Life Sciences Commons^™

Neuroscience, Criminal Sentencing, And Human Rights, Elizabeth Shaw

William & Mary Law Review

This Article discusses ways in which neuroscience should inform criminal sentencing in the future. Specifically, it compares the ethical permissibility of traditional forms of punishment, such as incarceration, on the one hand, and rehabilitative “neurointerventions” on the other. Rehabilitative neurointerventions are interventions that aim directly to modify brain activity in order to reduce reoffending. Various jurisdictions are already using techniques that could be classed as neurointerventions, and research suggests that, potentially, an even wider range of rehabilitative neurointerventions may be developed. This Article examines the role of human rights (in particular, the moral right to mental integrity and the legal …

Evaluation Of The Type I Error Rate When Using Parametric Bootstrap Analysis Of A Cluster Randomized Controlled Trial With Binary Outcomes And A Small Number Of Clusters, Lilian Golzarri-Arroyo, Stephanie L Dickinson, Yasaman Jamshidi-Naeini, Roger S Zoh, Andrew W Brown, Arthur H Owora, Peng Li, J Michael Oakes, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Cluster randomized controlled trials (cRCTs) are increasingly used but must be analyzed carefully. We conducted a simulation study to evaluate the validity of a parametric bootstrap (PB) approach with respect to the empirical type I error rate for a cRCT with binary outcomes and a small number of clusters.

Methods: We simulated a case study with a binary (0/1) outcome, four clusters, and 100 subjects per cluster. To compare the validity of the test with respect to error rate, we simulated the same experiment with K=10, 20, and 30 clusters, each with 2,000 simulated datasets. To test the null …

An Abductive Argument From Depression And Anxiety To Christian Personal Holiness, Kelly Douglas Burchett

Masters Theses

The science on pathological depression and anxiety (D&A) describes religion and spirituality's (R/S) insulating and immunizing effects in roughly 72 to 85 percent of all relevant articles. But the descriptivism of science cannot assign any normative value to a theological worldview. Deductive logic favors theism via Leibnizian contingency, Kalām cosmology, objective morality, fine-tuning of the universe, and abstract conceptualism. The information in DNA, the irreducible complexity of intracellular machinery, the improbability of folded proteins, and the support for common modular design over common ancestry establish a design inference for all of life. Unguided naturalistic simulations fail to surmount the complexity …

Measurable Microcystin In Ozark Streams Was Rare During Summer 2018 Baseflow Conditions, Bradley J. Austin, Brian E. Haggard

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Accelerated eutrophication due to human activity has been linked to an increase in the occurrence of cyanobacteria in freshwater systems. The purpose of this study was to document the occurrence of microcystin, a common cyanotoxin, within northwest Arkansas streams. Twenty streams were sampled from May through October 2018, and water and periphyton samples were analyzed for microcystin and chlorophyll-a (CHL-a). Mean microcystin concentrations in water samples were low across sites, ranging from < 0.10 to 0.21 μg L⁻¹. Mean microcystin in the periphyton across sites ranged from 2.6 to 9.9 μg m⁻² and were within values observed in the literature. …

Stock Cut Flower Production In Utah, Maegen Lewis, Melanie Stock, Brent Black, Dan Drost

All Current Publications

Stock (Matthiola incana) is a cool-season annual in Utah with the highest quality stems being produced in spring and fall. Plants produce a single stem with either single or double florets that are known for their sweet and strong clove-like scent. Stock can be transplanted in the high tunnel and field in early spring and is tolerant of light frosts. Stems require a trellis to promote straight growth and can reach 36 inches tall. In North Logan, UT, stock grown in a high tunnel began blooming 5-10 weeks earlier, had 55% greater marketability, and stems averaged 4-8 inches …

Measurable Microcystin In Ozark Streams Was Rare During Summer 2018 Baseflow Conditions, Bradley J. Austin, Brian E. Haggard

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Accelerated eutrophication due to human activity has been linked to an increase in the occurrence of cyanobacteria in freshwater systems. The purpose of this study was to document the occurrence of microcystin, a common cyanotoxin, within northwest Arkansas streams. Twenty streams were sampled from May through October 2018, and water and periphyton samples were analyzed for microcystin and chlorophyll-a (CHL-a). Mean microcystin concentrations in water samples were low across sites, ranging from < 0.10 to 0.21 μg L⁻¹. Mean microcystin in the periphyton across sites ranged from 2.6 to 9.9 μg m⁻² and were within values observed in the literature. …

High Resistance To Quinclorac In Multiple-Resistant Echinochloa Colona Associated With Elevated Stress Tolerance Gene Expression And Enriched Xenobiotic Detoxification Pathway, Gulab Rangani, Christopher E. Rouse, Christopher Saski, Rooksana E. Noorai, Vijay Shankar, Amy L. Lawton-Rauh, Isabel S. Werle, Nilda Roma-Burgos

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Echinochloa colona and other species in this genus are a threat to global rice production and food security. Quinclorac, an auxin mimic, is a common herbicide for grass weed control in rice, and Echinochloa spp. have evolved resistance to it. The complete mode of quinclorac action and subsequent evolution of resistance is not fully understood. We analyzed the de novo transcriptome of multiple-herbicide-resistant (ECO-R) and herbicide-susceptible genotypes in response to quinclorac. Several biological processes were constitutively upregulated in ECO-R, including carbon metabolism, photosynthesis, and ureide metabolism, indicating improved metabolic efficiency. The transcriptional change in ECO-R following quinclorac treatment indicates an …

Large-Scale Integrative Analysis Of Soybean Transcriptome Using An Unsupervised Autoencoder Model, Lingtao Su, Chunhui Xu, Shuai Zeng, Li Su, Trupti Joshi, Gary Stacey, Dong Xu

Biomedical Sciences

Plant tissues are distinguished by their gene expression patterns, which can help identify tissue-specific highly expressed genes and their differential functional modules. For this purpose, large-scale soybean transcriptome samples were collected and processed starting from raw sequencing reads in a uniform analysis pipeline. To address the gene expression heterogeneity in different tissues, we utilized an adversarial deconfounding autoencoder (AD-AE) model to map gene expressions into a latent space and adapted a standard unsupervised autoencoder (AE) model to help effectively extract meaningful biological signals from the noisy data. As a result, four groups of 1,743, 914, 2,107, and 1,451 genes were …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H. Rahbar, Nicole Y. Fatheree, Deborah A. Pearson, Rosleen Mansour, Melissa R. Van Arsdall, Fernando Navarro, J. Marc Rhoads

Department of Food Science and Technology: Faculty Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and …

Prognostic And Predictive Biomarkers In Patients With Coronavirus Disease 2019 Treated With Tocilizumab In A Randomized Controlled Trial, Jennifer Tom, Min Bao, Larry Tsai, Aditi Qamra, David Summers, Montserrat Carrasco-Triguero, Jacqueline Mcbride, Carrie M Rosenberger, Celia J F Lin, William Stubbings, Kevin G Blyth, Jordi Carratalà, Bruno François, Thomas Benfield, Derrick Haslem, Paolo Bonfanti, Cor H Van Der Leest, Nidhi Rohatgi, Lothar Wiese, Charles Edouard Luyt, Farrah Kheradmand, Ivan O Rosas, Fang Cai

Faculty, Staff and Students Publications

OBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumonia after treatment with tocilizumab, an anti-interleukin-6 receptor antibody, using data from the COVACTA trial in patients hospitalized with severe coronavirus disease 2019 pneumonia.

DESIGN: Exploratory analysis from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial.

SETTING: Hospitals in North America and Europe.

PATIENTS: Adults hospitalized with severe coronavirus disease 2019 pneumonia receiving standard care.

INTERVENTION: Randomly assigned 2:1 to IV tocilizumab 8 mg/kg or placebo.

MEASUREMENTS AND MAIN …

Evaluation Of Factors Underlying Sex-Based Disparities In Cardiovascular Care In Adults With Self-Reported Premature Atherosclerotic Cardiovascular Disease, Vardhmaan Jain, Mahmoud Al Rifai, Rodman Turpin, Hatice Nur Eken, Ankit Agrawal, Dhruv Mahtta, Zainab Samad, Stephanie Coulter, Fatima Rodriguez, Laura A Petersen, Salim S Virani

Faculty, Staff and Students Publications

IMPORTANCE: There are limited data regarding sex-based differences in physical and mental health domains and health care access in adults with premature atherosclerotic cardiovascular disease (ASCVD).

OBJECTIVE: To study the association of sex with physical and mental health domains as well as health care access-related factors among adults with self-reported premature ASCVD.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort analysis of 748 090 adults aged 18 to 55 years in the Behavioral Risk Factor Surveillance System 2016 to 2019 in the US. Data were analyzed from June to July 2021.

EXPOSURES: Self-reported ASCVD, defined as having a history of coronary artery …

Identifying Causative Microorganisms In Left Ventricular Assist Device Infections As A Guide For Developing Bacteriophage Therapy, Ishan Kamat, Harveen Lamba, Casey Hines-Munson, Samuel Hudson, Kenneth Liao, Kenneth L Muldrew, Sabrina Green, Austen Terwilliger, Heidi B Kaplan, Robert F Ramig, Anthony Maresso, Barbara W Trautner

Faculty, Staff and Students Publications

BACKGROUND: As more left ventricular-assist devices (LVADs) are implanted, multidrug-resistant LVAD infections are becoming increasingly common, partly due to bacterial biofilm production. To aid in developing bacteriophage therapy for LVAD infections, we have identified the most common bacterial pathogens that cause LVAD driveline infections (DLIs) in our heart transplant referral center.

MATERIALS AND METHODS: We studied a retrospective cohort of patients who received LVADs from November 2003 to August 2017 to identify the common causative organisms of LVAD infection. We also studied a prospective cohort of patients diagnosed with DLIs from October 2018 to May 2019 to collect bacterial strains …

Functional And Conformational Plasticity Of An Animal Group 1 Lea Protein, Brett Janis, Clinton Belott, Tyler Brockman, Michael Menze

Faculty and Staff Scholarship

Group 1 (Dur-19, PF00477, LEA_5) Late Embryogenesis Abundant (LEA) proteins are present in organisms from all three domains of life, Archaea, Bacteria, and Eukarya. Surprisingly, Artemia is the only genus known to include animals that express group 1 LEA proteins in their desiccation-tolerant life-history stages. Bioinformatics analysis of circular dichroism data indicates that the group 1 LEA protein AfLEA1 is surprisingly ordered in the hydrated state and undergoes during desiccation one of the most pronounced disorder-to-order transitions described for LEA proteins from A. franciscana. The secondary structure in the hydrated state is dominated by random coils (42%) and β-sheets (35%) …

Now You See Me: “First” Records Of The Greater Amberjack Seriola Dumerili At Rapa Nui Range Extension Or Increased Scientific Effort?, Naiti Morales, Amy Rose Coghlan, Erin E. Easton, Alan M. Friedlander, James J. Herlan, Carlos F. Gaymer

School of Earth, Environmental, & Marine Sciences Faculty Publications

We report new records of the fisheries-harvested subtropical greater amberjack Seriola dumerili for the south-east Pacific Ocean. Previously, only one species of Seriola (the yellowtail amberjack Seriola lalandi) was scientifically recorded for Rapa Nui (also known as Easter Island) despite local fishers' asserting that three Seriola morphotypes are found in the region. Here we present the first 'scientific record' of what could be a pre-existing (albeit transient) species of the Rapa Nui ecoregion. Establishing the existing range limits of commercially and ecologically valuable species is key for observing climate-driven distribution shifts, and the inclusion of traditional ecological knowledge is likely …

Comparative Evaluation Of Physicochemical And Fermentative Responses Of Three Sorghum Varieties From Dryland And Irrigated Land And The Properties Of Proteins From Distillers’ Grains, Jikai Zhao, Thomas Weiss, Zhenjiao Du, Shan Hong, Scott R. Bean, Yonghui Li, Donghai Wang

School of Earth, Environmental, & Marine Sciences Faculty Publications

Three sorghum varieties [waxy sorghum (WS), high protein sorghum (HPS), and normal sorghum (NS)] grown under dryland and irrigated conditions were evaluated with respect to the physicochemical and fermentative properties. The proteins were extracted from wet distillers' grains with solubles (WDGS) and characterized in terms of purity and in vitro digestibility. Starch, crude protein, crude fat, and fiber contents of the sorghums ranged from 64.16 to 68.05 g/100 g, 11.49–13.54 g/100 g, 2.45–2.98 g/100 g, and 1.62–1.80 g/100 g, respectively. For the same variety, the sorghums grown under dryland conditions had higher protein (0.33–0.91 g/100 g) and lower …

Effect Of Dicamba On Reproductive Development In Corn And Rice, Mason Castner, Jason K. Norsworthy, L. Tom Barber, Trenton Lee Roberts, Edward E. Gbur

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Research has been published regarding the effects of sublethal dicamba rates applied at different growth stages in soybean [Glycine max (L.) Merr.]; however, there is limited research on the effect of dicamba on reproductive growth in corn (Zea mays L.) and rice (Oryza sativa L.). Experiments were conducted in 2018 and 2019 to determine the potential consequences of dicamba exposure to reproductive stages of corn and rice. Dicamba was applied at 0.56, 5.6, 56, and 560 g ae ha^–1, with a 1X rate being 560 g ae ha^–1. Each rate was applied at …

Soil Organic Carbon And Nutrients Affected By Tree Species And Poultry Litter In A 17-Year Agroforestry Site, Helen C.S. Amorim, Amanda J. Ashworth, Yuri L. Zinn, Thomas J. Sauer

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Tree species and fertilization sources may affect the soil organic carbon (SOC) and fertility in agroforestry (AF) systems in temperate regions, but this remains unexplored. This study assesses the longitudinal trends in the SOC and major nutrients in a 17-year AF site established on an Ultisol in Fayetteville, AR. We evaluated how management and fertilization (mineral vs. organic) affect the soil’s physical and chemical properties using the tree species: red oak (Quercus rubra L.) and pecan Carya illinoinensis (Wangenh.) K. Koch. Long-term applications of poultry litter increased the soil pH, whereas the Mg and S concentrations decreased compared to …

Mytrials: Clinical Trial Application Concept, Katie Hollister

Graphic Communication

A clinical trial’s success is dependent upon whether a patient attends their highly-structured clinical trial visit schedule, which may include both in-person clinic visits and virtual check-in visits. MyTrials is a clinical trial journey app prototype that enables patients to schedule, reschedule, and attend join their in-person or virtual clinic visits. This product seeks to reduce the burden that scheduling places on the patient, and provides trial-provided resources and a daily and weekly timeline to help patients navigate their clinical trial journey.

School Breakfast And Student Behavior, Andres Cuadros-Menaca, Michael R. Thomsen, Rodolfo M. Nayga Jr.

Agricultural Economics and Agribusiness Faculty Publications and Presentations

The School Breakfast Program (SBP) is one of the largest nutrition assistance programs serving school-aged children in the US. It provides reimbursement to states for the operation of breakfast programs in schools. Student participation in the SBP is, however, much lower than the National School Lunch Program (NSLP). Because missing breakfast could result in hunger that could then influence children's interpersonal relations and classroom behavior (i.e., disciplinary infractions), some schools have implemented breakfast after the bell (BAB), which encompasses alternative breakfast delivery methods that make breakfast available to children after the school day commences. We use a difference-in-differences design with …

A Literary Examination Of The Efficacy Of Zoological Conservation In The United States Versus Foreign Efforts, Madeleine M. Lecorre

University Honors Theses

Falling into the top four threats to biodiversity, human activity is impacting species around the globe like never before. Zoological conservation of threatened species aids in the support and reestablishment of these dwindling populations. The examination of conservation work done in the U.S compared to foreign efforts provides insight into strengths, reveals weaknesses, and will help us better serve threatened species around the world. The status of conservation in the U.S. as well as foreign efforts were assessed through literary review of published reports from accredited organizations. As zoologic conservation aims to conserve threatened species, it is also important to …

Genetic Diversity Of Wild And Cultivated Muscadine Grapes (Vitis Rotundifolia Michx.), Kenneth Buck, Margaret Worthington

Horticulture Faculty Publications and Presentations

The muscadine (Vitis rotundifolia syn. Muscadinia rotundifolia) is an American grape species native to the southeastern United States that has been cultivated for centuries. Muscadines are one of three grape species in subgenus Muscadinia with a chromosome number of 2n = 40 (V. rotundifolia, Vitis munsoniana, and Vitis popenoei), making them genetically distinct from the European wine and table grape (Vitis vinifera) and other species in subgenus Euvitis. Crop improvement efforts have been continuous since the late 19th century, yet the germplasm that served as the foundation for early muscadine …

Perioperative Nivolumab Monotherapy Versus Nivolumab Plus Ipilimumab In Resectable Hepatocellular Carcinoma: A Randomised, Open-Label, Phase 2 Trial, Ahmed Omar Kaseb, Elshad Hasanov, Hop Sanderson Tran Cao, Lianchun Xiao, Jean-Nicolas Vauthey, Sunyoung S Lee, Betul Gok Yavuz, Yehia I Mohamed, Aliya Qayyum, Sonali Jindal, Fei Duan, Sreyashi Basu, Shalini S Yadav, Courtney Nicholas, Jing Jing Sun, Kanwal Pratap Singh Raghav, Asif Rashid, Kristen Carter, Yun Shin Chun, Ching-Wei David Tzeng, Divya Sakamuri, Li Xu, Ryan Sun, Vittorio Cristini, Laura Beretta, James C Yao, Robert A Wolff, James Patrick Allison, Padmanee Sharma

Faculty, Staff and Student Publications

BACKGROUND: Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma.

METHODS: In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 …

Naked (N) Mutant Mice Carry A Nonsense Mutation In The Homeobox Of Hoxc13, Carlos J Perez, Lars Mecklenburg, Almudena Fernandez, Marta Cantero, Tiago Antonio De Souza, Kevin Lin, Sharon Y R Dent, Lluis Montoliu, Alexander Awgulewitsch, Fernando Benavides

Faculty, Staff and Student Publications

Loss of function mutations in HOXC13 have been associated with Ectodermal Dysplasia-9, Hair/Nail Type (ECTD9) in consanguineous families, characterized by sparse to complete absence of hair and nail dystrophy. Here we characterize the spontaneous mouse mutation Naked (N) as a terminal truncation in the Hoxc13 (homeobox C13) gene. Similar to previous reports for homozygous Hoxc13 knock-out (KO) mice, homozygous N/N mice exhibit generalized alopecia with abnormal nails and a short lifespan. However, in contrast to Hoxc13 heterozygous KO mice, N/+ mice show generalized or partial alopecia, associated with loss of hair fibres, along with normal lifespan and fertility. Our data …

Interleukin-6 Blockade Abrogates Immunotherapy Toxicity And Promotes Tumor Immunity, Ahmed Omar Kaseb, Elshad Hasanov, Hop Sanderson Tran Cao, Lianchun Xiao, Jean-Nicolas Vauthey, Sunyoung S Lee, Betul Gok Yavuz, Yehia I Mohamed, Aliya Qayyum, Sonali Jindal, Fei Duan, Sreyashi Basu, Shalini S Yadav, Courtney Nicholas, Jing Jing Sun, Kanwal Pratap Singh Raghav, Asif Rashid, Kristen Carter, Yun Shin Chun, Ching-Wei David Tzeng, Divya Sakamuri, Li Xu, Ryan Sun, Vittorio Cristini, Laura Beretta, James C Yao, Robert A Wolff, James Patrick Allison, Padmanee Sharma

Faculty, Staff and Student Publications

BACKGROUND: Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma.

METHODS: In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 …

Methyl-Lysine Readers Phf20 And Phf20l1 Define Two Distinct Gene Expression-Regulating Nsl Complexes, Hieu T Van, Peter R Harkins, Avni Patel, Abhinav K Jain, Yue Lu, Mark T Bedford, Margarida A Santos

Faculty, Staff and Student Publications

The methyl-lysine readers plant homeodomain finger protein 20 (PHF20) and its homolog PHF20-like protein 1 (PHF20L1) are known components of the nonspecific lethal (NSL) complex that regulates gene expression through its histone acetyltransferase activity. In the current model, both PHF homologs coexist in the same NSL complex, although this was not formally tested; nor have the functions of PHF20 and PHF20L1 regarding NSL complex integrity and transcriptional regulation been investigated. Here, we perform an in-depth biochemical and functional characterization of PHF20 and PHF20L1 in the context of the NSL complex. Using mass spectrometry, genome-wide chromatin analysis, and protein-domain mapping, we …

Metabolic Stress Induces Gd2+ Cancer Stem Cell-Like Phenotype In Triple-Negative Breast Cancer, Appalaraju Jaggupilli, Stanley Ly, Khoa Nguyen, Vivek Anand, Bin Yuan, Fouad El-Dana, Yuanqing Yan, Zoe Arvanitis, Danthasinghe Waduge Badrajee Piyarathna, Nagireddy Putluri, Helen Piwnica-Worms, Henry Charles Manning, Michael Andreeff, V Lokesh Battula

Faculty, Staff and Student Publications

Background: Metabolic stress resulting from nutrient deficiency is one of the hallmarks of a growing tumour. Here, we tested the hypothesis that metabolic stress induces breast cancer stem-like cell (BCSC) phenotype in triple-negative breast cancer (TNBC).

Methods: Flow cytometry for GD2 expression, mass spectrometry and Ingenuity Pathway Analysis for metabolomics, bioinformatics, in vitro tumorigenesis and in vivo models were used.

Results: Serum/glucose deprivation not only increased stress markers but also enhanced GD2+ BCSC phenotype and function in TNBC cells. Global metabolomics profiling identified upregulation of glutathione biosynthesis in GD2high cells, suggesting a role of glutamine in the BCSC phenotype. Cueing …

Stem Cell Architecture Drives Myelodysplastic Syndrome Progression And Predicts Response To Venetoclax-Based Therapy, Irene Ganan-Gomez, Hui Yang, Feiyang Ma, Guillermo Montalban-Bravo, Natthakan Thongon, Valentina Marchica, Guillaume Richard-Carpentier, Kelly Chien, Ganiraju Manyam, Feng Wang, Ana Alfonso, Shuaitong Chen, Caleb Class, Rashmi Kanagal-Shamanna, Justin P Ingram, Yamini Ogoti, Ashley Rose, Sanam Loghavi, Pamela Lockyer, Benedetta Cambo, Muharrem Muftuoglu, Sarah Schneider, Vera Adema, Michael Mclellan, John Garza, Matteo Marchesini, Nicola Giuliani, Matteo Pellegrini, Jing Wang, Jason Walker, Ziyi Li, Koichi Takahashi, Joel D Leverson, Carlos Bueso-Ramos, Michael Andreeff, Karen Clise-Dwyer, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cells (HSCs). The current standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, almost 50% of MDS patients fail HMA therapy and progress to acute myeloid leukemia, facing a dismal prognosis due to lack of approved second-line treatment options. As cancer stem cells are the seeds of disease progression, we investigated the biological properties of the MDS HSCs that drive disease evolution, seeking to uncover vulnerabilities that could be therapeutically exploited. Through integrative molecular profiling of HSCs and progenitor cells in large patient cohorts, we found …

Subtype-Specific And Co-Occurring Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Saber Tadros, Alyssa Bouska, Tayla Heavican, Haopeng Yang, Qing Deng, Dalia Moore, Ariz Akhter, Keenan Hartert, Neeraj Jain, Jordan Showell, Sreejoyee Ghosh, Lesley Street, Marta Davidson, Christopher Carey, Joshua Tobin, Deepak Perumal, Julie M Vose, Matthew A Lunning, Aliyah R Sohani, Benjamin J Chen, Shannon Buckley, Loretta J Nastoupil, R Eric Davis, Jason R Westin, Nathan H Fowler, Samir Parekh, Maher Gandhi, Sattva Neelapu, Douglas Stewart, Kapil Bhalla, Javeed Iqbal, Timothy Greiner, Scott J Rodig, Adnan Mansoor, Michael R Green

Faculty, Staff and Student Publications

B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, …

Inhibition Of Calcium-Triggered Secretion By Hydrocarbon-Stapled Peptides, Ying Lai, Giorgio Fois, Jose R Flores, Michael J Tuvim, Qiangjun Zhou, Kailu Yang, Jeremy Leitz, John Peters, Yunxiang Zhang, Richard A Pfuetzner, Luis Esquivies, Philip Jones, Manfred Frick, Burton F Dickey, Axel T Brunger

Faculty, Staff and Student Publications

Membrane fusion triggered by Ca2+ is orchestrated by a conserved set of proteins to mediate synaptic neurotransmitter release, mucin secretion and other regulated exocytic processes1-4. For neurotransmitter release, the Ca2+ sensitivity is introduced by interactions between the Ca2+ sensor synaptotagmin and the SNARE complex5, and sequence conservation and functional studies suggest that this mechanism is also conserved for mucin secretion6. Disruption of Ca2+-triggered membrane fusion by a pharmacological agent would have therapeutic value for mucus hypersecretion as it is the major cause of airway obstruction in the pathophysiology of respiratory viral infection, asthma, chronic obstructive pulmonary disease and cystic fibrosis7-11. …

Targeting Mitochondrial Respiration And The Bcl2 Family In High-Grade Myc-Associated B-Cell Lymphoma, Giulio Donati, Micol Ravà, Marco Filipuzzi, Paola Nicoli, Laura Cassina, Alessandro Verrecchia, Mirko Doni, Simona Rodighiero, Federica Parodi, Alessandra Boletta, Christopher P Vellano, Joseph R Marszalek, Giulio F Draetta, Bruno Amati

Faculty, Staff and Student Publications

Multiple molecular features, such as activation of specific oncogenes (e.g., MYC, BCL2) or a variety of gene expression signatures, have been associated with disease course in diffuse large B-cell lymphoma (DLBCL), although their relationships and implications for targeted therapy remain to be fully unraveled. We report that MYC activity is closely correlated with-and most likely a driver of-gene signatures related to oxidative phosphorylation (OxPhos) in DLBCL, pointing to OxPhos enzymes, in particular mitochondrial electron transport chain (ETC) complexes, as possible therapeutic targets in high-grade MYC-associated lymphomas. In our experiments, indeed, MYC sensitized B cells to the ETC complex I inhibitor …