Digital Commons Network^™

Targeting Snai1-Mediated Colorectal Cancer Chemoresistance And Stemness By Sphingosine Kinase 2 Inhibition, Harinarayanan Janakiraman, Zachary Gao, Yun Zhu, Jiangling Dong, Scott A Becker, Alhaji Janneh, Besim Ogretmen, E Ramsay Camp

Faculty, Staff and Students Publications

BACKGROUND: Epithelial-to-mesenchymal transition (EMT), cancer stem cells (CSCs), and colorectal cancer (CRC) therapy resistance are closely associated. Prior reports have demonstrated that sphingosine-1-phosphate (S1P) supports stem cells and maintains the CSC phenotype. We hypothesized that the EMT inducer SNAI1 drives S1P signaling to amplify CSC self-renewal capacity and chemoresistance.

METHODS: CRC cell lines with or without ectopic expression of SNAI1 were used to study the role of S1P signaling as mediators of cancer stemness and 5-fluorouracil (5FU) chemoresistance. The therapeutic ability of sphingosine kinase 2 (SPHK2) was assessed using siRNA and ABC294640, a SPHK2 inhibitor. CSCs were isolated from patient-derived …

Psychological Distress Among Ethnically Diverse Participants From Eastern And Southern Africa, Kester B B Tindi, Allan Kalungi, Eugene Kinyanda, Bizu Gelaye, Alicia R Martin, Ronald Galiwango, Wilber Ssembajjwe, Fred Kirumira, Adele Pretorius, Anne Stevenson, Charles R J C Newton, Dan J Stein, Elizabeth G Atkinson, Emanuel K Mwesiga, Joseph Kyebuzibwa, Lori B Chibnik, Lukoye Atwoli, Mark Baker, Melkam Alemayehu, Rehema M Mwende, Rocky E Stroud, Solomon Teferra, Stella Gichuru, Symon M Kariuki, Zukiswa Zingela, Moffat Nyirenda, Segun Fatumo, Dickens H Akena

Faculty, Staff and Students Publications

IMPORTANCE: Psychological distress is characterized by anxiety and depressive symptoms. Although prior research has investigated the occurrence and factors associated with psychological distress in low- and middle-income countries, including those in Africa, these studies' findings are not very generalizable and have focused on different kinds of population groups.

OBJECTIVE: To investigate the prevalence and characteristics (sociodemographic, psychosocial, and clinical) associated with psychological distress among African participants.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study analyzed data of participants in the Neuropsychiatric Genetics in African Populations-Psychosis (NeuroGAP-Psychosis) study, which recruited from general outpatient clinics in Eastern (Uganda, Kenya, and Ethiopia) and Southern …

Decoding Complex Inherited Phenotypes In Rare Disorders: The Decipherd Initiative For Rare Undiagnosed Diseases In Chile, M Cecilia Poli, Boris Rebolledo-Jaramillo, Catalina Lagos, Joan Orellana, Gabriela Moreno, Luz M Martín, Gonzalo Encina, Daniela Böhme, Víctor Faundes, M Jesús Zavala, Trinidad Hasbún, Sara Fischer, Florencia Brito, Diego Araya, Manuel Lira, Javiera De La Cruz, Camila Astudillo, Guillermo Lay-Son, Carolina Cares, Mariana Aracena, Esteban San Martin, Zeynep Coban-Akdemir, Jennifer E Posey, James R Lupski, Gabriela M Repetto

Faculty, Staff and Students Publications

Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the "diagnostic odyssey" for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international …

Integrated Safety And Efficacy Analyses Of Phase 3 Trials Of A Microbiome Therapeutic For Recurrent Cdi, Colleen S Kraft, Matthew Sims, Michael Silverman, Thomas J Louie, Paul Feuerstadt, Edward S Huang, Sahil Khanna, Charles S Berenson, Elaine E L Wang, Stuart H Cohen, Louis Korman, Christine Lee, Colleen R Kelly, Alberto Odio, Paul P Cook, Bret Lashner, Mayur Ramesh, Princy Kumar, Ananya De, Asli Memisoglu, David A Lombardi, Brooke R Hasson, Barbara H Mcgovern, Lisa Von Moltke, Darrell S Pardi, Ecospor Iii And Ecospor Iv Investigators

Faculty, Staff and Students Publications

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI.

OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities.

METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest …

Circulating Blood Plasma Profiling Reveals Proteomic Signature And A Causal Role For Svep1 In Sudden Cardiac Death, Thuyvy Duong, Thomas R Austin, Jennifer A Brody, Ali Shojaie, Alexis Battle, Joel S Bader, Yun Soo Hong, Christie M Ballantyne, Josef Coresh, Robert E Gerszten, Russell P Tracy, Bruce M Psaty, Nona Sotoodehnia, Dan E Arking

Faculty, Staff and Students Publications

No abstract provided.

Horizontal Gene Transfer And Beyond: The Delivery Of Biological Matter By Bacterial Membrane Vesicles To Host And Bacterial Cells, Alice X Wen, Christophe Herman

Faculty, Staff and Students Publications

Membrane vesicles (MVs) are produced in all domains of life. In eukaryotes, extracellular vesicles have been shown to mediate the horizontal transfer of biological material between cells [1]. Therefore, bacterial MVs are also thought to mediate horizontal material transfer to host cells and other bacteria, especially in the context of cell stress. In this review, we discuss the mechanisms of bacterial MV production, evidence that their contents can be trafficked to host cells and other bacteria, and the biological relevance of horizontal material transfer by bacterial MVs.

Mutant Npm1 Marginally Impacts Ribosome Footprint In Acute Myeloid Leukemia Cells, Lorenzo Brunetti, Giulia Pianigiani, Michael C Gundry, Margaret A Goodell, Brunangelo Falini

Faculty, Staff and Students Publications

BACKGROUND:NPM1‐mutated acute myeloid leukemia (AML) is the most frequent AML subtype. As wild‐type NPM1 is known to orchestrate ribosome biogenesis, it has been hypothesized that altered translation may contribute to leukemogenesis and leukemia maintenance in NPM1‐mutated AML. However, this hypothesis has never been investigated. We reasoned that if mutant NPM1 (NPM1c) directly impacts translation in leukemic cells, loss of NPM1c would result in acute changes in the ribosome footprint.

METHODS: Here, we performed ribosome footprint profiling (Ribo-seq) and bulk messenger RNA (mRNA) sequencing in two

RESULTS AND DISCUSSION: Incubation of degron cells with the small compound dTAG-13 …

Design And Cohort Characteristics Of Track, A Prospective Study Of Hyperkalaemia Management Decision-Making, Judith Hsia, Nitin Shivappa, Ameet Bakhai, Jordi Bover, Javed Butler, Pietro Manuel Ferraro, Linda Fried, Markus P Schneider, Navdeep Tangri, Wolfgang C Winkelmayer, Meredith Bishop, Hungta Chen, Anna-Karin Sundin, Marc P Bonaca

Faculty, Staff and Students Publications

BACKGROUND: Guideline-recommended hyperkalaemia management includes dietary potassium (K

METHODS: This study enrolled participants within 21 days of an episode of hyperkalaemia in four European countries (UK, Spain, Germany, Italy) and the USA. During the 12-month follow up, data collected will include participant and healthcare provider characteristics (specialty and practice setting), hyperkalaemia treatment objectives and strategies, rationale for management decisions and indicators of response and patient-reported perceptions of their hyperkalaemia treatment.

RESULTS: The enrolled cohort includes 1330 participants, mean age 68 years, of whom 31% were women. At baseline, 6% reported heart failure, 55% chronic kidney disease, 29% both and 9% …

Metabolic Dependencies Of Acute Myeloid Leukemia Stem Cells, Xiangguo Shi, Mengdie Feng, Daisuke Nakada

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy primarily driven by an immature population of AML cells termed leukemia stem cells (LSCs) that are implicated in AML development, chemoresistance, and relapse. An emerging area of research in AML focuses on identifying and targeting the aberrant metabolism in LSCs. Dysregulated metabolism is involved in sustaining functional properties of LSCs, impeding myeloid differentiation, and evading programmed cell death, both in the process of leukemogenesis and in response to chemotherapy. This review discusses recent discoveries regarding the aberrant metabolic processes of AML LSCs that have begun to change the therapeutic landscape of …

Multicohort Epigenome-Wide Association Study Of All-Cause Cardiovascular Disease And Cancer Incidence: A Cardio-Oncology Approach, Arce Domingo-Relloso, Angela L Riffo-Campos, Naisi Zhao, Guillermo Ayala, Karin Haack, Carlos Manterola, Dorothy A Rhoades, Jason G Umans, M Daniele Fallin, Miguel Herreros-Martinez, Marina Pollan, Eric Boerwinkle, Elizabeth A Platz, Miranda R Jones, Jan Bressler, Roby Joehanes, Calen P Ryan, Juan R Gonzalez, Daniel Levy, Daniel W Belsky, Shelley A Cole, Dominique S Michaud, Ana Navas-Acien, Maria Tellez-Plaza

Faculty, Staff and Student Publications

BACKGROUND: Emerging evidence reveals a complex relationship between cardiovascular disease (CVD) and cancer, which share common risk factors and biological pathways.

OBJECTIVES: The aim of this study was to evaluate common epigenetic signatures for CVD and cancer incidence in 3 ethnically diverse cohorts: Native Americans from the SHS (Strong Heart Study), European Americans from the FHS (Framingham Heart Study), and European Americans and African Americans from the ARIC (Atherosclerosis Risk In Communities) study.

METHODS: A 2-stage strategy was used that included first conducting untargeted epigenome-wide association studies for each cohort and then running targeted models in the union set of …

Dna Methylation-Derived Immune Cell Proportions And Cancer Risk In Black Participants, Christopher S Semancik, Naisi Zhao, Devin C Koestler, Eric Boerwinkle, Jan Bressler, Rachel J Buchsbaum, Karl T Kelsey, Elizabeth A Platz, Dominique S Michaud

Faculty, Staff and Student Publications

Prior cohort studies assessing cancer risk based on immune cell subtype profiles have predominantly focused on White populations. This limitation obscures vital insights into how cancer risk varies across race. Immune cell subtype proportions were estimated using deconvolution based on leukocyte DNA methylation markers from blood samples collected at baseline on participants without cancer in the Atherosclerosis Risk in Communities Study. During a mean of 17.5 years of follow-up, 668 incident cancers were diagnosed in 2,467 Black participants. Cox proportional hazards regression was used to examine immune cell subtype proportions and overall cancer incidence and site-specific incidence (lung, breast, and …

Contemporary Epidemiology Of Hepatocellular Carcinoma: Understanding Risk Factors And Surveillance Strategies, Fouad Jaber, George Cholankeril, Hashem B El-Serag

Faculty, Staff and Students Publications

The contemporary epidemiology of hepatocellular carcinoma (HCC) shows a shift in the main etiological risk factors from less common but highly virulent (eg, hepatitis C and B) to more common but weak risk factors (eg, alcohol and metabolic syndrome). Therefore, we are in a seemingly paradoxical state of declining overall incidence rates of HCC-related to improved prevention and treatment of viral hepatitis but burgeoning number of people at an elevated risk of HCC. Several geographic regions have reported an increase in HCC attributable to alcoholic liver disease and metabolic dysfunction associated with steatotic liver disease (MASLD). The importance of risk …

Return To Eden: God’S Design For Human Sexuality In The Song Of Songs, Richard M. Davidson

Faculty Publications

No abstract provided.

Healthy From The Start: Co-Designing Sleep, Nutrition And Physical Activity Resources For Young Shiftworkers—Novel Implementation And Evaluation, Alexandra E. Shriane, Sally A. Ferguson, Gabrielle Rigney, Charlotte C. Gupta, Tracy Kolbe-Alexander, Madeline Sprajcer, Cassie Hilditch, Robert Stanton, Matthew J.W. Thomas, Jessica L. Paterson, Jamie Marino, Grace E. Vincent

Faculty Research, Scholarly, and Creative Activity

Introduction: The increasing prevalence of shiftwork among young adults poses significant health risks, primarily due to its disruptive effects on sleep, nutrition and physical activity. Addressing these risks necessitates the development of tailored, evidence-based resources to support these key health behaviours. Participatory research approaches, engaging those with relevant lived experience (i.e., co-design) are a novel and effective approach in developing these resources. As such, the aim of the present study was to explore whether sleep, nutrition and physical activity resources for young shiftworkers could be developed using participatory, co-design approaches and how co-designers would rate both the approaches used and …

Structural Basis For Adhesin Secretion By The Outer-Membrane Usher In Type 1 Pili, Ryan M Bitter, Maxwell I Zimmerman, Brock T Summers, Jerome S Pinkner, Karen W Dodson, Scott J Hultgren, Peng Yuan

2020-Current year OA Pubs

Gram-negative bacteria produce chaperone-usher pathway pili, which are extracellular protein fibers tipped with an adhesive protein that binds to a receptor with stereochemical specificity to determine host and tissue tropism. The outer-membrane usher protein, together with a periplasmic chaperone, assembles thousands of pilin subunits into a highly ordered pilus fiber. The tip adhesin in complex with its cognate chaperone activates the usher to allow extrusion across the outer membrane. The structural requirements to translocate the adhesin through the usher pore from the periplasm to the extracellular space remains incompletely understood. Here, we present a cryoelectron microscopy structure of a quaternary …

A Quadriocellar Hedychridium Caeruleum (Hymenoptera: Chrysididae) From Manitoba, Canada, Kira Peters, Jason Gibbs

The Great Lakes Entomologist

A specimen of Hedychridium caeruleum (Norton) with four ocelli was discovered in Manitoba, Canada. The supernumerary ocellus is located to the right of the ocellar triangle, which otherwise appears normal. This is the first report of an ocellar or ocular teratology within Chrysididae, adding to the small body of literature currently available on supernumerary ocelli within Hymenoptera. This is the first published record of H. caeruleum in Canada.

New Records Of Two Adventive Bee Species In Indiana (Hymenoptera: Colletidae; Megachilidae), Hannah G. Kernen, Robert P. Jean, Brock A. Harpur, Jacob Buck, Jennifer Noseworthy

The Great Lakes Entomologist

Here we report the first records of Pseudoanthidium nanum (Mocsáry) (Hymenoptera: Megachilidae) and Hylaeus hyalinatus Smith (Hymenoptera: Colletidae) for the state of Indiana. P. nanum was first detected in Gary, Lake County during August, 2023, and multiple specimens of H. hyalinatus were collected from 2021 to 2023 in Marion, Grant County. These records fill gaps in the Midwestern ranges of both species.

Confirmation Of Avian Dispersal Of A Seed Chalcid Wasp In North America And A New Host Record For Megastigmus Aculeatus (Hymenoptera: Megastigmidae), Julie A. Craves

The Great Lakes Entomologist

Dispersal of chalcid wasp larvae inhabiting the seeds of angiosperms by wild birds in North America has never been verified. I describe adult Megastigmus aculeatus Swederus that successfully emerged from seeds extracted from the droppings of six species of native North American non-captive birds. Rosa setigera is also confirmed as a host for this wasp for the first time.

Laboratory Rearing Methods For The Soybean Tentiform Leafminer (Lepidoptera: Gracillariidae), A New Pest Of Soybean, James Menger, Arthur Ribeiro, Fabio Fuhr, Robert L. Koch

The Great Lakes Entomologist

Soybean tentiform leafminer (STL), Macrosaccus morrisella (Fitch) (Lepidoptera: Gracillariidae), is a leaf-mining microlepidopteran native to North America that was recently discovered feeding on soybean, Glycine max (L.) Merr., in Canada and the United States. A laboratory rearing system for STL was developed on live soybean plants. The methods for continuous rearing or cyclic (i.e., generational) production of insects are described herein. All rearing was performed in a walk-in environmental chamber at 25°C (±2°C), with ~70% relative humidity and a photoperiod of 16:8 (L:D). Adults of STL were allowed to oviposit on clean soybean plants in an oviposition cage. Soybean plants …

Ambrosia Beetle (Coleoptera: Curculionidae: Scolytinae) Responses To Ice Storm Damage In Mesic, Mixed Deciduous Forests In Southeast Ohio, United States, Christopher J. Hayes, Richard M. Turcotte

The Great Lakes Entomologist

In the eastern United States abiotic forest disturbances are common and cause extensive tree damage. Freshly broken trees and tree branches attract bark and ambrosia beetles that utilize inner bark and xylem of damaged branches and trees to fill requisite habitat needs. An ice storm in February 2003 on the Wayne National Forest presented an opportunity to study the local ambrosia beetle species and their reaction to this storm event. Ethanol baited Lindgren traps were deployed from 2003-2006 starting in the summer after the storm. Eight native and introduced Scolytinae ambrosia beetle species were trapped in large numbers (>500 …

Impact Of Debarking And Bark Grinding On Survival Of Ips Calligraphus (Coleoptera: Curculionidae: Scolytinae), Robert A. Haack, Toby Petrice, John Foltz, Hui Ye

The Great Lakes Entomologist

Chipping and debarking of infested woody material such as branches and logs are common sanitation methods used to kill bark- and wood-infesting insects. The sixspined ips, Ips calligraphus (Germar), is a native North American bark beetle (Coleoptera: Curculionidae: Scolytinae) that infests several pine (Pinus) species. We evaluated I. calligraphus mortality after debarking and grinding, using 12 recently cut longleaf pine (Pinus palustris Mill.) logs that had undergone natural colonization for three weeks in Florida. Initial bark beetle densities were estimated from samples collected the day before debarking. Similar amounts of bark were collected at three steps in …

Phenology And Host Choice Among Common Yet Little Understood Wood Borers (Coleoptera: Bostrichidae) In A Midwestern Savanna, Noah I. Finney, Derek W. Rosenberger

The Great Lakes Entomologist

Horned powder-post beetles (Coleoptera: Bostrichidae) are a geographically widespread family of wood-boring beetles. While members of this family represent important grain pests, are often intercepted in ports, and may play an important role in ecosystem processes, little work has investigated bostrichid life history in their native ranges. This gap limits our ability to assess ecosystem services and invasiveness. Three native species, Amphicerus bicaudatus (Say), Scobicia bidentata (Horn), and Xylobiops basilaris (Say), are commonly found in savannas in Northern Illinois. Although little is currently known about the life history of S. bidentata, A. bicaudatus and X. basilaris can be minor pests …

Changes In Ground Beetle (Coleoptera: Carabidae) Species Assemblages After Removal Of Red Pine (Pinus Resinosa) Overstory On Dry Sand Prairie Sites In Michigan, Robert A. Haack, Toby Petrice, Robert L. Davidson, Robert E. Acciavatti

The Great Lakes Entomologist

Ground beetle (Coleoptera: Carabidae) species assemblages were studied at sites on the Huron-Manistee National Forests in Newaygo County, Michigan. The goal was to monitor changes in carabid diversity on areas where mature red pine (Pinus resinosa Sol. ex Aiton) was removed during the 1996-1997 winter and compare with carabid diversity at nearby natural dry sand prairie sites, natural oak-pine barrens, and uncut red pine stands. The red pine had been planted on dry sand prairie sites during 1940-1950. Sampling with pitfall traps occurred during May-August in both 1996 and 1997, but only July-August in 1999. Overall, 16,259 carabid specimens …

Tgle Vol. 57 Nos. 1 & 2 Cover Pages

The Great Lakes Entomologist

TGLE Vol. 57 Nos. 1 & 2 Cover Pages

Effectiveness Of A Fast- Vs. Slow-Velocity Training On Load-Velocity Characteristics In Older Adults: A Pilot Study, Blake Murphy, Kelley Hammond, Leland Barker, Mae Grahek, Mikayla Grocki, Jake A. Siedlik, Mitchel Magrini

International Journal of Exercise Science

Resistance training at fast velocities is suggested to be more effective for improving muscular strength and movement speed compared slow, heavy training. This study aimed to examine the effects of a fast-velocity (FVRT) compared to a slow-velocity (SVRT) resistance training program on maximal strength, maximal movement speed, and load-velocity characteristics in older adults. Nineteen community-dwelling older adults were randomly assigned to either the FVRT or SVRT group and completed a twice weekly, progressive resistance training protocol for 8-weeks. Both groups were instructed to move the weight “as fast as possible” and received movement velocity biofeedback. Absolute (1RM_ABS) and …

Diagnostic Overshadowing: A Delayed Diagnosis Of Autism Spectrum Disorder In A Deaf Child, Quynh-Chi Dang, Michael Hoffman, Rachel St. John

Journal of Early Hearing Detection and Intervention

Diagnostic overshadowing occurs when a patient with a pre-existing diagnosis presents with symptoms that are attributed to the diagnosis, but actually reflect a separate issue. This diagnostic overshadowing can lead to delays in diagnosis, as well as disparities in health care and outcomes. The following case will provide an example in which diagnostic overshadowing contributed to the delay of an autism diagnosis in a child who is deaf. With at least 40 to 50% of children who are deaf or hard of hearing having at least one co-existing medical/developmental condition, and the current prevalence of autism at 1 in 36 …

Utopian Genderscapes, Michelle C. Smith

Rhetoric

No abstract provided.

Intrinsic And Environmental Drivers Of Pairwise Cohesion In Wild Canis Social Groups, John F. Benson

School of Natural Resources: Faculty Publications

Animals within social groups respond to costs and benefits of sociality by adjusting the proportion of time they spend in close proximity to other individuals in the group (cohesion). Variation in cohesion between individuals, in turn, shapes important group-level processes such as subgroup formation and fission–fusion dynamics. Although critical to animal sociality, a comprehensive understanding of the factors influencing cohesion remains a gap in our knowledge of cooperative behavior in animals. We tracked 574 individuals from six species within the genus Canis in 15 countries on four continents with GPS telemetry to estimate the time that pairs of individuals within …

Dynamic Localization Of Endoplasmic Reticulum During Tetrahymena Conjugation, Guerrier Sabrice, Michael Patterson, Kaitlin Crofton, Michael Tucker, Shyhiem Walker

Faculty Publications

Changes in lipid composition at membrane fusion sites in mating Tetrahymena are thought to involve the endoplasmic reticulum (ER), but its localization to these sites has not been observed. Here we show ER distribution during Tetrahymena mating using TtRET1-GFP and GFP-KDEL. We find that both markers localize to perinuclear membranes and tubular structures that connect perinuclear membrane to plasma membrane at fusion sites. Interestingly, both markers disappear from parental macronuclei after emergence of zygotic macronuclei. These similarities in localization of established ER marker, GFP-KDEL, and TtRET1-GFP reveal TtRET1-GFP as a useful new live cell marker for the ER in Tetrahymena.

Adapting Or Resisting: The Resonance Of Pancasila’S Values Among Indonesian Students In Malaysia, Andy Dermawan, Haekal Adha Al-Giffari, Vita Fitria

Jurnal Civics: Media Kajian Kewarganegaraan

Pancasila, the foundational philosophy of Indonesia, serves as a unifying force in a diverse nation characterized by myriad islands, ethnicities, races, and religions. In a world where globalization and migration are prevalent, understanding how national values are maintained by citizens living abroad becomes increasingly significant. This study focuses on Indonesian students at the International Islamic University Malaysia (IIUM), a group representing a microcosm of the Indonesian diaspora. It explores how these students nurture and strengthen their nationalism and internalize Pancasila values despite residing in a foreign country. Utilizing qualitative research methods, with semi-structured interviews as a primary approach to dive …