Student Recital (December 7, 2015)

Choro de Saudade / Agustin Barrios Mangore Nolan Driscoll, guitar My mother bids me bind my hair / Franz Josef Haydn Willow Song (The Ballad of Baby Doe) / Douglas Moore Elizabeth Lach, soprano Thoughts of Love / Arthur Pryor I. Tempo di valse II. Tempo di valse III. Tempo di valse Nicholas Grisolia, euphonium Che gelida manina (La Boheme) / Giacomo Puccini Richard Moran, tenor Sonata 5 in F Major, Opus 24 / Ludwig van Beethoven Allegro Megan Polk, violin O vos omnes (The Seven Last Words of Christ) / Theodore Dubois Colleen McDonough, soprano Hommage a Villa-Lobos / Roland Dyens Andantinostalgie Tuhu Austin DeAndrade, guitar Morgen, Opus 21, No. 4 / Richard Strauss Justine Smigel, soprano Nature beyond art / Thomas Arne Xavier Cosme, tenor Violin Concerto No. 3 in G Major, K. 216 / W. A. Mozart Allegro Gail Colombo, violin Yu Guang Qu (Song of the Fisherman) / Guang Ran Jiaying Zhu, soprano El Decameron Negro / Leo Brouwer El arpa del guerrero Killian Kerrigan, guitar Una donna quindici anni (Cosi fan tutte), K. 588 / Wolfgang Amadeus Mozart Angela Maloney, soprano Concert Etude, Opus 49 / Alexander Goedicke Lindsey Cook, trumpethttps://vc.bridgew.edu/student_concerts/1101/thumbnail.jp

Seminaphthofluorescein-Based Fluorescent Probes for Imaging Nitric Oxide in Live Cells

Fluorescent turn-on probes for nitric oxide based on seminaphthofluorescein scaffolds were prepared and spectroscopically characterized. The Cu(II) complexes of these fluorescent probes react with NO under anaerobic conditions to yield a 20–45-fold increase in integrated emission. The seminaphthofluorescein-based probes emit at longer wavelengths than the parent FL1 and FL2 fluorescein-based generations of NO probes, maintaining emission maxima between 550 and 625 nm. The emission profiles depend on the excitation wavelength; maximum fluorescence turn-on is achieved at excitations between 535 and 575 nm. The probes are highly selective for NO over other biologically relevant reactive nitrogen and oxygen species including NO3–, NO2–, HNO, ONOO–, NO2, OCl–, and H2O2. The seminaphthofluorescein-based probes can be used to visualize endogenously produced NO in live cells, as demonstrated using Raw 264.7 macrophages.National Science Foundation (U.S.) (CHE-0611944)National Institutes of Health (U.S.) (K99GM092970

Pharmacological Targeting of Native CatSper Channels Reveals a Required Role in Maintenance of Sperm Hyperactivation

The four sperm-specific CatSper ion channel proteins are required for hyperactivated motility and male fertility, and for Ca2+ entry evoked by alkaline depolarization. In the absence of external Ca2+, Na+ carries current through CatSper channels in voltage-clamped sperm. Here we show that CatSper channel activity can be monitored optically with the [Na+]i-reporting probe SBFI in populations of intact sperm. Removal of external Ca2+ increases SBFI signals in wild-type but not CatSper2-null sperm. The rate of the indicated rise of [Na+]i is greater for sperm alkalinized with NH4Cl than for sperm acidified with propionic acid, reflecting the alkaline-promoted signature property of CatSper currents. In contrast, the [Na+]i rise is slowed by candidate CatSper blocker HC-056456 (IC50 ∼3 µM). HC-056456 similarly slows the rise of [Ca2+]i that is evoked by alkaline depolarization and reported by fura-2. HC-056456 also selectively and reversibly decreased CatSper currents recorded from patch-clamped sperm. HC-056456 does not prevent activation of motility by HCO3− but does prevent the development of hyperactivated motility by capacitating incubations, thus producing a phenocopy of the CatSper-null sperm. When applied to hyperactivated sperm, HC-056456 causes a rapid, reversible loss of flagellar waveform asymmetry, similar to the loss that occurs when Ca2+ entry through the CatSper channel is terminated by removal of external Ca2+. Thus, open CatSper channels and entry of external Ca2+ through them sustains hyperactivated motility. These results indicate that pharmacological targeting of the CatSper channel may impose a selective late-stage block to fertility, and that high-throughput screening with an optical reporter of CatSper channel activity may identify additional selective blockers with potential for male-directed contraception

Citizen-Science for the Future: Advisory Case Studies From Around the Globe

The democratization of ocean observation has the potential to add millions of observations every day. Though not a solution for all ocean monitoring needs, citizen scientists offer compelling examples showcasing their ability to augment and enhance traditional research and monitoring. Information they are providing is increasing the spatial and temporal frequency and duration of sampling, reducing time and labor costs for academic and government monitoring programs, providing hands-on STEM learning related to real-world issues and increasing public awareness and support for the scientific process. Examples provided here demonstrate the wide range of people who are already dramatically reducing gaps in our global observing network while at the same time providing unique opportunities to meaningfully engage in ocean observing and the research and conservation it supports. While there are still challenges to overcome before widespread inclusion in projects requiring scientific rigor, the growing organization of international citizen science associations is helping to reduce barriers. The case studies described support the idea that citizen scientists should be part of an effective global strategy for a sustained, multidisciplinary and integrated observing system

Complement genes contribute sex-biased vulnerability in diverse disorders.

Many common illnesses, for reasons that have not been identified, differentially affect men and women. For instance, the autoimmune diseases systemic lupus erythematosus (SLE) and Sjögren's syndrome affect nine times more women than men1, whereas schizophrenia affects men with greater frequency and severity relative to women2. All three illnesses have their strongest common genetic associations in the major histocompatibility complex (MHC) locus, an association that in SLE and Sjögren's syndrome has long been thought to arise from alleles of the human leukocyte antigen (HLA) genes at that locus3-6. Here we show that variation of the complement component 4 (C4) genes C4A and C4B, which are also at the MHC locus and have been linked to increased risk for schizophrenia7, generates 7-fold variation in risk for SLE and 16-fold variation in risk for Sjögren's syndrome among individuals with common C4 genotypes, with C4A protecting more strongly than C4B in both illnesses. The same alleles that increase risk for schizophrenia greatly reduce risk for SLE and Sjögren's syndrome. In all three illnesses, C4 alleles act more strongly in men than in women: common combinations of C4A and C4B generated 14-fold variation in risk for SLE, 31-fold variation in risk for Sjögren's syndrome, and 1.7-fold variation in schizophrenia risk among men (versus 6-fold, 15-fold and 1.26-fold variation in risk among women, respectively). At a protein level, both C4 and its effector C3 were present at higher levels in cerebrospinal fluid and plasma8,9 in men than in women among adults aged between 20 and 50 years, corresponding to the ages of differential disease vulnerability. Sex differences in complement protein levels may help to explain the more potent effects of C4 alleles in men, women's greater risk of SLE and Sjögren's syndrome and men's greater vulnerability to schizophrenia. These results implicate the complement system as a source of sexual dimorphism in vulnerability to diverse illnesses

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Evolution of a Compound Channel: Tassajara Creek, Dublin, California

Between 1960 and 1990, Tassajara Creek in Dublin, CA underwent incision due to anthropogenic sources. The downcutting of the channel bottom was problematic because the process built upon itself and caused disconnection between the channel and floodplain. The incision of Tassajara Creek created a flooding problem and motivated the search for solutions. The need for flood control increased as development increased around the creek. During the 1990s, plans were made to restore Tassajara Creek and provide flood control through the creation of a compound channel. In addition to drainage, the restoration plan’s secondary goals were to increase vegetation, riparian habitat, and public access. A one-mile reach of Tassajara Creek was reconstructed in 1999 and a series of post project appraisals have been conducted since with mixed results. We reviewed and summarized the results of the past studies. We continued the monitoring of the channel evolution by resurveying three of the established cross sections and a partial long profile and compared our data to previous data sets. We also conducted a qualitative analysis of the project’s secondary goals by through observations and photograph comparisons. Our survey data indicated that deposition was occurring on the majority of the floodplain. The channel bottom evolved differently between cross-sections. We found instances of local incision for the most upstream cross-section, E-E’. The channel bottom for the more downstream cross-sections F-F’ and G-G’ aggraded especially at G-G’ where dense cattails encouraged aggradation in the channel. We concluded from a comparison to previous data that the channel is still actively evolving since there was no clear trend towards either incision or aggradation. Our comparison of previous with current photographs showed an increase in vegetation since 2004. The further downstream reach had a lot of diverse vegetation which provided habitat for macroinvertebrates. We concluded the secondary goals were well achieved with a significant increase in the amount of vegetation and habitat with a healthy population of macro-invertebrates