Medicine and Health Sciences Commons^™

Reduced Bacterial Burden Of The Skin Surrounding The Shoulder Joint Following Topical Protocatechuic Acid Application: Results Of A Pilot Study, Omid Jalali, Molly Best, Alison Wong, Brett Schaeffer, Brendon Bauer, Lanny Johnson

Faculty, Staff and Students Publications

BACKGROUND: Reducing the rising health-care burden associated with shoulder surgical site infection (SSI) is of paramount importance. The purpose of this study was to investigate the antimicrobial efficacy of protocatechuic acid (PCA) as a topical reagent for surgical skin antisepsis surrounding the shoulder joint.

METHODS: This was a 2-phase skin-disinfection trial involving the human shoulder. The shoulders of healthy volunteers were randomized to topical treatment with PCA (a 10% concentration of PCA in Phase I [11 subjects] and a 17% concentration in Phase II [12 subjects]), with a control of isopropyl alcohol (IPA) applied to the contralateral shoulder. Mechanical scraping …

Protocatechuic Acid As A Topical Antimicrobial For Surgical Skin Antisepsis: Preclinical Investigations, Omid Jalali, Molly Best, Alison Wong, Brett Schaeffer, Brendon Bauer, Lanny Johnson

Faculty, Staff and Students Publications

BACKGROUND: There is a need for novel skin antiseptic agents to combat the health-care burdens associated with surgical site infection (SSI) and bacterial resistance. The purpose of this proof-of-principle pilot study was to investigate the potential of the phenolic compound protocatechuic acid (PCA) as a topical antimicrobial for surgical skin antisepsis.

METHODS: The Kirby-Bauer method of disc diffusion was used to investigate the in vitro antimicrobial activity and comparative effectiveness of PCA and 7 related compounds against SSI pathogens. To explore the in vivo efficacy of topical PCA for providing deep, penetrating skin antisepsis, living

RESULTS: Compared with other polyphenols, …

Non-Uniformity Of Projection Distributions Attenuates Resolution In Cryo-Em, Philip R Baldwin, Dmitry Lyumkis

Faculty, Staff and Students Publications

Virtually all single-particle cryo-EM experiments currently suffer from specimen adherence to the air-water interface, leading to a non-uniform distribution in the set of projection views. Whereas it is well accepted that uniform projection distributions can lead to high-resolution reconstructions, non-uniform (anisotropic) distributions can negatively affect map quality, elongate structural features, and in some cases, prohibit interpretation altogether. Although some consequences of non-uniform sampling have been described qualitatively, we know little about how sampling quantitatively affects resolution in cryo-EM. Here, we show how inhomogeneity in any projection distribution scheme attenuates the global Fourier Shell Correlation (FSC) in relation to the number …

Pregnancy And Lactation In A 67-Year-Old Elderly Gravida Following Donor Oocyte, Leila Magistrado, Mary C Tolcher, Anju Suhag, Sonal Zambare, Kjersti M Aagaard

Faculty, Staff and Students Publications

There is limited data on the anticipated perinatal course among gravidae in their sixth and seventh decades. Our objective was to describe the relatively uncomplicated prenatal, intrapartum, and postpartum course of a 67-year-old essential primigravida. Briefly, our patient conceived a singleton pregnancy via IVF with donor oocytes, then presented at 13 6/7 weeks of gestation to initiate prenatal care. Her medical history was significant for chronic hypertension, hyperlipidemia, and obesity. Her cardiac function was monitored throughout pregnancy, and she delivered at 36 1/7 weeks by cesarean for a decline in left ventricular function with mitral regurgitation. Her intrapartum and postpartum …

Sirt3 Promotes Lipophagy And Chaperon-Mediated Autophagy To Protect Hepatocytes Against Lipotoxicity, Tian Zhang, Jingxin Liu, Shengnan Shen, Qiang Tong, Xiaojun Ma, Ligen Lin

Faculty, Staff and Students Publications

Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs) breakdown, to initiate lipolysis via either cytosolic lipases or macroautophagy. SIRT3, a mitochondrial NAD+-dependent deacetylase, regulates the acetylation status and activity of many substrates involving in energy metabolism. However, the role of SIRT3 in regulating lipophagy is controversial. The current study showed that SIRT3 expression was decreased and the macroautophagy flux was blocked in the primary hepatocytes from high-fat diet fed mice and P/O (palmitic acid and oleic acid mixture) treated AML12 mouse hepatocytes, compared with the corresponding controls. …

Extracellular Mitochondria Released From Traumatized Brains Induced Platelet Procoagulant Activity, Zilong Zhao, Yuan Zhou, Tristan Hilton, Fanjian Li, Cha Han, Li Liu, Hengjie Yuan, Ying Li, Xin Xu, Xiaoping Wu, Fangyi Zhang, Perumal Thiagarajan, Andrew Cap, Fu-Dong Shi, Jianning Zhang, Jing-Fei Dong

Faculty, Staff and Students Publications

Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant. In testing this hypothesis experimentally, we found that the extracellular mitochondria purified from brain trauma mice and those released from brains subjected to freeze-thaw injury remained metabolically active and produced reactive …

Lisinopril-Induced Angioedema In A Patient With Plasma Prekallikrein Deficiency, Swapan K Dasgupta, Stefanie Rivera, Perumal Thiagarajan

Faculty, Staff and Students Publications

Angiotensin-converting enzyme (ACE) inhibitors are extensively prescribed to treat patients with hypertension, congestive heart failure, and diabetic nephropathy. A small fraction of these patients (approximately 0.7%) develop angioedema, manifested by swelling of the lips and oropharynx. Angioedema of oropharynx is a medical emergency that can lead to asphyxiation and death. The angioedema is due to bradykinin generated from high molecular weight kininogen by kallikrein, which is derived from plasma prekallikrein by action of the factor XIIa, factor Xia, or prolylcarboxypeptidase. Bradykinin induces vasodilation and increased vascular permeability. ACE is the major degrading enzyme of bradykinin in the intravascular department. ACE …

A Remarkable Response Of Granulomatous Hypophysitis To Infliximab In A Patient With A Background Of Crohn's Disease-A Case Report, Bahar K Force, Tiphanie P Vogel, Dang M Nguyen, Kent A Heck, Sherly Sebastian, Mas Takashima, Daniel Yoshor, Susan L Samson

Faculty, Staff and Students Publications

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Aromatase Inhibitors Plus Weight Loss Improves The Hormonal Profile Of Obese Hypogonadal Men Without Causing Major Side Effects, Georgia Colleluori, Rui Chen, Christie G Turin, Francesca Vigevano, Clifford Qualls, Biju Johnson, Sanjay Mediwala, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).

Design: Randomized double-blind placebo-controlled pilot trial.

Methods: …

Development Of A Hybrid, Interprofessional, Interactive Quality Improvement Curriculum As A Model For Continuing Professional Development, Isabelle S Kusters, Megan E Gregory, Jennifer L Bryan, Sylvia J Hysong, Lechauncy D Woodard, Aanand D Naik, Kyler M Godwin

Faculty, Staff and Students Publications

Over the past 20 years, there has been an increased focus on quality improvement (QI) in health care, which is critical in achieving care that is patient-centered, safer, timelier, and more effective, efficient, and equitable. At the center of this movement is QI education, which is known to lead to learning, behavior change, and improved outcomes. However, there is a need for the development and provision of long-duration, interactive, interprofessional training in QI, to allow for in-depth learning and application of learned skills. To this end, we designed a curriculum for an established interprofessional, interactive, web-based QI fellowship for doctorally …

Perioperative Acute Kidney Injury, Sam D Gumbert, Felix Kork, Maisie L Jackson, Naveen Vanga, Semhar J Ghebremichael, Christy Y Wang, Holger K Eltzschig

Faculty, Staff and Students Publications

Perioperative organ injury is among the leading causes of morbidity and mortality of surgical patients. Among different types of perioperative organ injury, acute kidney injury occurs particularly frequently and has an exceptionally detrimental effect on surgical outcomes. Currently, acute kidney injury is most commonly diagnosed by assessing increases in serum creatinine concentration or decreased urine output. Recently, novel biomarkers have become a focus of translational research for improving timely detection and prognosis for acute kidney injury. However, specificity and timing of biomarker release continue to present challenges to their integration into existing diagnostic regimens. Despite many clinical trials using various …

The Longitudinal Parallel Process Analysis Of Biomarkers Of Oxidative Stress, Symptom Clusters, And Cognitive Function In Children With Leukemia, Mary C Hooke, Daniel Hatch, Marilyn J Hockenberry, Susan Whitman, Ida Moore, David Montgomery, Kari Marano, Pauline Mitby, Michael E Scheurer, Olga Taylor, Wei Pan

Faculty, Staff and Students Publications

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar …

The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz

Faculty, Staff and Students Publications

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling …

Metaproteomic Analysis Of Human Gut Microbiome In Digestive And Metabolic Diseases, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Metaproteomics, as a subfield of proteomics, has quickly emerged as a pivotal tool for global characterization of a microbiome system at a functional level. It has been increasingly applied in studying human digestive and metabolic diseases, and provides information-rich data to identify the dysbiosis of human gut microbiome related to healthy or disease states to elucidate the molecular events underlying host-microbiota interplays. While significant technical challenges still exist, this emerging technology has been demonstrated to provide essential information in interrogating functional changes in the human gut microbiome, complementary to metagenomics and metatranscriptomics. This chapter overviews the overall metaproteomic work flow …

Prevalence Of Chronic Hepatitis B In Oro Province, Papua New Guinea, Alice Unah Lee, Luke Mair, Bob Kevin, Lily Gandi, Olive Tarumuri, Caroline Lee, Sue Huntley, David Carl Hilmers

Faculty, Staff and Students Publications

Chronic hepatitis B (CHB) affects over 250 million people worldwide. In Papua New Guinea, the prevalence of CHB has been estimated to be over 8%, and it is a leading cause of death. To address this problem, an alliance was formed between the government of Oro Province, a large private employer and an Australian nongovernmental organization, which established a CHB test and treatment programme. Between 2014 and 2019, rapid hepatitis B surface antigen testing was performed on 4068 individuals in Oro Province. The crude prevalence rate was 12.98% and was significantly higher in males (15.26%) than females (10.94%) (P < 0.001). The rate was 4.72% among children aged 10 years and under, 12.81% among women of childbearing age (19–35 years) and 18.48% among health-care workers. These results indicate that the rates of vaccination at birth and later among women of childbearing age and health-care workers must be improved to prevent transmission of CHB.

Effectiveness Of A 24/7 Dad® Curriculum In Improving Father Involvement: Profiles Of Engagement, Roneé E Wilson, Renice Obure, Precious Omokaro, Hamisu M Salihu, Estrellita Lo Berry, Deborah A Austin, Jennifer G Christner

Faculty, Staff and Students Publications

BACKGROUND OR OBJECTIVES: Father involvement is a key component in maintaining healthy families and communities. This study presents quantitative results of the first five years of a comprehensive fatherhood training program offered by REACHUP, Inc. in Florida, United States.

METHODS: The program utilized the 24/7 Dad ® curriculum for the fatherhood training program. Key program outcome was differences in pre and post-test scores on self-awareness, fathering skills, parenting skills, relationship skills, and self-care. Demographic and pretest-posttest data collected between 2013 and 2017 were analyzed using chi-square test for categorical variables, McNemar's test for differences in proportions pre- and post-intervention, paired …

Acute Lymphoblastic Leukemia Presenting Initially As Spinal Cord Compression: When Chemotherapy Alone Is Enough, Albert Jang, Kallie N Kram, Scott N Berger, Mahmoud R Gaballa, Lee B Lu, David R Dunaway, Courtney N Miller-Chism

Faculty, Staff and Students Publications

Spinal cord compression (SCC) is a rare initial presentation and complication of acute lymphoblastic leukemia (ALL) with nearly all reported cases occurring in the pediatric population. We report a 38-year-old previously healthy man who presented with acute on chronic lower back pain, gait instability, urinary retention, and severe thrombocytopenia. Radiologic examination revealed two soft tissue masses of the thoracic spine associated with compression fractures causing spinal canal narrowing and cord compression. Bone marrow biopsy confirmed the diagnosis of ALL. Immediate initiation of high-dose corticosteroids and systemic chemotherapy resolved the patient's symptoms without radiation therapy or surgical intervention. After two courses …

Large Sinus Of Valsalva Aneurysm Complicated By Thrombus Formation, Milan Ravishankar, Ali Ghergherehchi, Jing Liu, Ernesto Jimenez, Umair Khalid

Faculty, Staff and Students Publications

Sinus of Valsalva aneurysm (SOVA) is an unusual cardiac anomaly that is potentially fatal with rupture. It is often asymptomatic but has various presentations. We describe a case of a 67-year-old male who presented with atypical chest pain. Transthoracic echocardiogram and cardiac computed tomography scan confirmed a large SOVA complicated by thrombus formation and compression of the left atrium and left ventricular outflow tract. The patient successfully underwent a Bentall procedure-surgical aortic aneurysm repair with mechanical aortic valve conduit. We discuss several clinical decision-making branch points to highlight the complexity of managing this condition. Even in asymptomatic or minimally symptomatic …

Hypogonadism, Type-2 Diabetes Mellitus, And Bone Health: A Narrative Review, Vittoria Russo, Rui Chen, Reina Armamento-Villareal

Faculty, Staff and Students Publications

One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could …

Single-Nuclei Rna-Seq On Human Retinal Tissue Provides Improved Transcriptome Profiling, Qingnan Liang, Rachayata Dharmat, Leah Owen, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Shaoheng Liang, Nathaniel Wu, Ken Chen, Margaret M Deangelis, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA-seq is a powerful tool in decoding the heterogeneity in complex tissues by generating transcriptomic profiles of the individual cell. Here, we report a single-nuclei RNA-seq (snRNA-seq) transcriptomic study on human retinal tissue, which is composed of multiple cell types with distinct functions. Six samples from three healthy donors are profiled and high-quality RNA-seq data is obtained for 5873 single nuclei. All major retinal cell types are observed and marker genes for each cell type are identified. The gene expression of the macular and peripheral retina is compared to each other at cell-type level. Furthermore, our dataset shows an …

Electrochemical Hydrogen Evolution Over Hydrothermally Synthesized Re-Doped Mos2 Flower-Like Microspheres, Juan Aliaga, Pablo Vera, Juan Araya, Luis Ballesteros, Julio Urzúa, Mario Farías, Francisco Paraguay-Delgado, Gabriel Alonso-Núñez, Guillermo González, Eglantina Benavente

Faculty, Staff and Students Publications

In this research, we report a simple hydrothermal synthesis to prepare rhenium (Re)- doped MoS2 flower-like microspheres and the tuning of their structural, electronic, and electrocatalytic properties by modulating the insertion of Re. The obtained compounds were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). Structural, morphological, and chemical analyses confirmed the synthesis of poorly crystalline Re-doped MoS2 flower-like microspheres composed of few stacked layers. They exhibit enhanced hydrogen evolution reaction (HER) performance with low overpotential of 210 mV at current density of 10 mA/cm2, with a …

Examining Multiple Cellular Pathways At Once Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken

Faculty, Staff and Students Publications

Sensitive simultaneous assessment of multiple signaling pathways within the same cells requires orthogonal reporters that can assay over large dynamic ranges. Luciferases are such genetically encoded candidates due to their sensitivity, versatility, and cost-effectiveness. We expand luciferase multiplexing in post-lysis endpoint luciferase assays from two to six. Light emissions are distinguished by a combination of distinct substrates and emission spectra deconvolution. All six luciferase reporter units are stitched together into one plasmid facilitating delivery of all reporter units through a process we termed solotransfection, minimizing experimental errors. We engineer a multiplex hextuple luciferase assay to probe pathway fluxes through five …

Residues And Residue Pairs Of Evolutionary Importance Differentially Direct Signaling Bias Of D2 Dopamine Receptors, María E Terrón-Díaz, Sara J Wright, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel

Faculty, Staff and Students Publications

The D2 dopamine receptor and the serotonin 5-hydroxytryptamine 2A receptor (5-HT2A) are closely-related G-protein–coupled receptors (GPCRs) from the class A bioamine subfamily. Despite structural similarity, they respond to distinct ligands through distinct downstream pathways, whose dysregulation is linked to depression, bipolar disorder, addiction, and psychosis. They are important drug targets, and it is important to understand how their bias toward G-protein versus β-arrestin signaling pathways is regulated. Previously, evolution-based computational approaches, difference Evolutionary Trace and Evolutionary Trace–Mutual information (ET-Mip), revealed residues and residue pairs that, when switched in the D2 receptor to the corresponding residues from 5-HT2A, altered ligand potency …

Ultrafast Two-Photon Imaging Of A High-Gain Voltage Indicator In Awake Behaving Mice, Vincent Villette, Mariya Chavarha, Ivan K Dimov, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J Schnitzer, Guoqiang Bi, Katalin Toth, Jun Ding, Stéphane Dieudonné, Michael Z Lin

Faculty, Staff and Students Publications

Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the …

Gna11 Brain Somatic Pathogenic Variant In An Individual With Phacomatosis Pigmentovascularis, Joseph M Sliepka, Sarah C Mcgriff, Linda Z Rossetti, Peyman Bizargity, Haley Streff, Yi-Shan Lee, Hongzheng Dai, Satyamaanasa Polubothu, Grace Lee, Vicky Ren, Jill V Hunter, Daniel J Curry, Fernando Scaglia, Adekunle M Adesina, Irfan Ali, Veronica Kinsler, Lindsay C Burrage, Dana Marafi

Faculty, Staff and Students Publications

OBJECTIVE: To describe the findings of histopathology and genotyping studies in affected brain tissue from an individual with phacomatosis pigmentovascularis (PPV).

METHODS: A retrospective chart review of a 2-year 10-month-old male with a clinical diagnosis of PPV cesiomarmorata (or type V) was performed. Clinical features, brain imaging and histopathology findings, and genotyping studies in his affected brain tissue are summarized.

RESULTS: The proband had a clinically severe neurologic phenotype characterized by global developmental delay, generalized hypotonia, and recurrent episodes of cardiac asystole in the setting of status epilepticus. A somatic pathogenic variant in

CONCLUSIONS: The finding of this variant in …

Results Of A Phase 1 Multicentre Investigation Of Dexmedetomidine Bolus And Infusion In Corrective Infant Cardiac Surgery, Athena F Zuppa, Susan C Nicolson, Nicole S Wilder, Juan C Ibla, Erin A Gottlieb, Kristin M Burns, Mario Stylianou, Felicia Trachtenberg, Hua Ni, Tera H Skeen, Dean B Andropoulos

Faculty, Staff and Students Publications

BACKGROUND: Dexmedetomidine (DEX) is increasingly used intraoperatively in infants undergoing cardiac surgery. This phase 1 multicentre study sought to: (i) determine the safety of DEX for cardiac surgery with cardiopulmonary bypass; (ii) determine the pharmacokinetics (PK) of DEX; (iii) create a PK model and dosing for steady-state DEX plasma levels; and (iv) validate the PK model and dosing.

METHODS: We included 122 neonates and infants (0-180 days) with D-transposition of the great arteries, ventricular septal defect, or tetralogy of Fallot. Dose escalation was used to generate NONMEM® PK modelling, and then validation was performed to achieve low (200-300 pg ml …

Structural Basis Of Amino Acid Surveillance By Higher-Order Trna-Mrna Interactions, Shuang Li, Zhaoming Su, Jean Lehmann, Vassiliki Stamatopoulou, Nikoleta Giarimoglou, Frances E Henderson, Lixin Fan, Grigore D Pintilie, Kaiming Zhang, Muyuan Chen, Steven J Ludtke, Yun-Xing Wang, Constantinos Stathopoulos, Wah Chiu, Jinwei Zhang

Faculty, Staff and Students Publications

Amino acid availability in Gram-positive bacteria is monitored by T-box riboswitches. T-boxes directly bind tRNAs, assess their aminoacylation state, and regulate the transcription or translation of downstream genes to maintain nutritional homeostasis. Here, we report cocrystal and cryo-EM structures of Geobacillus kaustophilus and Bacillus subtilis T-box-tRNA complexes, detailing their multivalent, exquisitely selective interactions. The T-box forms a U-shaped molecular vise that clamps the tRNA, captures its 3' end using an elaborate 'discriminator' structure, and interrogates its aminoacylation state using a steric filter fashioned from a wobble base pair. In the absence of aminoacylation, T-boxes clutch tRNAs and form a continuously …

Bipolar Fresh Osteochondral Allograft Transplantation And Joint Reconstruction For Patellar And Trochlear Cartilage Defects, Omid Jalali, Zachary Vredenburgh, John Prodromo, Neilen Benvegnu, George Frederick Rick Hatch

Faculty, Staff and Students Publications

Patellar instability is a debilitating condition, and trauma due to the dislocations may severely damage the articular cartilage of the patellofemoral joint. The lack of healing capacity of cartilage makes treatment of such lesions challenging. In young patients, preservation of native bone and cartilage is a priority, and therefore arthroplasty procedures should be avoided even in relatively larger lesions. Fresh osteochondral allografting has been described for these difficult and complex cases, with recent studies showing promising results. In this surgical technique, we describe the use of bipolar osteochondral allografts of the patella and trochlea and patellofemoral joint reconstruction for large …

Defining The Layers Of A Sensory Cilium With Storm And Cryoelectron Nanoscopy, Michael A Robichaux, Valencia L Potter, Zhixian Zhang, Feng He, Jun Liu, Michael F Schmid, Theodore G Wensel

Faculty, Staff and Students Publications

Primary cilia carry out numerous signaling and sensory functions, and defects in them, "ciliopathies," cause a range of symptoms, including blindness. Understanding of their nanometer-scale ciliary substructures and their disruptions in ciliopathies has been hindered by limitations of conventional microscopic techniques. We have combined cryoelectron tomography, enhanced by subtomogram averaging, with superresolution stochastic optical reconstruction microscopy (STORM) to define subdomains within the light-sensing rod sensory cilium of mouse retinas and reveal previously unknown substructures formed by resident proteins. Domains are demarcated by structural features such as the axoneme and its connections to the ciliary membrane, and are correlated with molecular …

A Proof-Of-Mechanism Study To Test Effects Of The Nmda Receptor Antagonist Lanicemine On Behavioral Sensitization In Individuals With Symptoms Of Ptsd, Marijn Lijffijt, Charles E Green, Nicholas Balderston, Tabish Iqbal, Megan Atkinson, Brittany Vo-Le, Bylinda Vo-Le, Brittany O'Brien, Christian Grillon, Alan C Swann, Sanjay J Mathew

Faculty, Staff and Students Publications

Background: Individuals with post-traumatic stress disorder (PTSD) have a heightened sensitivity to subsequent stressors, addictive drugs, and symptom recurrence, a form of behavioral sensitization. N-methyl-D-aspartate receptors (NMDARs) are involved in the establishment and activation of sensitized behavior.

Objective: We describe a protocol of a randomized placebo-controlled Phase 1b proof-of-mechanism trial to examine target engagement, safety, tolerability, and possible efficacy of the NMDAR antagonist lanicemine in individuals with symptoms of PTSD (Clinician Administered PTSD Scale [CAPS-5] score ≥ 25) and evidence of behavioral sensitization measured as enhanced anxiety-potentiated startle (APS; T-score ≥ 2.8).

Methods: Subjects (n = 24; age range 21–65) …