Observations of Arp 220 using Herschel-SPIRE: An Unprecedented View of the Molecular Gas in an Extreme Star Formation Environment

We present Herschel SPIRE-FTS observations of Arp~220, a nearby ULIRG. The FTS continuously covers 190 -- 670 microns, providing a good measurement of the continuum and detection of several molecular and atomic species. We detect luminous CO (J = 4-3 to 13-12) and water ladders with comparable total luminosity; very high-J HCN absorption; OH+, H2O+, and HF in absorption; and CI and NII. Modeling of the continuum yields warm dust, with T = 66 K, and an unusually large optical depth of ~5 at 100 microns. Non-LTE modeling of the CO shows two temperature components: cold molecular gas at T ~ 50 K and warm molecular gas at T ~1350 K. The mass of the warm gas is 10% of the cold gas, but dominates the luminosity of the CO ladder. The temperature of the warm gas is in excellent agreement with H2 rotational lines. At 1350 K, H2 dominates the cooling (~20 L_sun/M_sun) in the ISM compared to CO (~0.4 L_sun/M_sun). We found that only a non-ionizing source such as the mechanical energy from supernovae and stellar winds can excite the warm gas and satisfy the energy budget of ~20 L_sun/M_sun. We detect a massive molecular outflow in Arp 220 from the analysis of strong P-Cygni line profiles observed in OH+, H2O+, and H2O. The outflow has a mass > 10^{7} M_sun and is bound to the nuclei with velocity < 250 km/s. The large column densities observed for these molecular ions strongly favor the existence of an X-ray luminous AGN (10^{44} ergs/s) in Arp 220.Comment: Accepted in ApJ on September 1, 201

A deep learning approach to photo–identification demonstrates high performance on two dozen cetacean species

We thank the countless individuals who collected and/or processed the nearly 85,000 images used in this study and those who assisted, particularly those who sorted these images from the millions that did not end up in the catalogues. Additionally, we thank the other Kaggle competitors who helped develop the ideas, models and data used here, particularly those who released their datasets to the public. The graduate assistantship for Philip T. Patton was funded by the NOAA Fisheries QUEST Fellowship. This paper represents HIMB and SOEST contribution numbers 1932 and 11679, respectively. The technical support and advanced computing resources from University of Hawaii Information Technology Services—Cyberinfrastructure, funded in part by the National Science Foundation CC* awards # 2201428 and # 2232862 are gratefully acknowledged. Every photo–identification image was collected under permits according to relevant national guidelines, regulation and legislation.Peer reviewedPublisher PD

Frequency of LATE neuropathologic change across the spectrum of Alzheimer’s disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer’s disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese–American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia—broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with “frequent” neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer’s disease neuropathology

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Microorganisms from sand, cloacal fluid, and eggs of Lepidochelys olivacea and standard testing of cloacal fluid antimicrobial properties

Microorganisms associated with olive ridley nesting and potential antimicrobial properties of cloacal fluid were studied at Parque Nacional Marino las Baulas, Costa Rica, and nearby beaches during the 2010-2011 and 2011-2012 seasons. During the first season, bacteria and fungi were isolated and identified from frozen nest chamber sand, cloacal fluid, and unhatched egg samples. This first season, fungi were isolated from cloacal fluid samples, but bacteria were not, however, bacteria and fungi were both isolated from sand and unhatched egg samples. Enterobacter cloacae and Pseudomonas aeruginosa were the most common unhatched egg bacterial isolates. All fungal genera isolated from unhatched eggs had been isolated in previous studies, but this was the first study were Cladosporium was isolated from olive ridley egg chamber sand, and were Aspergillus, Cladosporium, Penicillium, and Geotrichum were isolated from olive ridley cloacal fluid. Prior to this study, Geotrichum had not been associated with nesting sea turtles. The second season, samples were not frozen to determine if cloacal fluid contains bacteria, which may have been lost due to freezing the first season, and to identify any potential sand bacterial contaminants in the cloacal fluid. These unfrozen cloacal fluid samples contained Corynebacterium sp., Bacillus sp., Klebsiella sp., as well as genera documented in previous studies. Citrobacter freundii and Serratia odorifera were common in both the cloacal fluid and nest chamber sand samples on all beaches, thus may be potential sand contaminants of cloacal fluid. Kirby-Bauer disk diffusion assays could not detect antimicrobial properties of cloacal fluid against E. cloacae, P. aeruginosa, and Staphylococcus aureus control strains for both olive ridleys and a few opportunistically sampled Eastern Pacific green turtles (Chelonia mydas agassizii). While we cannot say cloacal fluid antimicrobial properties are absent against our test organisms, it is clear they are neither abundant nor widespread in these nesting populations

Segmental duplications mediate novel, clinically relevant chromosome rearrangements

Copy number studies have led to an explosion in the discovery of new segmental duplication-mediated deletions and duplications. We have analyzed copy number changes in 2419 patients referred for clinical array comparative genomic hybridization studies. Twenty-three percent of the abnormal copy number changes we found are immediately flanked by segmental duplications ≥10 kb in size and ≥95% identical in direct orientation, consistent with deletions and duplications generated by non-allelic homologous recombination. Here, we describe copy number changes in five previously unreported loci with genomic organization characteristic of NAHR-mediated gains and losses; namely, 2q11.2, 7q36.1, 17q23, 2q13 and 7q11.21. Deletions and duplications of 2q11.2, deletions of 7q36.1 and deletions of 17q23 are interpreted as pathogenic based on their genomic size, gene content, de novo inheritance and absence from control populations. The clinical significance of 2q13 deletions and duplications is still emerging, as these imbalances are also found in phenotypically normal family members and control individuals. Deletion of 7q11.21 is a benign copy number change well represented in control populations and copy number variation databases. Here, we discuss the genetic factors that can modify the phenotypic expression of such gains and losses, which likely play a role in these and other recurrent genomic disorders

"How Do We Do This at a Distance?!" A Descriptive Study of Remote Undergraduate Research Programs during COVID-19.

The COVID-19 pandemic shut down undergraduate research programs across the United States. A group of 23 colleges, universities, and research institutes hosted remote undergraduate research programs in the life sciences during Summer 2020. Given the unprecedented offering of remote programs, we carried out a study to describe and evaluate them. Using structured templates, we documented how programs were designed and implemented, including who participated. Through focus groups and surveys, we identified programmatic strengths and shortcomings as well as recommendations for improvements from students' perspectives. Strengths included the quality of mentorship, opportunities for learning and professional development, and a feeling of connection with a larger community. Weaknesses included limited cohort building, challenges with insufficient structure, and issues with technology. Although all programs had one or more activities related to diversity, equity, inclusion, and justice, these topics were largely absent from student reports even though programs coincided with a peak in national consciousness about racial inequities and structural racism. Our results provide evidence for designing remote Research Experiences for Undergraduates (REUs) that are experienced favorably by students. Our results also indicate that remote REUs are sufficiently positive to further investigate their affordances and constraints, including the potential to scale up offerings, with minimal concern about disenfranchising students