Discovery and Functional Annotation of SIX6 Variants in Primary Open-Angle Glaucoma

Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR) = 1.32, p = 3.87×10−11). SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345), which was associated significantly with POAG (OR = 1.27, p = 4.2×10−10) in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish) complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141) have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141). Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss

High resolution mapping of a novel late blight resistance gene Rpi-avll, from the wild Bolivian species Solanum avilesii

Both Mexico and South America are rich in Solanum species that might be valuable sources of resistance (R) genes to late blight (Phytophthora infestans). Here, we focus on an R gene present in the diploid Bolivian species S. avilesii. The genotype carrying the R gene was resistant to eight out of 10 Phytophthora isolates of various provenances. The identification of a resistant phenotype and the generation of a segregating population allowed the mapping of a single dominant R gene, Rpi-avl1, which is located in an R gene cluster on chromosome 11. This R gene cluster is considered as an R gene “hot spot”, containing R genes to at least five different pathogens. High resolution mapping of the Rpi-avl1 gene revealed a marker co-segregating in 3890 F1 individuals, which may be used for marker assisted selection in breeding programs and for further cloning of Rpi-avl

Near-Infrared Imaging Polarimetry of Inner Region of GG Tau A Disk

By performing non-masked polarization imaging with Subaru/HiCIAO, polarized scattered light from the inner region of the disk around the GG Tau A system was successfully detected in the $H$ band with a spatial resolution of approximately 0.07\arcsec, revealing the complicated inner disk structures around this young binary. This paper reports the observation of an arc-like structure to the north of GG Tau Ab and part of a circumstellar structure that is noticeable around GG Tau Aa extending to a distance of approximately 28 AU from the primary star. The speckle noise around GG Tau Ab constrains its disk radius to <13 AU. Based on the size of the circumbinary ring and the circumstellar disk around GG Tau Aa, the semi-major axis of the binary's orbit is likely to be 62 AU. A comparison of the present observations with previous ALMA and near-infrared (NIR) H$_2$ emission observations suggests that the north arc could be part of a large streamer flowing from the circumbinary ring to sustain the circumstellar disks. According to the previous studies, the circumstellar disk around GG Tau Aa has enough mass and can sustain itself for a duration sufficient for planet formation; thus, our study indicates that planets can form within close (separation $\lesssim$ 100 AU) young binary systems.Comment: Accepted for publication in AJ, 12 pages, 5 figure

A Substellar Companion to Pleiades HII 3441

We find a new substellar companion to the Pleiades member star, Pleiades HII 3441, using the Subaru telescope with adaptive optics. The discovery is made as part of the high-contrast imaging survey to search for planetary-mass and substellar companions in the Pleiades and young moving groups. The companion has a projected separation of 0".49 +/- 0".02 (66 +/- 2 AU) and a mass of 68 +/- 5 M_J based on three observations in the J-, H-, and K_S-band. The spectral type is estimated to be M7 (~2700 K), and thus no methane absorption is detected in the H band. Our Pleiades observations result in the detection of two substellar companions including one previously reported among 20 observed Pleiades stars, and indicate that the fraction of substellar companions in the Pleiades is about 10.0 +26.1/-8.8 %. This is consistent with multiplicity studies of both the Pleiades stars and other open clusters.Comment: Main text (14 pages, 4 figures, 4 tables), and Supplementary data (8 pages, 3 tables). Accepted for Publications of Astronomical Society of Japa

Planar Cell Polarity Acts Through Septins to Control Collective Cell Movement and Ciliogenesis

The planar cell polarity (PCP) signaling pathway governs collective cell movements during vertebrate embryogenesis, and certain PCP proteins are also implicated in the assembly of cilia. The septins are cytoskeletal proteins controlling behaviors such as cell division and migration. Here, we identified control of septin localization by the PCP protein Fritz as a crucial control point for both collective cell movement and ciliogenesis in Xenopus embryos. We also linked mutations in human Fritz to Bardet-Biedl and Meckel-Gruber syndromes, a notable link given that other genes mutated in these syndromes also influence collective cell movement and ciliogenesis. These findings shed light on the mechanisms by which fundamental cellular machinery, such as the cytoskeleton, is regulated during embryonic development and human disease

Advancing specificity in delirium: The delirium subtyping initiative

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning

Application of machine learning algorithms to the study of noise artifacts in gravitational-wave data

The sensitivity of searches for astrophysical transients in data from the Laser Interferometer Gravitational-wave Observatory (LIGO) is generally limited by the presence of transient, non-Gaussian noise artifacts, which occur at a high enough rate such that accidental coincidence across multiple detectors is non-negligible. These “glitches” can easily be mistaken for transient gravitational-wave signals, and their robust identification and removal will help any search for astrophysical gravitational waves. We apply machine-learning algorithms (MLAs) to the problem, using data from auxiliary channels within the LIGO detectors that monitor degrees of freedom unaffected by astrophysical signals. Noise sources may produce artifacts in these auxiliary channels as well as the gravitational-wave channel. The number of auxiliary-channel parameters describing these disturbances may also be extremely large; high dimensionality is an area where MLAs are particularly well suited. We demonstrate the feasibility and applicability of three different MLAs: artificial neural networks, support vector machines, and random forests. These classifiers identify and remove a substantial fraction of the glitches present in two different data sets: four weeks of LIGO’s fourth science run and one week of LIGO’s sixth science run. We observe that all three algorithms agree on which events are glitches to within 10% for the sixth-science-run data, and support this by showing that the different optimization criteria used by each classifier generate the same decision surface, based on a likelihood-ratio statistic. Furthermore, we find that all classifiers obtain similar performance to the benchmark algorithm, the ordered veto list, which is optimized to detect pairwise correlations between transients in LIGO auxiliary channels and glitches in the gravitational-wave data. This suggests that most of the useful information currently extracted from the auxiliary channels is already described by this model. Future performance gains are thus likely to involve additional sources of information, rather than improvements in the classification algorithms themselves. We discuss several plausible sources of such new information as well as the ways of propagating it through the classifiers into gravitational-wave searches

High-contrast Polarimetry Observation of T Tau Circumstellar Environment

We conducted high-contrast polarimetry observations of T Tau in the H-band, using the HiCIAO instrument mounted on the Subaru Telescope, revealing structures as near as 0.\arcsec1 from the stars T Tau N and T Tau S. The whole T Tau system is found to be surrounded by nebula-like envelopes, and several outflow-related structures are detected in these envelopes. We analyzed the detailed polarization patterns of the circumstellar structures near each component of this triple young star system and determined constraints on the circumstellar disks and outflow structures. We suggest that the nearly face-on circumstellar disk of T Tau N is no larger than 0.\arcsec8, or 117 AU, in the northwest, based on the existence of a hole in this direction, and no larger than 0.\arcsec27, or 40 AU, in the south. A new structure "N5" extends to about 0.\arcsec42, or 59 AU, on the southwest of the star, believed to be part of the disk. We suggest that T Tau S is surrounded by a highly inclined circumbinary disk with a radius of about 0.\arcsec3, or 44 AU, with a position angle of about 30$^\circ$, that is misaligned with the orbit of the T Tau S binary. After analyzing the positions and polarization vector patterns of the outflow-related structures, we suggest that T Tau S should trigger the well-known E-W outflow, and is also likely to be responsible for a southwest precessing outflow "coil" and a possible south outflow.Comment: 12 pages, 6 figures, accepted by The Astrophysical Journa