Digital Commons Network^™

High-Coverage Whole-Genome Sequencing Of The Expanded 1000 Genomes Project Cohort Including 602 Trios, Marta Byrska-Bishop, Haley J Abel, Allison A Regier, Ira M Hall, Et Al.

2020-Current year OA Pubs

The 1000 Genomes Project (1kGP) is the largest fully open resource of whole-genome sequencing (WGS) data consented for public distribution without access or use restrictions. The final, phase 3 release of the 1kGP included 2,504 unrelated samples from 26 populations and was based primarily on low-coverage WGS. Here, we present a high-coverage 3,202-sample WGS 1kGP resource, which now includes 602 complete trios, sequenced to a depth of 30X using Illumina. We performed single-nucleotide variant (SNV) and short insertion and deletion (INDEL) discovery and generated a comprehensive set of structural variants (SVs) by integrating multiple analytic methods through a machine learning …

An Ips-Derived In Vitro Model Of Human Atrial Conduction, Sherri M Biendarra-Tiegs, Sergey Yechikov, Bhupinder Shergill, Brittany Brumback, Kentaro Takahashi, Venktesh S Shirure, Ruth Estelle Gonzalez, Laura Houshmand, Denise Zhong, Kuo-Chan Weng, Jon Silva, Timothy W Smith, Stacey L Rentschler, Steven C George

2020-Current year OA Pubs

Atrial fibrillation (AF) is the most common arrhythmia in the United States, affecting approximately 1 in 10 adults, and its prevalence is expected to rise as the population ages. Treatment options for AF are limited; moreover, the development of new treatments is hindered by limited (1) knowledge regarding human atrial electrophysiological endpoints (e.g., conduction velocity [CV]) and (2) accurate experimental models. Here, we measured the CV and refractory period, and subsequently calculated the conduction wavelength, in vivo (four subjects with AF and four controls), and ex vivo (atrial slices from human hearts). Then, we created an in vitro model of …

World Guidelines For Falls Prevention And Management For Older Adults: A Global Initiative, Manuel Montero-Odasso, Susan Stark, Et Al.

2020-Current year OA Pubs

No abstract provided.

Implications Of Conformational Flexibility, Lipid Binding, And Regulatory Domains In Cell-Traversal Protein Celtos For Apicomplexan Migration, Hirdesh Kumar, John R Jimah, Santosh A Misal, Nichole D Salinas, Michal Fried, Paul H Schlesinger, Niraj H Tolia

2020-Current year OA Pubs

Malaria and other apicomplexan-caused diseases affect millions of humans, agricultural animals, and pets. Cell traversal is a common feature used by multiple apicomplexan parasites to migrate through host cells and can be exploited to develop therapeutics against these deadly parasites. Here, we provide insights into the mechanism of the Cell-traversal protein for ookinetes and sporozoites (CelTOS), a conserved cell-traversal protein in apicomplexan parasites and malaria vaccine candidate. CelTOS has previously been shown to form pores in cell membranes to enable traversal of parasites through cells. We establish roles for the distinct protein regions of Plasmodium vivax CelTOS and examine the …

Dynamic S-Acylation Of The Er-Resident Protein Stromal Interaction Molecule 1 (Stim1) Is Required For Store-Operated Ca2+ Entry, Goutham Kodakandla, Savannah J West, Qiaochu Wang, Ritika Tewari, Michael X Zhu, Askar M Akimzhanov, Darren Boehning

Faculty, Staff and Student Publications

Many cell surface stimuli cause calcium release from endoplasmic reticulum (ER) stores to regulate cellular physiology. Upon ER calcium store depletion, the ER-resident protein stromal interaction molecule 1 (STIM1) physically interacts with plasma membrane protein Orai1 to induce calcium release-activated calcium (CRAC) currents that conduct calcium influx from the extracellular milieu. Although the physiological relevance of this process is well established, the mechanism supporting the assembly of these proteins is incompletely understood. Earlier we demonstrated a previously unknown post-translational modification of Orai1 with long-chain fatty acids, known as S-acylation. We found that S-acylation of Orai1 is dynamically regulated in a …

Accumulation Of Copy-Back Viral Genomes During Respiratory Syncytial Virus Infection Is Preceded By Diversification Of The Copy-Back Viral Genome Population Followed By Selection, Sébastien A Felt, Emna Achouri, Sydney R Faber, Carolina B López

2020-Current year OA Pubs

RNA viruses generate nonstandard viral genomes during their replication, including viral genomes of the copy-back (cbVGs) type that cannot replicate in the absence of a standard virus. cbVGs play a crucial role in shaping virus infection outcomes due to their ability to interfere with virus replication and induce strong immune responses. However, despite their critical role during infection, the principles that drive the selection and evolution of cbVGs within a virus population are poorly understood. As cbVGs are dependent on the virus replication machinery to be generated and replicated, we hypothesized that host factors that affect virus replication exert selective …

Measuring Transcription Factor Binding And Gene Expression Using Barcoded Self-Reporting Transposon Calling Cards And Transcriptomes, Matthew Lalli, Allen Yen, Urvashi Thopte, Fengping Dong, Arnav Moudgil, Xuhua Chen, Jeffrey Milbrandt, Joseph D Dougherty, Robi D Mitra

2020-Current year OA Pubs

Calling cards technology using self-reporting transposons enables the identification of DNA-protein interactions through RNA sequencing. Although immensely powerful, current implementations of calling cards in bulk experiments on populations of cells are technically cumbersome and require many replicates to identify independent insertions into the same genomic locus. Here, we have drastically reduced the cost and labor requirements of calling card experiments in bulk populations of cells by introducing a DNA barcode into the calling card itself. An additional barcode incorporated during reverse transcription enables simultaneous transcriptome measurement in a facile and affordable protocol. We demonstrate that barcoded self-reporting transposons recover

Pregnancy Outcomes Related To The Treatment Of Sarcomas With Anthracyclines And/Or Ifosfamide During Pregnancy, Devon Miller, John A Livingston, Yeonhee Park, Kristi Posey, Sonia Godbole, Keith Skubitz, Steven I Robinson, Mark Agulnik, Lara E Davis, Brian A Van Tine, Angela C Hirbe, Amanda Parkes

2020-Current year OA Pubs

BACKGROUND: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas.

PATIENTS AND METHODS: We conducted a multi-institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy. Chart review identified variables related to demographics, cancer diagnosis, therapies, and outcome of the patient and fetus. Wilcoxon rank-sum test compared two independent samples.

RESULTS: We identified 13 patients at seven institutions with sarcoma who received anthracyclines and/or ifosfamide during pregnancy, including four bone sarcomas and …

Disease Burden Affects Aging Brain Function, Lori L Beason-Held, Danielle Fournier, Andrea T Shafer, Elisa Fabbri, Yang An, Chiung-Wei Huang, Murat Bilgel, Dean F Wong, Luigi Ferrucci, Susan M Resnick

2020-Current year OA Pubs

BACKGROUND: Most older adults live with multiple chronic disease conditions, yet the effect of multiple diseases on brain function remains unclear.

METHODS: We examine the relationship between disease multimorbidity and brain activity using regional cerebral blood flow (rCBF) 15O-water PET scans from 97 cognitively normal participants (mean baseline age 76.5) in the Baltimore Longitudinal Study of Aging (BLSA). Multimorbidity index scores, generated from the presence of 13 health conditions, were correlated with PET data at baseline and in longitudinal change (n = 74) over 5.05 (2.74 SD) years.

RESULTS: At baseline, voxel-based analysis showed that higher multimorbidity scores were associated …

Tumor Immune Contexture Is A Determinant Of Anti-Cd19 Car T Cell Efficacy In Large B Cell Lymphoma, Nathalie Scholler, Armin Ghobadi, Et Al

2020-Current year OA Pubs

No abstract provided.

Real-World Evidence Of Axicabtagene Ciloleucel For The Treatment Of Large B Cell Lymphoma In The United States, Caron A Jacobson, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

Axicabtagene ciloleucel (axi-cel) is a standard-of-care for patients with relapsed or refractory (r/r) large B cell lymphoma who have received 2 or more lines of prior therapy. Patients receiving axi-cel in the real world could have broader a demographic, disease, and treatment profile compared with that of the cohort in the pivotal ZUMA-1 trial. The present study was conducted to evaluate the outcomes of axi-cel therapy in the real-world setting. A total of 1297 patients receiving commercial axi-cel between 2017 and 2020 were selected from the Center for International Blood and Marrow Transplant Research's data registry, of whom 739 (57%) …

Association Of Male Hypogonadism With Risk Of Hospitalization For Covid-19, Sandeep Dhindsa, Cosette Champion, Ekamjit Deol, Matthew Lui, Robert Campbell, Jennifer Newman, Aparna Yeggalam, Srikanth Nadella, Vaishaliben Ahir, Ekta Shrestha, Thomas Kannampallil, Abhinav Diwan

2020-Current year OA Pubs

Importance: Male sex is associated with severe COVID-19. It is not known whether the risk of hospitalization differs between men with hypogonadism, men with eugonadism, and those receiving testosterone therapy (TTh).

Objective: To compare COVID-19 hospitalization rates for men with hypogonadism who were not receiving TTh, men with eugonadism, and men receiving TTh.

Design, Setting, and Participants: This cohort study was conducted in 2 large academic health systems in St Louis, Missouri, among 723 men with a history of COVID-19 who had testosterone concentrations measured between January 1, 2017, and December 31, 2021.

Exposures: The primary exposure was gonadal status …

Coronary-To-Coronary Bypass Grafting In Aortoarteritis: A Case Report, Immaneni Sathyamurthy, Narra Lavanya, Kanthallu Narayanamoorthy Srinivasan, Maligail Ramkrishna Girinath

Faculty, Staff and Student Publications

Takayasu's arteritis (TA) is an idiopathic vasculitis affecting the aorta and its major branches. In TA, coronary artery involvement is rare and it mainly consists of stenosis or occlusion of the coronary ostia. In TA, as the arterial tree is diseased, often, arterial grafts are unsuitable for grafting so the saphenous vein grafts (SVG) are commonly used. We present a case of a young female with TA with an ostial left main stenosis who has undergone a right coronary-to-left anterior descending artery SVG and put on immunosuppression and steroids. She was asymptomatic with a patent graft during 7 years follow-up.

Apoptotic Brown Adipocytes Enhance Energy Expenditure Via Extracellular Inosine, Birte Niemann, Saskia Haufs-Brusberg, Laura Puetz, Martin Feickert, Michelle Y Jaeckstein, Anne Hoffmann, Jelena Zurkovic, Markus Heine, Eva-Maria Trautmann, Christa E Müller, Anke Tönjes, Christian Schlein, Azin Jafari, Holger K Eltzschig, Thorsten Gnad, Matthias Blüher, Natalie Krahmer, Peter Kovacs, Joerg Heeren, Alexander Pfeifer

Faculty, Staff and Student Publications

Brown adipose tissue (BAT) dissipates energy

A Key Study On Pollen-Specific Sfb Genotype And Identification Of Novel Sfb Alleles From 48 Accessions In Japanese Apricot (Prunus Mume Sieb. Et Zucc.), Daouda Coulibaly, Guofeng Hu, Zhaojun Ni, Kenneth Omondi Ouma, Xiao Huang, Shahid Iqbal, Chengdong Ma, Ting Shi, Faisal Hayat, Benjamin Karikari, Zhihong Gao

Michigan Tech Publications, Part 1

Self-incompatibility (SI) is a common strategy to avoid inbreeding and, consequently, keep genetic diversity within a species. In its mechanism, pollen rejection happens in the style when the single multiallelic locus (SFB in prunus species) of the haploid pollen matches one of the S-alleles existing in the diploid pistil. The SFB gene for the pollen S gene has been identified in many Prunus species. However, Japanese apricot is a species with a typical gametophytic self-incompatibility (GSI), and its SFB alleles available are limited, although they are required for studying GSI. Therefore, we used an AS-PCR amplification method, sequencing, and the …

Holy Simplicity: The Physician's Role In End-Of-Life Conversations, Joseph L. Williams, Benjamin Doolittle

Student Publications

Early initiation of end-of-life (EOL) conversations has been shown to improve patient agency in dying, increase early access to hospice care, and facilitate a dignified death. Despite the benefits of early initiation, EOL conversations do not occur as readily as physicians or patients wish. While medicine is commonly considered both a science and an art, increasing medicalization may narrow a clinician's focus towards procedures or specialized clinical frameworks rather than a patient's end-of-life wishes. Since physicians are ambassadors of clinical knowledge and are trusted patient advocates, it is important they facilitate EOL conversations early in the dying process. Patients desire …

Moving Toward, Moving Against, And Moving Away: An Interpersonal Approach To Construct Validation Of The Horney–Coolidge Type Inventory, Steven E. Carlson, Timothy W. Smith, Kimberly A. Parkhurst, Ruben Tinajero, Jeremy L. Grove, Christian Goans, Michiyo Hirai, John M. Ruiz

Psychological Science Faculty Publications

Karen Horney’s interpersonal theory of adjustment defined three different neurotic trends involving characteristic social behavior and motives: compliant (moving toward people), aggressive (moving against people), and detached (moving away from people). The Horney–Coolidge Type Inventory (HCTI) was developed to assess these trends, but has not been validated using standard methods in the interpersonal perspective. The studies reported here refined the structure of the HCTI, and utilized the structural summary method (SSM) to identify relationships of the three shortened HCTI trend scales with the interpersonal circumplex (IPC) in single university (n = 514) and multisite university (n = 3,283) …

Clinical And Demographic Differences By Sex In Autistic Venezuelan Children: A Cross-Sectional Study, Andy Torres, Cecilia Montiel-Nava

Psychological Science Faculty Publications

Background

Sex differences in symptom severity and adaptive function in children with ASD have been historically inconsistent and studies are predominantly from American- and European-residing populations. Alike, there is limited information on the complex interplay between sex, intelligence, adaptive function, and autism symptom severity; this is crucial to identify given their predictive value for health outcomes in autism

Aim

This study aimed to identify sex differences in autism symptom severity and adaptive function in a sample of Venezuelan children.

Method

One-hundred-and-three Venezuelan children ages 3–7 completed a comprehensive assessment for symptom severity, adaptive functioning, and intelligence.

Results

Sex differences were …

Integrated Pest And Pollinator Management, Ann Mull, Lori R. Spears, Marion Murray, Ricardo Ramirez

All Current Publications

An inextricable link exists between humans and pollinators, with benefits that include ecosystem health and function and human food security. Bees, butterflies, moths, wasps, flies, and beetles are responsible for most the world's pollination services. Considering the mounting scientific evidence denoting global pollinator declines, there is a critical need to prioritize pollinators and the essential services they provide. This fact sheet provides information about integrated pest and pollinator management (IPPM), which goes beyond integrated pest management (IPM) to include proactive, preventive measures that consider pollinators as well as pests in horticulture management.

Titan Success: Faculty Behind The Scenes, September, Thorpe Center

Publications from the Associate Deans

No abstract provided.

Novel Automation Of An Enzyme-Linked Immunosorbent Spot Assay Testing Method: Comparable Diagnostic Performance Of The T-Spot.Tb Test Using Manual Density Gradient Cell Isolation Versus Automated Positive Selection With The T-Cell Select Kit, Shu-Hua Wang, Murgesean V. S. Rajaram, Andre Trollip, Qian Wu, Doris Ayala, Danyelle Garza, Marielena A. Benavidez, Kelsie Fox, Genesis P. Aguillón-Durán, Blanca I. Restrepo

School of Medicine Publications

The diagnosis of latent tuberculosis (TB) infection (LTBI) is critical to improve TB treatment and control, and the T-SPOT.TB test is a commercial enzyme-linked immunosorbent spot assay used for this purpose. The objective of the study was to increase automation and extend the time between blood collection and processing for the T-SPOT.TB test from 0 to 8 h to 0 to 54 h. The previous maximum time between blood collection and processing for the T-SPOT.TB test is 32 h using T-Cell Xtend. For this, we compared the T-SPOT.TB test using manual peripheral blood mononuclear cell …

Why New Zealand’S Indigenous Reconciliation Process Has Failed To Empower Māori Fishers: Distributional, Procedural, And Recognition-Based Injustices, Hekia Bodwitch, Andrew M. Song, Owen Temby, John Reid, Megan Bailey, Gordon M. Hickey

School of Earth, Environmental, & Marine Sciences Faculty Publications

How is it that the New Zealand government’s process for re-establishing Indigenous fishing rights has failed to deliver thriving Māori fisheries? This paper examines why, at Te Waihora, a coastal lake, and site of one of the nation’s longest running and best-funded state-Māori co-governance agreements, Māori fishers have been unable to use their rights to support their fishery. As of 2018, the lake’s culturally and ecologically significant eel population was no longer commercially viable, a decline fishers have attributed to rampant dairy industry expansion upstream. Drawing on environmental justice literatures, we deploy a multi-dimensional framework to identify factors shaping possibilities …

Irrigation Decisions In Response To Groundwater Salinity In Kansas, Juhee Lee, Nathan P. Hendricks

School of Earth, Environmental, & Marine Sciences Faculty Publications

Understanding the interaction between groundwater salinity and irrigation decision making has important implications for groundwater management. Econometrics models were estimated using observed farmer behavior in response to different groundwater salinity levels in a region of Kansas. Estimation results demonstrate that farmers in the face of groundwater salinity change their irrigation decisions on irrigated acreage (i.e., extensive margin), crop choice (i.e., indirect intensive margin), and water application depth (i.e., direct intensive margin). The empirical results indicate an overall decrease in water use due to higher salinity, primarily through a decrease at the extensive margin.

Production Of Distilled Spirits Using Grain Sorghum Through Liquid Fermentation, Thomas Weiss, Jikai Zhao, Ruijia Hu, Meicen Liu, Yonghui Li, Yi Zheng, Gordon Smith, Donghai Wang

School of Earth, Environmental, & Marine Sciences Faculty Publications

The objectives of this research were to investigate the fermentation performance of US sorghum varieties for the production of distilled spirits as well as their associated coproducts and to study the formation of volatile compounds that are related to the flavor quality of the spirits. Three US sorghum varieties (red, white, and waxy sorghums) and four yeast strains (DADY, Ethanol Red, GR-2, and 71B) were used for distilled spirit production. Both sorghum variety and type of yeast strains had effects on alcohol concentration and alcohol yield. The alcohol concentration varied from 10.26 to 11.34% (v/v) while alcohol yield varied from …

Rh Blood Group D Antigen Genotyping Using A Portable Nanopore-Based Sequencing Device: Proof Of Principle, Wajnat A. Tounsi, Vasileios P. Lenis, Silja M. Tammi, Susanna Sainio, Katri Haimila, Neil D. Avent, Tracey E. Madgett

School of Biomedical Sciences

BACKGROUND: Nanopore sequencing is direct sequencing of a single-stranded DNA molecule using biological pores. A portable nanopore-based sequencing device from Oxford Nanopore Technologies (MinION) depends on driving a DNA molecule through nanopores embedded in a membrane using a voltage. Changes in current are then measured by a sensor, thousands of times per second and translated to nucleobases. METHODS: Genomic DNA (gDNA) samples (n = 13) were tested for Rh blood group D antigen (RHD) gene zygosity using droplet digital PCR. The RHD gene was amplified in 6 overlapping amplicons using long-range PCR. Amplicons were purified, and the sequencing library was …

Advanced Glycation End Products In Health And Disease, V. Prakash Reddy, Puspa Aryal, Emmanuel K. Darkwah

Chemistry Faculty Research & Creative Works

Advanced glycation end products (AGEs), formed through the nonenzymatic reaction of reducing sugars with the side-chain amino groups of lysine or arginine of proteins, followed by further glycoxidation reactions under oxidative stress conditions, are involved in the onset and exacerbation of a variety of diseases, including diabetes, atherosclerosis, and Alzheimer's disease (AD) as well as in the secondary stages of traumatic brain injury (TBI). AGEs, in the form of intra- and interprotein crosslinks, deactivate various enzymes, exacerbating disease progression. The interactions of AGEs with the receptors for the AGEs (RAGE) also result in further downstream inflammatory cascade events. The overexpression …

Polyphenols And Small Phenolic Acids As Cellular Metabolic Regulators, Mark Obrenovich, Yi Li, Moncef Tayahi, V. Prakash Reddy

Chemistry Faculty Research & Creative Works

Polyphenols and representative small phenolic acids and molecules derived from larger constituents are dietary antioxidants from fruits, vegetables and largely other plant-based sources that have ability to scavenge free radicals. What is often neglected in polyphenol metabolism is bioavailability and the role of the gut microbiota (GMB), which has an essential role in health and disease and participates in co-metabolism with the host. The composition of the gut microbiota is in constant flux and is modified by multiple intrinsic and extrinsic factors, including antibiotics. Dietary or other factors are key modulators of the host gut milieu. In this review, we …

Nitrogen And Iron Availability Drive Metabolic Remodeling And Natural Selection Of Diverse Phytoplankton During Experimental Upwelling, B. C. Kolody, S. R. Smith, L. Zeigler Allen, J. P. Mccrow, A. Moustafa, D. Shi, B. M. Hopkinson, F. M.M. Morel, B. B. Ward, A. E. Allen

Faculty Research, Scholarly, and Creative Activity

Nearly half of carbon fixation and primary production originates from marine phytoplankton, and much of it occurs in episodic blooms in upwelling regimes. Here, we simulated blooms limited by nitrogen and iron by incubating Monterey Bay surface waters with subnutricline waters and inorganic nutrients and measured the wholecommunity transcriptomic response during mid- and late-bloom conditions. Cell counts revealed that centric and pennate diatoms (largely Pseudo-nitzschia and Chaetoceros spp.) were the major blooming taxa, but dinoflagellates, prasinophytes, and prymnesiophytes also increased. Viral mRNA significantly increased in late bloom and likely played a role in the bloom's demise. We observed conserved shifts …

Pathways For Avian Influenza Virus Spread: Gps Reveals Wild Waterfowl In Commercial Livestock Facilities And Connectivity With The Natural Wetland Landscape, Fiona Mcduie, Elliott L. Matchett, Diann J. Prosser, John Y. Takekawa, Maurice E. Pitesky, Austen A. Lorenz, Madeline M. Mccuen, T. Overton Cory, Joshua T. Ackerman, Susan E.W. De La Cruz, Michael L. Casazza

Faculty Research, Scholarly, and Creative Activity

Zoonotic diseases are of considerable concern to the human population and viruses such as avian influenza (AIV) threaten food security, wildlife conservation and human health. Wild waterfowl and the natural wetlands they use are known AIV reservoirs, with birds capable of virus transmission to domestic poultry populations. While infection risk models have linked migration routes and AIV outbreaks, there is a limited understanding of wild waterfowl presence on commercial livestock facilities, and movement patterns linked to natural wetlands. We documented 11 wild waterfowl (three Anatidae species) in or near eight commercial livestock facilities in Washington and California with GPS telemetry …

Efficacy And Safety Of Ofatumumab In Recently Diagnosed, Treatment-Naive Patients With Multiple Sclerosis: Results From Asclepios I And Ii, Jutta Gärtner, Stephen L Hauser, Amit Bar-Or, Xavier Montalban, Jeffrey A Cohen, Anne H Cross, Kumaran Deiva, Habib Ganjgahi, Dieter A Häring, Bingbing Li, Ratnakar Pingili, Krishnan Ramanathan, Wendy Su, Roman Willi, Bernd Kieseier, Ludwig Kappos

2020-Current year OA Pubs

BACKGROUND: In the phase III ASCLEPIOS I and II trials, participants with relapsing multiple sclerosis receiving ofatumumab had significantly better clinical and magnetic resonance imaging (MRI) outcomes than those receiving teriflunomide.

OBJECTIVES: To assess the efficacy and safety of ofatumumab versus teriflunomide in recently diagnosed, treatment-naive (RDTN) participants from ASCLEPIOS.

METHODS: Participants were randomized to receive ofatumumab (20 mg subcutaneously every 4 weeks) or teriflunomide (14 mg orally once daily) for up to 30 months. Endpoints analysed post hoc in the protocol-defined RDTN population included annualized relapse rate (ARR), confirmed disability worsening (CDW), progression independent of relapse activity (PIRA) and …