McNair Research Journal - Summer 2015

Journal articles based on research conducted by undergraduate students in the McNair Scholars Program Table of Contents Biography of Dr. Ronald E. McNair Statements: Dr. Neal J. Smatresk, UNLV President Dr. Juanita P. Fain, Vice President of Student Affairs Dr. William W. Sullivan, Associate Vice President for Retention and Outreach Mr. Keith Rogers, Deputy Executive Director of the Center for Academic Enrichment and Outreach McNair Scholars Institute Staf

Isoprene emission structures tropical tree biogeography and community assembly responses to climate.

The prediction of vegetation responses to climate requires a knowledge of how climate-sensitive plant traits mediate not only the responses of individual plants, but also shifts in the species and functional compositions of whole communities. The emission of isoprene gas – a trait shared by one-third of tree species – is known to protect leaf biochemistry under climatic stress. Here, we test the hypothesis that isoprene emission shapes tree species compositions in tropical forests by enhancing the tolerance of emitting trees to heat and drought. Using forest inventory data, we estimated the proportional abundance of isoprene-emitting trees (pIE) at 103 lowland tropical sites. We also quantified the temporal composition shifts in three tropical forests – two natural and one artificial – subjected to either anomalous warming or drought. Across the landscape, pIE increased with site mean annual temperature, but decreased with dry season length. Through time, pIE strongly increased under high temperatures, and moderately increased following drought. Our analysis shows that isoprene emission is a key plant trait determining species responses to climate. For species adapted to seasonal dry periods, isoprene emission may tradeoff with alternative strategies, such as leaf deciduousness. Community selection for isoprene-emitting species is a potential mechanism for enhanced forest resilience to climatic change.Financial support for this study was provided to: T.C.T. and S.R.S. by grants NSF-PIRE #OISE-0730305, USDOE #3002937712, NASA #NNX17AF65G and the University of AZ Agnes Nelms Haury Program in Environment and Social Justice; to M.N.S. and S.R.S. by NASA-ESSF #NNX14AK95H; to C.V. by ERCStG-2014-639706-CONSTRAINTS; to I.S. by Grant Agency of the Czech Republic #16-26369S; and to P.M. by NERC # NE/ N006852/1 and ARC #DP170104091

The consolidated European synthesis of CH4 and N2O emissions for the European Union and United Kingdom : 1990-2017

Reliable quantification of the sources and sinks of greenhouse gases, together with trends and uncertainties, is essential to monitoring the progress in mitigating anthropogenic emissions under the Paris Agreement. This study provides a consolidated synthesis of CH4 and N2O emissions with consistently derived state-of-the-art bottom-up (BU) and top-down (TD) data sources for the European Union and UK (EU27 C UK). We integrate recent emission inventory data, ecosystem process-based model results and inverse modeling estimates over the period 1990-2017. BU and TD products are compared with European national greenhouse gas inventories (NGHGIs) reported to the UN climate convention UNFCCC secretariat in 2019. For uncertainties, we used for NGHGIs the standard deviation obtained by varying parameters of inventory calculations, reported by the member states (MSs) following the recommendations of the IPCC Guidelines. For atmospheric inversion models (TD) or other inventory datasets (BU), we defined uncertainties from the spread between different model estimates or model-specific uncertainties when reported. In comparing NGHGIs with other approaches, a key source of bias is the activities included, e.g., anthropogenic versus anthropogenic plus natural fluxes. In inversions, the separation between anthropogenic and natural emissions is sensitive to the geospatial prior distribution of emissions. Over the 2011-2015 period, which is the common denominator of data availability between all sources, the anthropogenic BU approaches are directly comparable, reporting mean emissions of 20.8 TgCH(4) yr (-1) (EDGAR v5.0) and 19.0 TgCH(4) yr(-1) (GAINS), consistent with the NGHGI estimates of 18.9 +/- 1.7 TgCH(4) yr(-1). The estimates of TD total inversions give higher emission estimates, as they also include natural emissions. Over the same period regional TD inversions with higher-resolution atmospheric transport models give a mean emission of 28.8 TgCH(4) yr(-1). Coarser-resolution global TD inversions are consistent with regional TD inversions, for global inversions with GOSAT satellite data (23.3 TgCH(4) yr(-1)) and surface network (24.4 TgCH(4) yr (-1)). The magnitude of natural peatland emissions from the JSBACH-HIMMELI model, natural rivers and lakes emissions, and geological sources together account for the gap between NGHGIs and inversions and account for 5.2 TgCH(4) yr(-1). For N2O emissions, over the 2011-2015 period, both BU approaches (EDGAR v5.0 and GAINS) give a mean value of anthropogenic emissions of 0.8 and 0.9 TgN(2)Oyr(-1), respectively, agreeing with the NGHGI data (0.9 0.6 TgN(2)Oyr(-1)). Over the same period, the average of the three total TD global and regional inversions was 1.3 +/- 0.4 and 1.3 +/- 0.1 TgN(2)Oyr(-1), respectively. The TD and BU comparison method defined in this study can be operationalized for future yearly updates for the calculation of CH4 and N2O budgets both at the EU CUK scale and at the national scale.Peer reviewe

The Varicella-Zoster Virus ORF47 Kinase Interferes with Host Innate Immune Response by Inhibiting the Activation of IRF3

The innate immune response constitutes the first line of host defence that limits viral spread and plays an important role in the activation of adaptive immune response. Viral components are recognized by specific host pathogen recognition receptors triggering the activation of IRF3. IRF3, along with NF-κB, is a key regulator of IFN-β expression. Until now, the role of IRF3 in the activation of the innate immune response during Varicella-Zoster Virus (VZV) infection has been poorly studied. In this work, we demonstrated for the first time that VZV rapidly induces an atypical phosphorylation of IRF3 that is inhibitory since it prevents subsequent IRF3 homodimerization and induction of target genes. Using a mutant virus unable to express the viral kinase ORF47p, we demonstrated that (i) IRF3 slower-migrating form disappears; (ii) IRF3 is phosphorylated on serine 396 again and recovers the ability to form homodimers; (iii) amounts of IRF3 target genes such as IFN-β and ISG15 mRNA are greater than in cells infected with the wild-type virus; and (iv) IRF3 physically interacts with ORF47p. These data led us to hypothesize that the viral kinase ORF47p is involved in the atypical phosphorylation of IRF3 during VZV infection, which prevents its homodimerization and subsequent induction of target genes such as IFN-β and ISG15

The consolidated European synthesis of CH4 and N2O emissions for the European Union and United Kingdom : 1990-2019

Funding Information: We thank Aurélie Paquirissamy, Géraud Moulas and the ARTTIC team for the great managerial support offered during the project. FAOSTAT statistics are produced and disseminated with the support of its member countries to the FAO regular budget. Annual, gap-filled and harmonized NGHGI uncertainty estimates for the EU and its member states were provided by the EU GHG inventory team (European Environment Agency and its European Topic Centre on Climate change mitigation). Most top-down inverse simulations referred to in this paper rely for the derivation of optimized flux fields on observational data provided by surface stations that are part of networks like ICOS (datasets: 10.18160/P7E9-EKEA , Integrated Non-CO Observing System, 2018a, and 10.18160/B3Q6-JKA0 , Integrated Non-CO Observing System, 2018b), AGAGE, NOAA (Obspack Globalview CH: 10.25925/20221001 , Schuldt et al., 2017), CSIRO and/or WMO GAW. We thank all station PIs and their organizations for providing these valuable datasets. We acknowledge the work of other members of the EDGAR group (Edwin Schaaf, Jos Olivier) and the outstanding scientific contribution to the VERIFY project of Peter Bergamaschi. Timo Vesala thanks ICOS-Finland, University of Helsinki. The TM5-CAMS inversions are available from https://atmosphere.copernicus.eu (last access: June 2022); Arjo Segers acknowledges support from the Copernicus Atmosphere Monitoring Service, implemented by the European Centre for Medium-Range Weather Forecasts on behalf of the European Commission (grant no. CAMS2_55). This research has been supported by the European Commission, Horizon 2020 Framework Programme (VERIFY, grant no. 776810). Ronny Lauerwald received support from the CLand Convergence Institute. Prabir Patra received support from the Environment Research and Technology Development Fund (grant no. JPMEERF20182002) of the Environmental Restoration and Conservation Agency of Japan. Pierre Regnier received financial support from the H2020 project ESM2025 – Earth System Models for the Future (grant no. 101003536). David Basviken received support from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (METLAKE, grant no. 725546). Greet Janssens-Maenhout received support from the European Union's Horizon 2020 research and innovation program (CoCO, grant no. 958927). Tuula Aalto received support from the Finnish Academy (grants nos. 351311 and 345531). Sönke Zhaele received support from the ERC consolidator grant QUINCY (grant no. 647204).Peer reviewedPublisher PD

A Cryogenic Silicon Interferometer for Gravitational-wave Detection

The detection of gravitational waves from compact binary mergers by LIGO has opened the era of gravitational wave astronomy, revealing a previously hidden side of the cosmos. To maximize the reach of the existing LIGO observatory facilities, we have designed a new instrument able to detect gravitational waves at distances 5 times further away than possible with Advanced LIGO, or at greater than 100 times the event rate. Observations with this new instrument will make possible dramatic steps toward understanding the physics of the nearby Universe, as well as observing the Universe out to cosmological distances by the detection of binary black hole coalescences. This article presents the instrument design and a quantitative analysis of the anticipated noise floor

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049