Medicine and Health Sciences Commons^™

Vdac2 And Bak Scarcity In Liver Mitochondria Enables Targeting Hepatocarcinoma While Sparing Hepatocytes, Shamim Naghdi, Piyush Mishra, Soumya S. Roy, David Weaver, Ludivine Walter, Erika Davies, Anil N. Antony, Xuena Lin, Gisela Moehren, Mark A. Feitelson, Christopher A. Reed, Tullia Lindsten, Craig B. Thompson, Hien T. Dang, Jan B. Hoek, Erik S. Knudsen, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity. Exploring potential therapeutic targeting, we find that combinations of activators of the tBid pathway with inhibitors of the Bcl-2 family proteins …

Hematopoietic Cell Transplant Compared With Standard Care In Adolescents And Young Adults With Sickle Cell Disease, Mark C Walters, Mary Eapen, Yiwen Liu, Fuad El Rassi, Edmund K Waller, John E Levine, John J Strouse, Joseph H Antin, Suhag H Parikh, Nitya Bakshi, Carlton Dampier, Jennifer J Jaroscak, Shayla Bergmann, Trisha Wong, Vamsi Kota, Betty Pace, Lazaros J Lekakis, Premal Lulla, Robert S Nickel, Kimberly A Kasow, Uday Popat, Wally Smith, Lolie Yu, Nancy Difronzo, Nancy Geller, Naynesh Kamani, Elizabeth S Klings, Kathryn Hassell, Adam Mendizabal, Keith Sullivan, Donna Neuberg, Lakshmanan Krishnamurti

Faculty, Staff and Students Publications

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2 years after biologic assignment to a donor or no donor (SOC) arm based on the availability of an HLA-matched sibling or unrelated donor (BMT CTN 1503). A donor search was commenced after eligibility confirmation. The primary end point was a comparison of survival between the treatment arms 2 years after biologic assignment. Power calculations required 60 participants in the donor arm and 140 in the no donor arm to determine if early transplant-related mortality …

Navigating The Landscape Of Reinterventions After Tavr, Gilbert H L Tang, Syed Zaid, Ole De Backer

Faculty, Staff and Students Publications

No abstract provided.

Longitudinal Multi-Omics In Alpha-Synuclein Drosophila Model Discriminates Disease- From Age-Associated Pathologies In Parkinson’S Disease, Justin Moore, Timothy Wu, Justin Dhindsa, Omar El Fadel, Anh Le, Alma Perez, Bismark Amoh, Akash Tarkunde, Katy F Zhu, Matthew Avalos, Eric B Dammer, Duc M Duong, Nicholas T Seyfried, Joshua M Shulman, Ismael Al-Ramahi, Juan Botas

Duncan NRI Faculty and Staff Publications

Parkinson's disease (PD) starts decades before symptoms appear, usually in the later decades of life, when age-related changes are occurring. To identify molecular changes early in the disease course and distinguish PD pathologies from aging, we generated Drosophila expressing alpha-synuclein (αSyn) in neurons and performed longitudinal bulk transcriptomics and proteomics on brains at six time points across the lifespan and compared the data to healthy control flies as well as human post-mortem brain datasets. We found that translational and energy metabolism pathways were downregulated in αSyn flies at the earliest timepoints; comparison with the aged control flies suggests that elevated …

Metabolic Signatures In Adipose Tissue Linking Lipophilic Persistent Organic Pollutant Mixtures To Blood Pressure Five Years After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Douglas I Walker, Brittney O Baumert, Hongxu Wang, Jesse A Goodrich, Sarah Rock, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Scott M Bartell, Stavra Xanthakos, Xiangping Lin, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Michele A La Merill, Erika Garcia, Max T Aung, Sandrah P Eckel, Rob Mcconnell, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Persistent organic pollutants (POPs) are lipophilic environmental contaminants accumulated in the adipose tissue. Weight loss interventions, such as bariatric surgery, can mobilize POPs from adipose tissue into the bloodstream. We hypothesized that this mobilization could contribute to increases in blood pressure among 57 adolescents with severe obesity undergoing bariatric surgery. POPs and metabolic features were measured from visceral adipose tissue collected during surgery using gas and liquid chromatography, coupled with high-resolution mass spectrometry. Blood pressure was assessed at baseline, 6 months, and 5 years post-surgery. We used quantile g-computation to estimate associations of POP mixtures with blood pressure changes. With …

Molecular Identification Of The Italian Soldiers Found In The Second World War Mass Grave Of Ossero, Barbara Di Stefano, Barbara Bertoglio, Filomena Melchionda, Monica Concato, Solange Sorçaburu Ciglieri, Alessandro Bosetti, Pierangela Grignani, Eros Azzalini, Yasmine Addoum, Raffaella Vetrini, Fabiano Gentile, Francesco Introna, Serena Bonin, Chiara Turchi, Carlo Previderè, Paolo Fattorini

Faculty, Staff and Students Publications

Background/objectives: DNA analysis is the most reliable method for the identification of human skeletal remains, especially the ones found in mass disasters or recovered from mass graves. To this aim, DNA was extracted from bones and teeth allegedly belonging to 27 Italian soldiers executed during the Second World War and exhumed from a mass grave in Ossero (Croatia).

Methods: A selection of 131 different bone samples (petrous bones, femurs, metacarpal, and metatarsal bones) and 16 molar teeth were used for DNA extraction. Autosomal and Y-chromosome STR profiles were determined using a conventional CE approach, while a panel of 76 microhaplotypes …

Autism- And Intellectual Disability-Associated Myt1l Mutation Alters Human Cortical Interneuron Differentiation, Maturation, And Physiology, Ramachandran Prakasam, Julianna Determan, Gareth Chapman, Mishka Narasimhan, Renata Shen, Maamoon Saleh, Komal Kaushik, Paul Gontarz, Kesavan Meganathan, Bilal Hakim, Bo Zhang, James E Huettner, Kristen L Kroll

2020-Current year OA Pubs

Myelin transcription factor 1 like (MYT1L) is a neuronal transcription factor highly expressed in the developing and adult brain, and, while pathogenic MYT1L mutations cause neurodevelopmental disorders, these have not been characterized in human models of neurodevelopment. Here, we modeled the consequences of pathogenic MYT1L mutation using human stem cell-derived cortical neurons, demonstrating that MYT1L mutation alters the differentiation trajectory, increasing neuronal gene expression, morphological complexity, and synapse production. We also examined consequences of MYT1L mutation in mature cortical interneurons, identifying hallmarks of impaired neuronal identity and maturation and correspondingly altered channel expression and electrophysiological properties. Finally, by defining MYT1L …

Tracking And Mitigating Imprint Erasure During Induction Of Naive Human Pluripotency At Single-Cell Resolution, Laura A Fischer, Brittany Meyer, Monica Reyes, Joseph E Zemke, Jessica K Harrison, Kyoung-Mi Park, Ting Wang, Harald Jüppner, Sabine Dietmann, Thorold W Theunissen

2020-Current year OA Pubs

Naive human pluripotent stem cells (hPSCs) model the pre-implantation epiblast. However, parent-specific epigenetic marks (imprints) are eroded in naive hPSCs, which represents an important deviation from the epiblast in vivo. To track the dynamics of imprint erasure during naive resetting in real time, we established a dual-colored fluorescent reporter at both alleles of the imprinted SNRPN locus. During primed-to-naive resetting, SNRPN expression becomes biallelic in most naive cells, and biallelic SNRPN expression is irreversible upon re-priming. We utilized this live-cell reporter to evaluate chemical and genetic strategies to minimize imprint erasure. Decreasing the level of MEK/ERK inhibition or overexpressing the …

Structural Basis For Dimerization And Activation Of Uvrd-Family Helicases, Ankita Chadda, Binh Nguyen, Timothy M Lohman, Eric A Galburt

2020-Current year OA Pubs

UvrD-family helicases are superfamily 1A motor proteins that function during DNA replication, recombination, repair, and transcription. UvrD family monomers translocate along single-stranded (ss) DNA but need to be activated by dimerization to unwind DNA in the absence of force or accessory factors. However, prior structural studies have only revealed monomeric complexes. Here, we report the first structures of a dimeric UvrD-family helicase,

Simvastatin And Rifaximin In Decompensated Cirrhosis: A Randomized Clinical Trial, Elisa Pose, César Jiménez, Giacomo Zaccherini, Daniela Campion, Salvatore Piano, Frank Erhard Uschner, Koos De Wit, Olivier Roux, Kohilan Gananandan, Wim Laleman, Cristina Solé, Sonia Alonso, Berta Cuyàs, Xavier Ariza, Adrià Juanola, Ann T Ma, Laura Napoleone, Jordi Gratacós-Ginès, Marta Tonon, Enrico Pompili, Jordi Sánchez-Delgado, Andrew S Allegretti, Manuel Morales-Ruiz, Marta Carol, Martina Pérez-Guasch, Núria Fabrellas, Judit Pich, Claudia Martell, María Joyera, Gemma Domenech, José Ríos, Ferrán Torres, Miquel Serra-Burriel, Rubén Hernáez, Elsa Solà, Isabel Graupera, Hugh Watson, Germán Soriano, Rafael Bañares, Rajeshwar P Mookerjee, Claire Francoz, Ulrich Beuers, Jonel Trebicka, Paolo Angeli, Carlo Alessandria, Paolo Caraceni, Víctor M Vargas, Juan G Abraldes, Patrick S Kamath, Pere Ginès

Faculty, Staff and Students Publications

Importance: There are no useful treatments to prevent the development of severe complications of liver cirrhosis. Simvastatin and rifaximin have shown beneficial effects in liver cirrhosis.

Objective: To assess whether simvastatin combined with rifaximin improves outcomes in patients with decompensated cirrhosis.

Design, setting, and participants: Double-blind, placebo-controlled, phase 3 trial conducted among patients with decompensated cirrhosis in 14 European hospitals between January 2019 and December 2022. The last date of follow-up was December 2022.

Interventions: Patients were randomly assigned to receive simvastatin, 20 mg/d, plus rifaximin, 1200 mg/d (n = 117), or identical-appearing placebo (n = 120) for 12 months …

Resilience And Its Association With Hopelessness, Depression, Loneliness, Post-Traumatic Stress Disorder (Ptsd) And Suicidal Ideations And Behavior In A Cohort In The Nairobi Metropolitan, David M Ndetei, Victoria Mutiso, Christine Musyimi, Eric Jeremiah, Pascalyne Nyamai, Samuel Walusaka, Veronica Onyango, Kamaldeep Bhui, Daniel Mamah

2020-Current year OA Pubs

Comprehending resilience in the face of mental health issues is important, especially for young people who deal with a variety of psychological pressures. This study aims to investigate the co-occurrence of several mental health conditions and the role of resilience as a potential intervention in youth 14-25 years in the Nairobi metropolitan area. We recruited 1,972 youths. The following self-administered instruments were used: resilience (ARM-R), hopelessness (BHS), depression (BDI, PHQ-9), PTSD (HTQ), loneliness (UCLA Loneliness Scale) and suicidality (C-SSRS). Descriptive statistics, Pearson correlation and hierarchical multiple regression analyses were conducted on the data. The key findings are that depression and …

Transcriptome Complexity Disentangled: A Regulatory Molecules Approach, Amir Asiaee, Zachary B Abrams, Heather H Pua, Kevin R Coombes

2020-Current year OA Pubs

Transcription factors (TFs) and microRNAs (miRNAs) are fundamental regulators of gene expression, cell state, and biological processes. This study investigated whether a small subset of TFs and miRNAs could accurately predict genome-wide gene expression. We analyzed 8895 samples across 31 cancer types from The Cancer Genome Atlas and identified 28 miRNA and 28 TF clusters using unsupervised learning. Medoids of these clusters could differentiate tissues of origin with 92.8% accuracy, demonstrating their biological relevance. We developed Tissue-Agnostic and Tissue-Aware models to predict 20,000 gene expressions using the 56 selected medoid miRNAs and TFs. The Tissue-Aware model attained an R2 of …

Recessive Genetic Contribution To Congenital Heart Disease In 5,424 Probands, Weilai Dong, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the recessive contribution to the broad range of CHD phenotypes has been limited. We analyzed whole exome sequences of 5,424 CHD probands. Rare damaging RGs were estimated to contribute to at least 2.2% of CHD, with greater enrichment among laterality phenotypes (5.4%) versus other subsets (1.4%). Among 108 curated human recessive CHD genes, there were 66 RGs, with 54 in 11 genes with >1 RG, 12 genes with 1 RG, and …

Treatment Patterns And Outcomes In Follicular Lymphoma With Pod24: An Analysis From The Leo Consortium, Jonathan R Day, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Progression of disease within 24 months of initial immunochemotherapy (POD24) is a negative prognostic factor for patients with follicular lymphoma (FL). There is no standard treatment after POD24. Assembling an academic-based cohort from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence, we evaluated patterns of care and outcomes for 220 patients with FL with POD24 and retained FL histology. Therapy after POD24 was heterogeneous, with no treatment category accounting for >25% of the total. Among patients initially treated with bendamustine-rituximab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was the predominant second-line choice (48%). Among patients initially treated with R-CHOP, …

Ibrutinib For Therapy Of Steroid-Refractory Chronic Graft-Versus-Host Disease: A Multicenter Real-World Analysis, Joseph Pidala, Iskra Pusic, Et Al.

2020-Current year OA Pubs

To examine the activity of ibrutinib in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after the US Food and Drug Administration approval, we conducted a multicenter retrospective study. Data were standardly collected (N = 270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), gastrointestinal (GI) (26%), lung (27%), liver (19%), genital (7%), and others (4.4%). The National Institutes of Health (NIH) severity was mild in 5.7%, moderate 42%, and severe 53%. Thirty-nine percent had overlap subtype. Karnofsky performance status (KPS) was ≥80% in 72%. The median prednisone was 0.21 mg/kg (0-2.27). Ibrutinib was started at a …

Confounding Factors Of Cervical Carcinogenesis And Cervical Cancer Health Disparity, Vivek Kumar Kashyap, Namita Sinha, Nadeem Zafar, Murali M. Yallapu, Santosh Kumar, Everardo Cobos, Subhash C. Chauhan

Research Symposium

Clinical studies show that cervical cancer is the most frequently detected cancer in women living with human immunodeficiency virus (HIV), which has been defined as an acquired immunodeficiency syndrome (AIDS). Women living with HIV are 6 times more likely to develop cervical cancer compared to the general population, and an estimated 5% of all cervical cancer cases are attributable to HIV. Studies suggest that several genes are involved in different molecular pathways, which can influence the vulnerability, severity, or advancement of cervical cancer in the presence of HIV and human papillomavirus (HPV) co-infection. Clinical studies have also shown levels of …

Successful Limb Salvage In A Severe Diabetic Foot Infection: A Case Study Of Aggressive Surgical Intervention And Grafting Technique, Stephanie N. Campbell, Amanda Killeen, Michael Sobolevsky

Research Symposium

Background: Severe necrotizing diabetic foot infections are known to have high morbidity, high amputation risk, and high complication rates. Efforts at preserving the limb require significant surgical efforts and lengthy wound care. This process is more complicated in patients with significant housing instability.

Case Presentation: A 53-year-old male with uncontrolled diabetes (A1c 7.9%), housing insecurity, food insecurity presented with severe necrotizing diabetic foot infection with ascending cellulitis, infectious hemorrhagic bullae, multi-compartment abscesses of the foot and anterior leg. It is known that patients with diabetes are at increased risk of both amputation and surgical interventions than patients without diabetes. This …

Did You Know?

Osmosis Magazine

Fun Facts about the ‘Science’ of Christmas

An Interview With Dr. Kitchen, Paxton Mills

Osmosis Magazine

“Understanding geology can save lives.”

Cool Coatings For Cool People: What Sustainable Surfaces Can Do For You, Jack Dupuy

Osmosis Magazine

Climate change is forcing cities around the world to rethink their landscapes. Urban spaces, packed with concrete, asphalt, and rooftops, absorb more heat than rural areas, creating a phenomenon known as the Urban Heat Island (UHI) effect. This temperature rise stresses energy grids, shortens the lifespan of infrastructure, and makes city life more uncomfortable, particularly during summer months. Fortunately, cool coatings— innovative surface treatments designed to reflect sunlight and reduce heat absorption—are emerging as a solution to help cities beat the heat while saving energy and improving outdoor comfort.

Tower Of “Vietnam”: A Broader Version Of “Tower Of Hanoi”, Tien Nguyenchu

Osmosis Magazine

The traditional problem, “Tower of Hanoi”, might seem familiar to you. The “game” is believed to have been invented in 1883 by the French mathematician Édouard Lucas, although this fact is still disputed. In Vietnam (or sometimes India), there is a legend of a very tall temple with so many floors, and the floor’s diameter gets smaller as the temple gets higher. Priests would then lift each floor up, and move from one peg to another, using another peg as an auxiliary, such that no lower floor is smaller than the upper one. The legend said that once the priests …

Understanding The Theory Of Relativity: Simplified Space-Time, Xander Shelton

Osmosis Magazine

We’ve all heard of Albert Einstein and I’m sure most of us have heard of his theory of relativity. It’s a very popular concept that’s often talked about and mentioned, but what really is the theory of relativity? Well to understand it, first we have to get the backbone of the idea set up. The theory is composed of mainly two parts: Special Relativity and General Relativity. These two concepts are ideas that shaped scientific understanding of space, time, and gravity and fundamentally changed thinking in areas like atomic and nuclear physics in the 20th Century.

Why Can’T We Keep Making Antibiotics?, Kien Bui

Osmosis Magazine

Globally, the annual number of deaths due to antibiotic resistance infections is estimated to be 700,000, which can climb significantly with new viral diseases. The acquisition of antibiotic resistance in bacteria is a process related to the use of antibiotics to cure bacterial diseases. As bacteria replicate, mutations occur randomly, and there is a certain probability that this mutation introduces an antibiotic resistant gene. Upon exposure to antibiotics, all bacteria are cleared out, except for the ones that are antibiotic resistant. In other words, antibiotics significantly increase the gene frequency of the antibiotic resistant gene, allowing these bacteria to grow …

When Sense Start To Fade: Understanding Schizophrenia In The Blind And Deaf-Blind Communities, Bezawit Mulatu

Osmosis Magazine

Can Congenital Blindness Protect Against Schizophrenia While Gradual Loss of Sight and Hearing Heightens Vulnerability?

Exercise As A Drug: The Pharmacological Benefits Of Muscular Endurance Training For Type Ii Diabetes, Zack Ruighaver

Osmosis Magazine

In the United States, between 34 and 36 million people suffer from type II diabetes. That’s a little more than 1 in 10 Americans. Although type II diabetes typically develops in people 45 or older, cases are appearing more frequently in younger populations. But what if I told you that there was a drug that could help reverse this trend? No, I’m not talking about metformin or Ozempic. I’m talking about exercise – more specifically, muscular endurance training.

Would You Push The Fat Man? What Psychology Tells Us About Morality, Sam Chanenson

Osmosis Magazine

You’re on an out-of-control trolley hurtling towards five pedestrians trapped on the track ahead of you. While you can’t slow down, you notice just in time that if you flip a switch, you can jump to a parallel track. But oh no! On that track, another pedestrian is trapped. Quick! What do you do?

Mbti Results And Stereotypes: Should We Trust Them Or Not?, Sarah Su

Osmosis Magazine

The Myers-Briggs Type Indicator (MBTI), is a popular personality test that’s been around for decades. With a huge test taking population, it is a personality test well known and generally accepted by the public (Delgado, 2023). It is almost everywhere, from day to day conversations to its presence in social media, to even workplaces, where managers are using it as a tool to simplify complex human interactions (Essig, 2014). This means a huge population is using it to determine individual personalities and seeking connections within the society.

A Scientist's Guide To The Laboratory, Eve Snyder

Osmosis Magazine

“’You’re a scientist for goodness sake! What do you mean you don’t want to know why?’”

Letter From The Editor, Andrew Watts

Osmosis Magazine

Dear Reader,

Thank you for opening Osmosis Magazine. We are excited to bring you more accessible, intriguing stories in science and technology spanning the disciplines of biology, chemistry, psychology, and mathematics as well as faculty interviews.

Our goal as a magazine is to share the joy of science with the UR community in an accessible and entertaining fashion. We hope that you enjoy reading this Fall edition of Osmosis Magazine.

Finally, this is the last edition where I will serve as Editor in Chief. It has been a pleasure to work on this project with so many talented writers and …

Osmosis Magazine - Fall 2024

Osmosis Magazine

Osmosis is a student read, led, and written publication from the University of Richmond, focusing on all aspects of healthcare and science.