented by blocking dopamine transport into the cell. Dopamine also induced conformational changes in α-synuclein expressed in neuronal cell lines, and these changes were also associated with alterations in oligomeric/aggregated species. Conclusion/Significance: Our results show, for the first time, a direct effect of dopamine on the conformation of α-synuclein in neurons, which may help explain the increased vulnerability of dopaminergic neurons in Parkinson's disease

An Eccentric Massive Jupiter Orbiting a Subgiant on a 9.5-day Period Discovered in the <i>Transiting Exoplanet Survey Satellite</i> Full Frame Images

We report the discovery of TOI-172 b from the Transiting Exoplanet Survey Satellite (TESS) mission, a massive hot Jupiter transiting a slightly evolved G star with a 9.48-day orbital period. This is the first planet to be confirmed from analysis of only the TESS full frame images, because the host star was not chosen as a two-minute cadence target. From a global analysis of the TESS photometry and follow-up observations carried out by the TESS Follow-up Observing Program Working Group, TOI-172 (TIC 29857954) is a slightly evolved star with an effective temperature of T eff = 5645 ± 50 K, a mass of M ⋆ = {1.128}-0.061+0.065 M ⊙, radius of R ⋆ = {1.777}-0.044+0.047 R ⊙, a surface gravity of log g ⋆ = {3.993}-0.028+0.027, and an age of {7.4}-1.5+1.6 {Gyr}. Its planetary companion (TOI-172 b) has a radius of R P = {0.965}-0.029+0.032 R J, a mass of M P = {5.42}-0.20+0.22 M J, and is on an eccentric orbit (e={0.3806}-0.0090+0.0093). TOI-172 b is one of the few known massive giant planets on a highly eccentric short-period orbit. Future study of the atmosphere of this planet and its system architecture offer opportunities to understand the formation and evolution of similar systems

The Global Alliance for Infections in Surgery : defining a model for antimicrobial stewardship-results from an international cross-sectional survey

Background: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. Methods: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. Results: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p <0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%). Conclusion: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.Peer reviewe

Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors

The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site (CD4bs) antibodies and analyzed 16 co-crystal structures –8 determined here– of CD4bs antibodies from 14 donors. The 16 antibodies segregated by recognition mode and developmental ontogeny into two types: CDR H3-dominated and VH-gene-restricted. Both could achieve greater than 80% neutralization breadth, and both could develop in the same donor. Although paratope chemistries differed, all 16 gp120-CD4bs antibody complexes showed geometric similarity, with antibody-neutralization breadth correlating with antibody-angle of approach relative to the most effective antibody of each type. The repertoire for effective recognition of the CD4 supersite thus comprises antibodies with distinct paratopes arrayed about two optimal geometric orientations, one achieved by CDR H3 ontogenies and the other achieved by VH-gene-restricted ontogenies