Medicine and Health Sciences Commons^™

A Framework For Detecting Noncoding Rare-Variant Associations Of Large-Scale Whole-Genome Sequencing Studies, Zilin Li, Xihao Li, Hufeng Zhou, Sheila M. Gaynor, Margaret Sunitha Selvaraj, Theodore Arapoglou, Corbin Quick, John Blangero, Joanne E. Curran, Ravindranath Duggirala, Harald H. H. Goring

School of Medicine Publications

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate …

Endovascular Therapy Vs Medical Management For Patients With Acute Stroke With Medium Vessel Occlusion In The Anterior Circulation, Hamidreza Saber, Shashvat M. Desai, Diogo C. Haussen, Alhamza R. Al-Bayati, Shahram Majidi, J. Mocco, Ameer E. Hassan, Gary Rajah, Muhammad Waqas, Jason Davies

School of Medicine Publications

Importance Randomized clinical trials have shown the efficacy of endovascular therapy (EVT) for acute large vessel occlusion strokes. The benefit of EVT in acute stroke with distal, medium vessel occlusion (DMVO) remains unclear.

Objective To examine the efficacy and safety outcomes associated with EVT in patients with primary DMVO stroke when compared with a control cohort treated with medical management (MM) alone.

Design, Setting, and Participants This multicenter, retrospective cohort study pooled data from patients who had an acute stroke and a primary anterior circulation emergency DMVO, defined as any segment of the anterior cerebral artery (ACA) or distal middle …

Lipoprotein Profiles Of Fat Distribution And Its Association With Insulin Sensitivity, Dongmei Wei, Vannina González Marrachelli, Jesus D. Melgarejo, Chia-Te Liao, Stefan Janssens, Peter Verhamme, Thomas Vanassche, Lucas Van Aelst, Daniel Monleon, Josep Redon, Zhen-Yu Zhang

School of Medicine Publications

Background: Fat deposition is associated with adverse outcomes. Waist-to-hip (WHR) ratio is a simple feasible index to assess fat distribution. Lipoprotein particle composition in relation to WHR and to what extent their association is mediated by insulin sensitivity are less investigated.

Methods: In 504 randomly recruited Flemish (mean age: 48.9 years; women: 51.6%), we analyzed the lipoprotein particle constitutions using nuclear magnetic resonance spectroscopy. WHR obesity described a WHR of ≥ 0.85 for women or 0.9 for men. Insulin sensitivity was evaluated by the homeostasis model assessment-estimated insulin resistance (HOMA-IR). SCORE-2 risk algorithm was applied to estimate 10-year cardiovascular risk. …

Monodelphis Domestica Induced Pluripotent Stem Cells Reveal Metatherian Pluripotency Architecture, Satish Kumar, Erica De Leon, Jose C. Granados, Deanne J. Whitworth, Jane F. Vandeberg

School of Medicine Publications

Marsupials have been a powerful comparative model to understand mammalian biology. However, because of the unique characteristics of their embryology, marsupial pluripotency architecture remains to be fully understood, and nobody has succeeded in developing embryonic stem cells (ESCs) from any marsupial species. We have developed an integration-free iPSC reprogramming method and established validated iPSCs from two inbred strains of a marsupial, Monodelphis domestica. The monoiPSCs showed a significant (6181 DE-genes) and highly uniform (r2 [95% CI] = 0.973 ± 0.007) resetting of the cellular transcriptome and were similar to eutherian ESCs and iPSCs in their overall transcriptomic profiles. …

Two Cases Of Autoimmune Syndrome Induced By Adjuvants (Asia): A Multifaceted Condition Calling For A Multidisciplinary Approach, Christine E. Loftis, Aidee Nunez, Mauricio De La Garza, Emilia C. Dulgheru

School of Medicine Publications

Silicone implants have been used for cosmetic enhancement and reconstructive purposes for over 60 years. Despite assiduous efforts to ensure safety, there is continuous evidence that they are not as biologically inert as previously postulated. We present two cases of autoimmune syndrome induced by adjuvants (ASIA) in Hispanic women. The first patient developed biopsy-proven immune-mediated necrotizing myopathy that was successfully treated with the combination of silicone explantation along with immunosuppressive therapy. Findings after implant removal demonstrated rupture and leakage of silicone from gluteal implants. The second patient developed autoimmune hemolytic anemia in the setting of a ruptured silicone breast implant. …

Two Cases Of Autoimmune Syndrome Induced By Adjuvants (Asia): A Multifaceted Condition Calling For A Multidisciplinary Approach, Christine Loftis, Aidee C. Nunez, Mauricio De La Garza, Emilia C. Dulgheru

School of Medicine Publications

Silicone implants have been used for cosmetic enhancement and reconstructive purposes for over 60 years. Despite assiduous efforts to ensure safety, there is continuous evidence that they are not as biologically inert as previously postulated. We present two cases of autoimmune syndrome induced by adjuvants (ASIA) in Hispanic women. The first patient developed biopsy-proven immune-mediated necrotizing myopathy that was successfully treated with the combination of silicone explantation along with immunosuppressive therapy. Findings after implant removal demonstrated rupture and leakage of silicone from gluteal implants. The second patient developed autoimmune hemolytic anemia in the setting of a ruptured silicone breast implant. …

Whole Genome Sequence Analysis Of Blood Lipid Levels In >66,000 Individuals, Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Akhil Pampana, David Y. Zhang, Joanne E. Curran, Ravi Duggirala, John Blangero, Juan M. Peralta, Harald Hh Goring, Michael Mahaney

School of Medicine Publications

Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid …

Shared Brain And Genetic Architectures Between Mental Health And Physical Activity, Wei Zhang, Sarah E. Paul, Anderson M. Winkler, Ryan Bogdan, Janine D. Bijsterbosch

School of Medicine Publications

Physical activity is correlated with, and effectively treats various forms of psychopathology. However, whether biological correlates of physical activity and psychopathology are shared remains unclear. Here, we examined the extent to which the neural and genetic architecture of physical activity and mental health are shared. Using data from the UK Biobank (N = 6389), we applied canonical correlation analysis to estimate associations between the amplitude and connectivity strength of subnetworks of three major neurocognitive networks (default mode, DMN; salience, SN; central executive networks, CEN) with accelerometer-derived measures of physical activity and self-reported mental health measures (primarily of depression, anxiety …

Predictive Performance And Clinical Application Of Cov50, A Urinary Proteomic Biomarker In Early Covid-19 Infection: A Prospective Multicentre Cohort Study, Jan A. Staessen, Ralph Wendt, Yu-Ling Yu, Sven Kalbitz, Lutgarde Thijs, Justyna Siwy, Julia Raad, Jochen Metzger, Barbara Neuhaus, Gladys E. Maestre

School of Medicine Publications

Background: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker.

Methods: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis …

Two Cases Of Autoimmune Syndrome Induced By Adjuvants (Asia): A Multifaceted Condition Calling For A Multidisciplinary Approach, Christine Loftis, Aidee C. Nunez, Mauricio De La Garza, Emilia Dulgheru

School of Medicine Publications

Silicone implants have been used for cosmetic enhancement and reconstructive purposes for over 60 years. Despite assiduous efforts to ensure safety, there is continuous evidence that they are not as biologically inert as previously postulated. We present two cases of autoimmune syndrome induced by adjuvants (ASIA) in Hispanic women. The first patient developed biopsy-proven immune-mediated necrotizing myopathy that was successfully treated with the combination of silicone explantation along with immunosuppressive therapy. Findings after implant removal demonstrated rupture and leakage of silicone from gluteal implants. The second patient developed autoimmune hemolytic anemia in the setting of a ruptured silicone breast implant. …

Tdcs Induced Gaba Change Is Associated With The Simulated Electric Field In M1, An Effect Mediated By Grey Matter Volume In The Mrs Voxel, Tulika Nandi, Oula Puonti, William T. Clarke, Caroline Nettekoven, Helen C. Barron, James Kolasinski, Taylor Hanayik, Emily L. Hinson, Adam Berrington, Anderson M. Winkler

School of Medicine Publications

Background and objective

Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect.

Methods

Data from five previously conducted MRS …

The Ccr2+ Monocyte Subsets Increase In Obese Boys But Not Girls With Abnormally High Carotid Intima-Media Thickness: A Pilot Study, María José Garcés-Hernández, Karen Pedraza-Escudero, Nayely Garibay-Nieto, Joselin Hernández-Ruiz, Jessica Lakshmi Prieto-Chávez, Lourdes Andrea Arriaga-Pizano, Eréndira Villanueva-Ortega, Galileo Escobedo, Aaron Noe Manjarrez-Reyna, Juan C. Lopez-Alvarenga

School of Medicine Publications

The differential contribution of monocyte subsets expressing the C-C chemokine receptor 2 (CCR2) to subclinical atherosclerosis in girls and boys is unclear. In this pilot study, we compared classical, intermediate, and nonclassical monocyte subsets expressing CCR2 in 33 obese children of both sexes aged 8 to 16 divided by carotid intima-media thickness (IMT), considering values above the 75th percentile (p75) as abnormally high IMT. Obesity was defined as body mass index above the 95th percentile according to age and sex. Flow cytometry analyses revealed that boys but not girls with IMT ≥ p75 displayed increased CCR2⁺ cell percentage and …

Chronic Neuropsychiatric Sequelae Of Sars-Cov-2: Protocol And Methods From The Alzheimer's Association Global Consortium, Gabriel A. De Erausquin, Heather Snyder, Traolach S. Brugha, Sudha Seshadri, Maria Carrillo, Rajesh Sagar, Yueqin Huang, Charles Newton, Carmela Tartaglia, John Blangero, Gladys E. Maestre, Sarah Williams Blangero

School of Medicine Publications

Introduction

Coronavirus disease 2019 (COVID‐19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID‐19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID‐19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity …

Metabolic Syndrome Predictors Of Brain Gray Matter Volume In An Age-Stratified Community Sample Of 776 Mexican- American Adults: Results From The Genetics Of Brain Structure Image Archive, Eithan Kotkowski, Larry R. Price, Ralph A. Defronzo, Crystal G. Franklin, Maximino Salazar, Amy S. Garrett, Mary Woolsey, John Blangero, Ravi Duggirala, David C. Glahn, Peter T. Fox

School of Medicine Publications

Introduction: This project aimed to investigate the association between biometric components of metabolic syndrome (MetS) with gray matter volume (GMV) obtained with magnetic resonance imaging (MRI) from a large cohort of community-based adults (n = 776) subdivided by age and sex and employing brain regions of interest defined previously as the “Neural Signature of MetS” (NS-MetS).

Methods: Lipid profiles, biometrics, and regional brain GMV were obtained from the Genetics of Brain Structure (GOBS) image archive. Participants underwent T1-weighted MR imaging. MetS components (waist circumference, fasting plasma glucose, triglycerides, HDL cholesterol, and blood pressure) were defined using the National Cholesterol …

Genome-Wide Association Analyses Of Physical Activity And Sedentary Behavior Provide Insights Into Underlying Mechanisms And Roles In Disease Prevention, Zhe Wang, Andrew Emmerich, Nicolas J. Pillon, Tim Moore, Daiane Hemerich, Marilyn C. Cornelis, Eugenia Mazzaferro, Siacia Broos, Tarunveer S. Ahluwalia, John Blangero

School of Medicine Publications

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle …

Prolactin Expression In The Baboon (Papio Hamadryas) Eye, María Lourdes Garza-Rodríguez, Iram Pablo Rodriguez-Sanchez, Rafael Gonzalez-Alvarez, Maricela Luna, Carlos H. Burciaga-Flores, Fernando Alcorta-Nuñez, Orlando Solis-Coronado, Victor Manuel Bautista De Lucio, Genaro A. Ramírez-Correa, Oscar Vidal-Gutierrez, Diana Cristina Perez-Ibave

School of Medicine Publications

Simple Summary

Covid-19 And Vaccination: Myths Vs Science, Vivek P. Chavda, Yangmin Chen, Jayant Dave, Zhe-Sheng Chen, Subhash C. Chauhan, Murali M. Yallapu, Vladimir N. Uversky, Rajashri Bezbaruah, Sandip Patel, Vasso Apostolopoulos

School of Medicine Publications

Introduction: Several vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed since the inception of the coronavirus disease 2019 (COVID-19) in December 2019, at unprecedented speed. However, these rapidly developed vaccines raised many questions related to the efficacy and safety of vaccines in different communities across the globe. Various hypotheses regarding COVID-19 and its vaccines were generated, and many of them have also been answered with scientific evidence. Still, there are many myths/misinformation related to COVID-19 and its vaccines, which create hesitancy for COVID-19 vaccination, and must be addressed critically to achieve success in the battle against …

Risk Of Suicide In Patients With Major Depressive Disorder And Comorbid Chronic Pain Disorder: An Insight From National Inpatient Sample Data, Taranjeet Jolly, Ramu Vadukapuram, Chintan Trivedi, Zeeshan Mansuri, Mahwish Adnan, Steven P. Cohen, To-Nho Vu

School of Medicine Publications

Background: Approximately 17.3 million adults in the United States have had a minimum of one major depressive episode. Comorbidity of depression and pain can affect individuals of any age, but is more prevalent in the elderly affecting up to 13% of people in the elderly population. Given that depression and suicidal ideation (SI) pose a considerable burden resulting in enormous suffering, there is a need to understand the factors of the relationship between chronic pain (CP), depression, and SI.

Objectives: Our primary objective in this study was to compare suicidality (SI/attempt [SA]) between patients with major depressive disorder (MDD) and …

Periprosthetic Knee Infection After Benign Tumor Excision Complicated By Carbapenem Resistant Enterobacteriaceae: A Case Report, Jennifer Adams, Daniel Habenicht, Duncan Ramsey

School of Medicine Publications

Introduction

Periprosthetic joint infection (PJI) is a major complication after total knee arthroscopy. Enterobacter is a rare cause of PJI.

Case presentation

We present a 65 year old Caucasian man who presented with acute right knee PJI with Carbapenem-resistant Enterobacteriaceae (CRE) two months after undergoing right knee intra-articular mass removal with endoprosthetic reconstruction. The periprosthetic joint infection (PJI) was treated with revision with 1-stage static spacer and IV meropenem.

Discussion

CRE is an uncommon cause of PJI, but when it does occur, it commonly infects patients who are immunosuppressed or have specific risk factors. For an immunocompetent patient …

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 …

Diagnosing A Rare Thoracic Intramedullary Spinal Dermoid Cyst Using Dwi With Adc Mapping: Case Report, Jennifer Adams, Daniel Habenicht, Sohum Desai

School of Medicine Publications

Introduction

Dermoid cysts are rare lesions generally associated with embryological errors that occur during neural tube closure. Intramedullary lesions are extremely rare, especially within the upper thoracic spinal cord.

Case presentation

We report a case of a 19-year-old male who had an intramedullary thoracic dermoid cyst presenting with progressive ataxia, lower limb weakness, and hyperreflexia. MRI demonstrated a 1.2 × 1.8-cm intramedullary thoracic dermoid cyst causing significant spinal cord compression, which was successfully removed via full resection. The patient had an uncomplicated postoperative course, with improvement in preoperative deficits.

Discussion

This is a unique case documenting a thoracic spinal cord …

Microrna-205 In Prostate Cancer: Overview To Clinical Translation, Neeraj Chauhan, Anjali Manojkumar, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

Prostate cancer (PrCa) is one of the most common types of cancer among men in the United States. The metastatic and advanced PrCa develops drug resistance to current regimens which accounts for the poor management. microRNAs (miRNAs) have been well-documented for their diagnostic, prognostic, and therapeutic roles in various human cancers. Recent literature confirmed that microRNA-205 (miR-205) has been established as one of the tumor suppressors in PrCa. miR-205 regulates number of cellular functions, such as proliferation, invasion, migration/metastasis, and apoptosis. It is also evident that miR-205 can serve as a key biomarker in diagnostic, prognostic, and therapy of PrCa. …

Structural Brain Correlates Of Childhood Inhibited Temperament: An Enigma-Anxiety Mega-Analysis, Janna Marie Bas-Hoogendam, Rachel Bernstein, Brenda E. Benson, Kristin A. Buss, Kelley E. Gunther, Koraly Pérez-Edgar, Giovanni A. Salum, Andrea P. Jackowski, Rodrigo A. Bressan, Anderson M. Winkler

School of Medicine Publications

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).2 IT is a moderately heritable trait1 that can be measured in multiple species.3 In humans, levels of IT can be quantified from the first year of life through …

Epithelial Immunomodulation By Aerosolized Toll-Like Receptor Agonists Prevents Allergic Inflammation In Airway Mucosa In Mice, David L. Goldblatt, Gabriella Valverde Ha, Shradha Wali, Vikram V. Kulkarni, Michael K. Longmire, Ana M. Jaramillo, Rosha P. Chittuluru, Adrienne Fouts, Margarita Martinez-Moczygemba, Jonathan T. Lei

School of Medicine Publications

Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells …

Multi-Omics Analysis Reveals Metabolic And Epigenetic Changes Associated With Macrophage Polarization, Mark L. Sowers, Hui Tang, Vipul K. Singh, Arshad Khan, Abhishek Mishra, Blanca I. Restrepo, Chinnaswamy Jagannath, Kangling Zhang

School of Medicine Publications

Macrophages (MФ) are an essential immune cell for defense and repair that travel to different tissues and adapt based on local stimuli. A critical factor that may govern their polarization is the cross-talk between metabolism and epigenetics. However, simultaneous measurements of metabolites, epigenetics, and proteins (phenotype) has been a major technical challenge. To address this, we have developed a novel triomics approach using mass spectrometry to comprehensively analyze metabolites, proteins, and histone modifications, in a single sample. To demonstrate this technique, we investigated the metabolic-epigenetic-phenotype axis following polarization of human blood-derived monocytes into either 'pro-inflammatory M1'- or 'anti-inflammatory M2-' MФs. …

Optical Redox Imaging Of Ex Vivo Hippocampal Tissue Reveals Age-Dependent Alterations In The 5xfad Mouse Model Of Alzheimer's Disease, He N. Xu, Sarah Gourmaud, Allison Podsednik, Xiaofan Li, Huaqing Zhao, Frances E. Jensen, Delia M. Talos, Lin Z. Li

School of Medicine Publications

A substantial decline in nicotinamide adenine dinucleotide (NAD) has been reported in brain tissue homogenates or neurons isolated from Alzheimer's disease (AD) models. NAD, together with flavin adenine dinucleotide (FAD), critically supports energy metabolism and maintains mitochondrial redox homeostasis. Optical redox imaging (ORI) of the intrinsic fluorescence of reduced NAD (NADH) and oxidized FAD yields cellular redox and metabolic information and provides biomarkers for a variety of pathological conditions. However, its utility in AD has not been characterized at the tissue level. We performed ex vivo ORI of freshly dissected hippocampi from a well-characterized AD mouse model with five familial …

The Genetic Contribution To Solving The Cocktail-Party Problem, Samuel R. Mathias, Emma Knowles, Josephine Mollon, Amanda Rodrigue, Mary K. Woolsey, Rene L. Olvera, Juan M. Peralta, Satish Kumar, Harald H. H. Goring, Ravi Duggirala, Joanne E. Curran, John Blangero, David C. Glahn

School of Medicine Publications

Communicating in everyday situations requires solving the cocktail-party problem, or segregating the acoustic mixture into its constituent sounds and attending to those of most interest. Humans show dramatic variation in this ability, leading some to experience real-world problems irrespective of whether they meet criteria for clinical hearing loss. Here, we estimated the genetic contribution to cocktail-party listening by measuring speech-reception thresholds (SRTs) in 425 people from large families and ranging in age from 18 to 91 years. Roughly half the variance of SRTs was explained by genes (h 2 = 0.567). The genetic correlation between SRTs and hearing thresholds …

Whole Genome Association Study Of The Plasma Metabolome Identifies Metabolites Linked To Cardiometabolic Disease In Black Individuals, Usman A. Tahir, Daniel H. Katz, Julian Avila-Pachecho, Alexander G. Bick, Akhil Pampana, John Blangero, Joanne Curran, Juan M. Peralta, Harald H. H. Goring, Michael Mahaney

School of Medicine Publications

Integrating genetic information with metabolomics has provided new insights into genes affecting human metabolism. However, gene-metabolite integration has been primarily studied in individuals of European Ancestry, limiting the opportunity to leverage genomic diversity for discovery. In addition, these analyses have principally involved known metabolites, with the majority of the profiled peaks left unannotated. Here, we perform a whole genome association study of 2,291 metabolite peaks (known and unknown features) in 2,466 Black individuals from the Jackson Heart Study. We identify 519 locus-metabolite associations for 427 metabolite peaks and validate our findings in two multi-ethnic cohorts. A significant proportion of these …

Detection Of Pancreatic Cancer Mirna With Biocompatible Nitrogen-Doped Graphene Quantum Dots, Ryan Ajgaonkar, Bong Lee, Alina Valimukhametova, Steven Nguyen, Roberto Gonzalez-Rodriguez, Jeffery Coffer, Giridhar R. Akkaraju, Anton V. Naumov

School of Medicine Publications

Early-stage pancreatic cancer remains challenging to detect, leading to a poor five-year patient survival rate. This obstacle necessitates the development of early detection approaches based on novel technologies and materials. In this work, the presence of a specific pancreatic cancer-derived miRNA (pre-miR-132) is detected using the fluorescence properties of biocompatible nitrogen-doped graphene quantum dots (NGQDs) synthesized using a bottom-up approach from a single glucosamine precursor. The sensor platform is comprised of slightly positively charged (1.14 ± 0.36 mV) NGQDs bound via π-π stacking and/or electrostatic interactions to the negatively charged (-22.4 ± 6.00 mV) bait ssDNA; together, they form a …

Keeping 21st Century Paleontology Grounded: Quantitative Genetic Analyses And Ancestral State Reconstruction Re-Emphasize The Essentiality Of Fossils, Tesla A. Monson, Marianne F. Brasil, Michael Mahaney, Christopher A. Schmitt, Catherine E. Taylor, Leslea J. Hlusko

School of Medicine Publications

Advances in genetics and developmental biology are revealing the relationship between genotype and dental phenotype (G:P), providing new approaches for how paleontologists assess dental variation in the fossil record. Our aim was to understand how the method of trait definition influences the ability to reconstruct phylogenetic relationships and evolutionary history in the Cercopithecidae, the Linnaean Family of monkeys currently living in Africa and Asia. We compared the two-dimensional assessment of molar size (calculated as the mesiodistal length of the crown multiplied by the buccolingual breadth) to a trait that reflects developmental influences on molar development (the inhibitory cascade, IC) and …