The Great Observatories All-Sky LIRG Survey: Comparison of Ultraviolet and Far-Infrared Properties

The Great Observatories All-sky LIRG Survey (GOALS) consists of a complete sample of 202 Luminous Infrared Galaxies (LIRGs) selected from the IRAS Revised Bright Galaxy Sample (RBGS). The galaxies span the full range of interaction stages, from isolated galaxies to interacting pairs to late stage mergers. We present a comparison of the UV and infrared properties of 135 galaxies in GOALS observed by GALEX and Spitzer. For interacting galaxies with separations greater than the resolution of GALEX and Spitzer (2-6"), we assess the UV and IR properties of each galaxy individually. The contribution of the FUV to the measured SFR ranges from 0.2% to 17.9%, with a median of 2.8% and a mean of 4.0 +/- 0.4%. The specific star formation rate of the GOALS sample is extremely high, with a median value (3.9*10^{-10} yr^{-1}) that is comparable to the highest specific star formation rates seen in the Spitzer Infrared Nearby Galaxies Survey sample. We examine the position of each galaxy on the IR excess-UV slope (IRX-beta) diagram as a function of galaxy properties, including IR luminosity and interaction stage. The LIRGs on average have greater IR excesses than would be expected based on their UV colors if they obeyed the same relations as starbursts with L_IR < 10^{11}L_0 or normal late-type galaxies. The ratio of L_IR to the value one would estimate from the IRXg-beta relation published for lower luminosity starburst galaxies ranges from 0.2 to 68, with a median value of 2.7. A minimum of 19% of the total IR luminosity in the RBGS is produced in LIRGs and ULIRGs with red UV colors (beta > 0). Among resolved interacting systems, 32% contain one galaxy which dominates the IR emission while the companion dominates the UV emission. Only 21% of the resolved systems contain a single galaxy which dominates both wavelengths.Comment: 37 pages, 10 figures, accepted for publication in Ap

Tracing PAHs and Warm Dust Emission in the Seyfert Galaxy NGC 1068

We present a study of the nearby Seyfert galaxy NGC 1068 using mid- and far- infrared data acquired with the IRAC, IRS, and MIPS instruments aboard the Spitzer Space Telescope. The images show extensive 8 um and 24 um emission coinciding with star formation in the inner spiral approximately 15" (1 kpc) from the nucleus, and a bright complex of star formation 47" (3 kpc) SW of the nucleus. The brightest 8 um PAH emission regions coincide remarkably well with knots observed in an Halpha image. Strong PAH features at 6.2, 7.7, 8.6, and 11.3 um are detected in IRS spectra measured at numerous locations inside, within, and outside the inner spiral. The IRAC colors and IRS spectra of these regions rule out dust heated by the AGN as the primary emission source; the SEDs are dominated by starlight and PAH emission. The equivalent widths and flux ratios of the PAH features in the inner spiral are generally consistent with conditions in a typical spiral galaxy ISM. Interior to the inner spiral, the influence of the AGN on the ISM is evident via PAH flux ratios indicative of a higher ionization parameter and a significantly smaller mean equivalent width than observed in the inner spiral. The brightest 8 and 24 um emission peaks in the disk of the galaxy, even at distances beyond the inner spiral, are located within the ionization cones traced by [O III]/Hbeta, and they are also remarkably well aligned with the axis of the radio jets. Although it is possible that radiation from the AGN may directly enhance PAH excitation or trigger the formation of OB stars that subsequently excite PAH emission at these locations in the inner spiral, the orientation of collimated radiation from the AGN and star formation knots in the inner spiral could be coincidental. (abridged)Comment: 20 pages, 11 figures; AJ, accepted; full resolution version available at http://spider.ipac.caltech.edu/staff/jhhowell/astro/howelln1068.pd

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

In Search of Cellular Immunophenotypes in the Blood of Children with Autism

Autism is a neurodevelopmental disorder characterized by impairments in social behavior, communication difficulties and the occurrence of repetitive or stereotyped behaviors. There has been substantial evidence for dysregulation of the immune system in autism.We evaluated differences in the number and phenotype of circulating blood cells in young children with autism (n = 70) compared with age-matched controls (n = 35). Children with a confirmed diagnosis of autism (4-6 years of age) were further subdivided into low (IQ<68, n = 35) or high functioning (IQ ≥ 68, n = 35) groups. Age- and gender-matched typically developing children constituted the control group. Six hundred and forty four primary and secondary variables, including cell counts and the abundance of cell surface antigens, were assessed using microvolume laser scanning cytometry.There were multiple differences in immune cell populations between the autism and control groups. The absolute number of B cells per volume of blood was over 20% higher for children with autism and the absolute number of NK cells was about 40% higher. Neither of these variables showed significant difference between the low and high functioning autism groups. While the absolute number of T cells was not different across groups, a number of cellular activation markers, including HLA-DR and CD26 on T cells, and CD38 on B cells, were significantly higher in the autism group compared to controls.These results support previous findings that immune dysfunction may occur in some children with autism. Further evaluation of the nature of the dysfunction and how it may play a role in the etiology of autism or in facets of autism neuropathology and/or behavior are needed

An Integrative Multi-Network and Multi-Classifier Approach to Predict Genetic Interactions

Genetic interactions occur when a combination of mutations results in a surprising phenotype. These interactions capture functional redundancy, and thus are important for predicting function, dissecting protein complexes into functional pathways, and exploring the mechanistic underpinnings of common human diseases. Synthetic sickness and lethality are the most studied types of genetic interactions in yeast. However, even in yeast, only a small proportion of gene pairs have been tested for genetic interactions due to the large number of possible combinations of gene pairs. To expand the set of known synthetic lethal (SL) interactions, we have devised an integrative, multi-network approach for predicting these interactions that significantly improves upon the existing approaches. First, we defined a large number of features for characterizing the relationships between pairs of genes from various data sources. In particular, these features are independent of the known SL interactions, in contrast to some previous approaches. Using these features, we developed a non-parametric multi-classifier system for predicting SL interactions that enabled the simultaneous use of multiple classification procedures. Several comprehensive experiments demonstrated that the SL-independent features in conjunction with the advanced classification scheme led to an improved performance when compared to the current state of the art method. Using this approach, we derived the first yeast transcription factor genetic interaction network, part of which was well supported by literature. We also used this approach to predict SL interactions between all non-essential gene pairs in yeast (http://sage.fhcrc.org/downloads/downloads/predicted_yeast_genetic_interactions.zip). This integrative approach is expected to be more effective and robust in uncovering new genetic interactions from the tens of millions of unknown gene pairs in yeast and from the hundreds of millions of gene pairs in higher organisms like mouse and human, in which very few genetic interactions have been identified to date

Mesenteric Resistance Arteries in Type 2 Diabetic db/db Mice Undergo Outward Remodeling

Resistance vessel remodeling is controlled by myriad of hemodynamic and neurohormonal factors. This study characterized structural and molecular remodeling in mesenteric resistance arteries (MRAs) in diabetic (db/db) and control (Db/db) mice.Structural properties were assessed in isolated MRAs from 12 and 16 wk-old db/db and Db/db mice by pressure myography. Matrix regulatory proteins were measured by Western blot analysis. Mean arterial pressure and superior mesenteric blood flow were measured in 12 wk-old mice by telemetry and a Doppler flow nanoprobe, respectively.Blood pressure was similar between groups. Lumen diameter and medial cross-sectional area were significantly increased in 16 wk-old db/db MRA compared to control, indicating outward hypertrophic remodeling. Moreover, wall stress and cross-sectional compliance were significantly larger in diabetic arteries. These remodeling indices were associated with increased expression of matrix regulatory proteins matrix metalloproteinase (MMP)-9, MMP-12, tissue inhibitors of matrix metalloproteinase (TIMP)-1, TIMP-2, and plasminogen activator inhibitor-1 (PAI-1) in db/db arteries. Finally, superior mesenteric artery blood flow was increased by 46% in 12 wk-old db/db mice, a finding that preceded mesenteric resistance artery remodeling.These data suggest that flow-induced hemodynamic changes may supersede the local neurohormonal and metabolic milieu to culminate in hypertrophic outward remodeling of type 2 DM mesenteric resistance arteries

Genomic and epigenetic evidence for oxytocin receptor deficiency in autism

<p>Abstract</p> <p>Background</p> <p>Autism comprises a spectrum of behavioral and cognitive disturbances of childhood development and is known to be highly heritable. Although numerous approaches have been used to identify genes implicated in the development of autism, less than 10% of autism cases have been attributed to single gene disorders.</p> <p>Methods</p> <p>We describe the use of high-resolution genome-wide tilepath microarrays and comparative genomic hybridization to identify copy number variants within 119 probands from multiplex autism families. We next carried out DNA methylation analysis by bisulfite sequencing in a proband and his family, expanding this analysis to methylation analysis of peripheral blood and temporal cortex DNA of autism cases and matched controls from independent datasets. We also assessed oxytocin receptor (OXTR) gene expression within the temporal cortex tissue by quantitative real-time polymerase chain reaction (PCR).</p> <p>Results</p> <p>Our analysis revealed a genomic deletion containing the oxytocin receptor gene, <it>OXTR </it>(MIM accession no.: 167055), previously implicated in autism, was present in an autism proband and his mother who exhibits symptoms of obsessive-compulsive disorder. The proband's affected sibling did not harbor this deletion but instead may exhibit epigenetic misregulation of this gene through aberrant gene silencing by DNA methylation. Further DNA methylation analysis of the CpG island known to regulate <it>OXTR </it>expression identified several CpG dinucleotides that show independent statistically significant increases in the DNA methylation status in the peripheral blood cells and temporal cortex in independent datasets of individuals with autism as compared to control samples. Associated with the increase in methylation of these CpG dinucleotides is our finding that <it>OXTR </it>mRNA showed decreased expression in the temporal cortex tissue of autism cases matched for age and sex compared to controls.</p> <p>Conclusion</p> <p>Together, these data provide further evidence for the role of OXTR and the oxytocin signaling pathway in the etiology of autism and, for the first time, implicate the epigenetic regulation of <it>OXTR </it>in the development of the disorder.</p> <p>See the related commentary by Gurrieri and Neri: <url>http://www.biomedcentral.com/1741-7015/7/63</url></p

Evaluating the Immune Response in Treatment-Naive Hospitalised Patients With Influenza and COVID-19

The worldwide COVID-19 pandemic has claimed millions of lives and has had a profound effect on global life. Understanding the body’s immune response to SARS-CoV-2 infection is crucial in improving patient management and prognosis. In this study we compared influenza and SARS-CoV-2 infected patient cohorts to identify distinct blood transcript abundances and cellular composition to better understand the natural immune response associated with COVID-19, compared to another viral infection being influenza, and identify a prognostic signature of COVID-19 patient outcome. Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of 88 patients infected with influenza and a cohort of 80 patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines. Gene transcript abundances, enriched pathways and cellular composition were compared between cohorts using RNA-seq. A genetic signature between COVID-19 survivors and non-survivors was assessed as a prognostic predictor of COVID-19 outcome. Contrasting immune responses were detected with an innate response elevated in influenza and an adaptive response elevated in COVID-19. Additionally ribosomal, mitochondrial oxidative stress and interferon signalling pathways differentiated the cohorts. An adaptive immune response was associated with COVID-19 survival, while an inflammatory response predicted death. A prognostic transcript signature, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, was able to stratify COVID-19 patients likely to survive or die. This study provides a unique insight into the immune responses of treatment naïve patients with influenza or COVID-19. The comparison of immune response between COVID-19 survivors and non-survivors enables prognostication of COVID-19 patients and may suggest potential therapeutic strategies to improve survival