Digital Commons Network^™

Poglut2/3 Double Knockout In Mice Results In Neonatal Lethality With Reduced Levels Of Fibrillin In Lung Tissues, Sanjiv Neupane, Daniel B Williamson, Robyn A Roth, Carmen M Halabi, Robert S Haltiwanger, Bernadette C Holdener

2020-Current year OA Pubs

Fibrillin microfibrils play a critical role in the formation of elastic fibers, tissue/organ development, and cardiopulmonary function. These microfibrils not only provide structural support and flexibility to tissues, but they also regulate growth factor signaling through a plethora of microfibril-binding proteins in the extracellular space. Mutations in fibrillins are associated with human diseases affecting cardiovascular, pulmonary, skeletal, and ocular systems. Fibrillins consist of up to 47 epidermal growth factor-like repeats, of which more than half are modified by protein O-glucosyltransferase 2 (POGLUT2) and/or POGLUT3. Loss of these modifications reduces secretion of N-terminal fibrillin constructs overexpressed in vitro. Here, we investigated …

A Pilot Study Of Nintedanib In Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer, Christine Auberle, Feng Gao, Mark Sloan, Daniel Morgensztern, Linda Winkler, Jeffrey P. Ward, Siddhartha Devarakonda, Timothy P. Rearden, Ramaswamy Govindan, Saiama N. Waqar

2020-Current year OA Pubs

BACKGROUND: Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in

METHODS: Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss >10% within past 6 months. Nintedanib was …

Python Tooth-Inspired Fixation Device For Enhanced Rotator Cuff Repair, Iden Kurtaliaj, Ethan D Hoppe, Yuxuan Huang, David Ju, Jacob A Sandler, Donghwan Yoon, Guy M Genin

2020-Current year OA Pubs

Rotator cuff repair surgeries fail frequently, with 20 to 94% of the 600,000 repairs performed annually in the United States resulting in retearing of the rotator cuff. The most common cause of failure is sutures tearing through tendons at grasping points. To address this issue, we drew inspiration from the specialized teeth of snakes of the Pythonoidea superfamily, which grasp soft tissues without tearing. To apply this nondamaging gripping approach to the surgical repair of tendon, we developed and optimized a python tooth-inspired device as an adjunct to current rotator cuff suture repair and found that it nearly doubled repair …

Obesity Is Associated With Muscle Atrophy In Rotator Cuff Tear, Simone D Herzberg, Robert H Brophy, Matthew V Smith, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The primary goal of this study is to evaluate the relationship between Body Mass Index (BMI) and muscle atrophy in individuals with rotator cuff tears.

METHODS: This study consists of patients with rotator cuff tears identified by MRI from two independent cohorts, the Rotator Cuff Outcomes Workgroup (ROW) and the Multicenter Orthopaedic Outcomes Network (MOON). Presence of atrophy (yes/no) and severity of atrophy (as an ordinal variable) were assessed on MRI by expert physicians. We used multivariable regression models to evaluate the relationship between BMI and muscle atrophy while adjusting for age and sex in each study, conducted sensitivity …

Real-World And Clinical Trial Outcomes In Large B-Cell Lymphoma With Axicabtagene Ciloleucel Across Race And Ethnicity, Frederick L Locke, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival …

Injury-Induced Foxm1 Expression In The Mouse Kidney Drives Epithelial Proliferation By A Cyclin F-Dependent Mechanism, Megan L. Noonan, Yoshiharu Muto, Yasuhiro Yoshimura, Aidan Leckie-Harre, Haojia Wu, Vladimir V. Kalinichenko, Benjamin D. Humphreys, Monica Chang-Panesso

2020-Current year OA Pubs

Acute kidney injury (AKI) strongly upregulates the transcription factor Foxm1 in the proximal tubule in vivo, and Foxm1 drives epithelial proliferation in vitro. Here, we report that deletion of Foxm1 either with a nephron-specific Cre driver or by inducible global deletion reduced proximal tubule proliferation after ischemic injury in vivo. Foxm1 deletion led to increased AKI to chronic kidney disease transition, with enhanced fibrosis and ongoing tubule injury 6 weeks after injury. We report ERK mediated FOXM1 induction downstream of the EGFR in primary proximal tubule cells. We defined FOXM1 genomic binding sites by cleavage under targets and release using …

The Vaginal Immunoproteome For The Prediction Of Spontaneous Preterm Birth: A Retrospective Longitudinal Study, Zachary Shaffer, Roberto Romero, Adi L Tarca, Jose Galaz, Marcia Arenas-Hernandez, Dereje W Gudicha, Tinnakorn Chaiworapongsa, Eunjung Jung, Manaphat Suksai, Kevin R Theis, Nardhy Gomez-Lopez

2020-Current year OA Pubs

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with intact (spontaneous preterm labor [sPTL]) or ruptured (preterm prelabor rupture of membranes [PPROM]) membranes. The prediction of spontaneous preterm birth (sPTB) remains underpowered due to its syndromic nature and the dearth of independent analyses of the vaginal host immune response. Thus, we conducted the largest longitudinal investigation targeting vaginal immune mediators, referred to herein as the immunoproteome, in a population at high risk for sPTB.

METHODS: Vaginal swabs were collected across gestation from pregnant …

Clinical Prediction For Surgical Versus Nonsurgical Interventions In Patients With Vertebral Osteomyelitis And Discitis, Jennifer Lee, Miguel A. Ruiz-Cardozo, Rujvee P. Patel, Saad Javeed, Raj Swaroop Lavadi, Catherine Newsom-Stewart, Anton Alyakin, Camilo A. Molina, Nitin Agarwal, Wilson Z. Ray, Michele Santacatterina, Brenton H. Pennicooke

2020-Current year OA Pubs

BACKGROUND: Vertebral osteomyelitis and discitis (VOD), an infection of intervertebral discs, often requires spine surgical intervention and timely management to prevent adverse outcomes. Our study aims to develop a machine learning (ML) model to predict the indication for surgical intervention (during the same hospital stay) versus nonsurgical management in patients with VOD.

METHODS: This retrospective study included adult patients (≥18 years) with VOD (ICD-10 diagnosis codes M46.2,3,4,5) treated at a single institution between 01/01/2015 and 12/31/2019. The primary outcome studied was surgery. Candidate predictors were age, sex, race, Elixhauser comorbidity index, first-recorded lab values, first-recorded vital signs, and admit diagnosis. …

Noninvasive Assessment Of The Lung Inflammation-Fibrosis Axis By Targeted Imaging Of Cmklr1, Philip Z Mannes, Taylor S Adams, Samaneh Farsijani, Clayton E Barnes, Joseph D Latoche, Kathryn E Day, Jessie R Nedrow, Farida Ahangari, Naftali Kaminski, Janet S Lee, Sina Tavakoli

2020-Current year OA Pubs

Precision management of fibrotic lung diseases is challenging due to their diverse clinical trajectories and lack of reliable biomarkers for risk stratification and therapeutic monitoring. Here, we validated the accuracy of CMKLR1 as an imaging biomarker of the lung inflammation-fibrosis axis. By analyzing single-cell RNA sequencing datasets, we demonstrated

Harmonized Cross-Species Cell Atlases Of Trigeminal And Dorsal Root Ganglia, Shamsuddin A Bhuiyan, Lite Yang, Lisa A Mcilvried, Bryan A Copits, Zachariah Bertels, John S Del Rosario, Allie J Widman, Richard A Slivicki, Jiwon Yi, Robert W Gereau Iv, Et Al.

2020-Current year OA Pubs

Sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli to the central nervous system. Single-cell RNA sequencing has provided insights into the diversity of sensory ganglia cell types in rodents, nonhuman primates, and humans, but it remains difficult to compare cell types across studies and species. We thus constructed harmonized atlases of the DRG and TG that describe and facilitate comparison of 18 neuronal and 11 non-neuronal cell types across six species and 31 datasets. We then performed single-cell/nucleus RNA sequencing of DRG from both human and the …

Protein Restriction Slows The Development And Progression Of Pathology In A Mouse Model Of Alzheimer's Disease, Reji Babygirija, Natalie M Niemi, Et Al.

2020-Current year OA Pubs

Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer's disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also …

Structural Basis For Hyperpolarization-Dependent Opening Of Human Hcn1 Channel, Verena Burtscher, Jonathan Mount, Jian Huang, John Cowgill, Yongchang Chang, Kathleen Bickel, Jianhan Chen, Peng Yuan, Baron Chanda

2020-Current year OA Pubs

Hyperpolarization and cyclic nucleotide (HCN) activated ion channels are critical for the automaticity of action potentials in pacemaking and rhythmic electrical circuits in the human body. Unlike most voltage-gated ion channels, the HCN and related plant ion channels activate upon membrane hyperpolarization. Although functional studies have identified residues in the interface between the voltage-sensing and pore domain as crucial for inverted electromechanical coupling, the structural mechanisms for this unusual voltage-dependence remain unclear. Here, we present cryo-electron microscopy structures of human HCN1 corresponding to Closed, Open, and a putative Intermediate state. Our structures reveal that the downward motion of the gating …

Incidence And Risk Factors For New And Recurrent Infarcts In Adults With Sickle Cell Disease, Lori C Jordan, Allison A King, Andria L Ford, Taniya E Varughese, Lisa Garrett, Et Al.

2020-Current year OA Pubs

BACKGROUND: Most adults with sickle cell disease will experience a silent cerebral infarction (SCI) or overt stroke. Identifying patient subgroups with increased stroke incidence is important for future clinical trials focused on stroke prevention. Our 3-center prospective cohort study tested the primary hypothesis that adults with sickle cell disease and SCIs have a greater incidence of new stroke or SCI compared with those without SCI. A secondary aim focused on identifying additional risk factors for progressive infarcts, particularly traditional risk factors for stroke in adults.

METHODS AND RESULTS: This observational study included adults with sickle cell disease and no history …

Structural Characterization Of Ligand Binding And Ph-Specific Enzymatic Activity Of Mouse Acidic Mammalian Chitinase, Roberto Efraín Díaz, Andrew K Ecker, Galen J Correy, Pooja Asthana, Iris D Young, Bryan Faust, Michael C Thompson, Ian B Seiple, Steven Van Dyken, Richard M Locksley, James S Fraser

2020-Current year OA Pubs

Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian Chitinase (AMCase), is an enzyme known for its ability to function under acidic conditions in the stomach but is also active in tissues with more neutral pHs, such as the lung. Here, we used a combination of biochemical, structural, and computational modeling approaches to examine how the mouse homolog (mAMCase) can act in both acidic and neutral environments. We measured kinetic properties of mAMCase activity across …

Cancer-Associated Histone H3 N-Terminal Arginine Mutations Disrupt Prc2 Activity And Impair Differentiation, Benjamin A Nacev, Benjamin A Garcia, Et Al.

2020-Current year OA Pubs

Dysregulated epigenetic states are a hallmark of cancer and often arise from genetic alterations in epigenetic regulators. This includes missense mutations in histones, which, together with associated DNA, form nucleosome core particles. However, the oncogenic mechanisms of most histone mutations are unknown. Here, we demonstrate that cancer-associated histone mutations at arginines in the histone H3 N-terminal tail disrupt repressive chromatin domains, alter gene regulation, and dysregulate differentiation. We find that histone H3R2C and R26C mutants reduce transcriptionally repressive H3K27me3. While H3K27me3 depletion in cells expressing these mutants is exclusively observed on the minor fraction of histone tails harboring the mutations, …

A Randomized, Double-Blind, Phase 3 Safety And Efficacy Study Of Ridinilazole Versus Vancomycin For Treatment Of Clostridioides Difficile Infection: Clinical Outcomes With Microbiome And Metabolome Correlates Of Response, Pablo C Okhuysen, Erik R Dubberke, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI.

METHODS: In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), …

Comorbid Neurotrauma Increases Neurodegenerative-Relevant Cognitive, Motor, And Autonomic Dysfunction In Patients With Rapid Eye Movement Sleep Behavior Disorder: A Substudy Of The North American Prodromal Synucleinopathy Consortium, Jonathan E Elliott, Jennifer Mcleland, Yo-El S Ju, Et Al.

2020-Current year OA Pubs

STUDY OBJECTIVES: Rapid eye movement sleep behavior disorder (RBD) is strongly associated with phenoconversion to an overt synucleinopathy, e.g. Parkinson's disease (PD), Lewy body dementia, and related disorders. Comorbid traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD)-henceforth "neurotrauma" (NT)-increase the odds of RBD by ~2.5-fold and are associated with an increased rate of service-connected PD in Veterans. Thus, RBD and NT are both independently associated with PD; however, it is unclear how NT influences neurological function in patients with RBD.

METHODS: Participants ≥18 years with overnight polysomnogram-confirmed RBD were enrolled between 8/2018 to 4/2021 through the North American Prodromal …

Inhibitory Roles Of Apolipoprotein E Christchurch Astrocytes In Curbing Tau Propagation Using Human Pluripotent Stem Cell-Derived Models, Rei Murakami, Hirotaka Watanabe, Hideko Hashimoto, Mayu Kashiwagi-Hakozaki, Tadafumi Hashimoto, Celeste M. Karch, Takeshi Iwatsubo, Hideyuki Okano, Dominantly Inherited Alzheimer Network (Dian)

2020-Current year OA Pubs

Genetic variants in the

Tenovin-1, A Selective Sirt1/2 Inhibitor, Attenuates High-Fat Diet-Induced Hepatic Fibrosis Via Inhibition Of Hsc Activation In Zdf Rats, Swati Sharma, Sreevarsha Gali, Amit Kundu, Jae Hyeon Park, Jae-Sung Kim, Hyung Sik Kim

2020-Current year OA Pubs

Type 2 diabetes mellitus (T2DM) increases the risk of non-alcoholic fatty liver disease (NAFLD) progression to advanced stages, especially upon high-fat diet (HFD). HFD-induced hepatic fibrosis can be marked by oxidative stress, inflammation, and activation of hepatic stellate cells. Sirtuin 1/2 (SIRT1/2), NAD-dependent class III histone deacetylases, are involved in attenuation of fibrosis. In our conducted research, TGF-β1-activated LX-2 cells, free fatty acid (FFA)-treated simultaneous co-culture (SCC) cells, and HFD-induced hepatic fibrosis in Zucker diabetic fatty (ZDF) rats, a widely used animal model in the study of metabolic syndromes, were used to evaluate the protective effect of Tenovin-1, a SIRT1/2 …

Outcomes Of Subsequent Antilymphoma Therapies After Second-Line Axicabtagene Ciloleucel Or Standard Of Care In Zuma-7, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

The optimal management of patients with relapsed/refractory large B-cell lymphoma (LBCL) after disease progression or lack of response to second-line (2L) therapy remains unclear. Here, we report outcomes among patients who received subsequent antilymphoma therapy per investigator discretion separately by their randomized 2L arm in ZUMA-7, namely axicabtagene ciloleucel (axi-cel) vs standard of care (SOC). Progression-free survival (PFS) and overall survival (OS) were calculated from 3L therapy initiation. In the SOC arm, 127 of 179 randomized patients (71%) received 3L therapy. Median PFS among those who received 3L cellular immunotherapy (n = 68) vs those who did not (n = …

Limited Nerve Regeneration Across Acellular Nerve Allografts (Anas) Coincides With Changes In Blood Vessel Morphology And The Development Of A Pro-Inflammatory Microenvironment, Jesús A Acevedo Cintrón, Daniel A Hunter, Lauren Schellhardt, Deng Pan, Susan E Mackinnon, Matthew D Wood

2020-Current year OA Pubs

The use of acellular nerve allografts (ANAs) to reconstruct long nerve gaps (>3 cm) is associated with limited axon regeneration. To understand why ANA length might limit regeneration, we focused on identifying differences in the regenerative and vascular microenvironment that develop within ANAs based on their length. A rat sciatic nerve gap model was repaired with either short (2 cm) or long (4 cm) ANAs, and histomorphometry was used to measure myelinated axon regeneration and blood vessel morphology at various timepoints (2-, 4- and 8-weeks). Both groups demonstrated robust axonal regeneration within the proximal graft region, which continued across …

Relationship Between Sex Biases In Gene Expression And Sex Biases In Autism And Alzheimer's Disease, Stuart B Fass, Bernard Mulvey, Rebecca Chase, Wei Yang, Din Selmanovic, Sneha M Chaturvedi, Eric Tycksen, Lauren A Weiss, Joseph D Dougherty

2020-Current year OA Pubs

BACKGROUND: Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions.

METHODS: In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks.

RESULTS: We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune …

Evaluation Of Copanlisib In Combination With Eribulin In Triple-Negative Breast Cancer Patient-Derived Xenograft Models, Zhanfang Guo, Jingqin Luo, R Jay Mashl, Jeremy Hoog, Piyush Maiti, Nikki Fettig, Sherri R Davies, Rebecca Aft, Jason M Held, Ramaswamy Govindan, Li Ding, Shunqiang Li, Cornelius Von Morze, Kooresh I Shoghi, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

UNLABELLED: The PI3K pathway regulates essential cellular functions and promotes chemotherapy resistance. Activation of PI3K pathway signaling is commonly observed in triple-negative breast cancer (TNBC). However previous studies that combined PI3K pathway inhibitors with taxane regimens have yielded inconsistent results. We therefore set out to examine whether the combination of copanlisib, a clinical grade pan-PI3K inhibitor, and eribulin, an antimitotic chemotherapy approved for taxane-resistant metastatic breast cancer, improves the antitumor effect in TNBC. A panel of eight TNBC patient-derived xenograft (PDX) models was tested for tumor growth response to copanlisib and eribulin, alone or in combination. Treatment-induced signaling changes were …

Phantasus, A Web Application For Visual And Interactive Gene Expression Analysis, Maksim Kleverov, Daria Zenkova, Vladislav Kamenev, Margarita Sablina, Maxim N Artyomov, Alexey A Sergushichev

2020-Current year OA Pubs

Transcriptomic profiling became a standard approach to quantify a cell state, which led to the accumulation of huge amount of public gene expression datasets. However, both reuse of these datasets or analysis of newly generated ones requires significant technical expertise. Here, we present Phantasus: a user-friendly web application for interactive gene expression analysis which provides a streamlined access to more than 96,000 public gene expression datasets, as well as allows analysis of user-uploaded datasets. Phantasus integrates an intuitive and highly interactive JavaScript-based heatmap interface with an ability to run sophisticated R-based analysis methods. Overall Phantasus allows users to go all …

Secure Messaging And Telephone Use For Clinician-To-Clinician Communication, Sunny S Lou, Daphne Lew, Laura R Baratta, Elise Eiden, Christine A Sinsky, Thomas Kannampallil

2020-Current year OA Pubs

No abstract provided.

Hexamerization: Explaining The Original Sin Of Igg-Mediated Complement Activation In Acute Lung Injury, Hrishikesh S. Kulkarni

2020-Current year OA Pubs

Although antibody-mediated lung damage is a major factor in transfusion-related acute lung injury (ALI), autoimmune lung disease (for example, coatomer subunit α [COPA] syndrome), and primary graft dysfunction following lung transplantation, the mechanism by which antigen-antibody complexes activate complement to induce lung damage remains unclear. In this issue of the JCI, Cleary and colleagues utilized several approaches to demonstrate that IgG forms hexamers with MHC class I alloantibodies. This hexamerization served as a key pathophysiological mechanism in alloimmune lung injury models and was mediated through the classical pathway of complement activation. Additionally, the authors provided avenues for exploring therapeutics for …

Shared Vision For Improving Outcomes For Serious Fungal Diseases: Report Of A Patient, Caregiver, And Clinician Summit, Rob Purdie, Lisa A Tushla, Jonathan Ferretti, Gonzalo Kiko Castro, Ricky Watson, Thomas Davis, Brianna Raborg, Patrick B Mazi, Angela Stroman, Carolynn Thomas Jones, Thomas J Walsh, Tom M Chiller, Peter G Pappas, John Meyer, Andrej Spec

2020-Current year OA Pubs

BACKGROUND: Recently, increasing focus on patient input into research and healthcare improvements has fostered expanded patient-centered advocacy efforts. This first pan-fungal disease summit, part of the MYCology Advocacy, Research, & Education effort, brought together patients, caregivers, and mycology experts to better document patient experiences with invasive fungal disease (IFD) and establish priorities for mycology education, advocacy, and research.

METHODS: Patients who had suffered from IFD, their caregivers, clinicians, industry representatives, government officials, and patient advocacy professionals were invited. Patients and caregivers shared their stories and struggles with IFD. Breakout sessions separated mycology experts from patients and caregivers for further discussions …

Mendelian Segregation And High Recombination Rates Facilitate Genetic Analyses In Cryptosporidium Parvum, Abigail Kimball, Lisa Funkhouser-Jones, Wanyi Huang, Rui Xu, William H. Witola, L. David Sibley

2020-Current year OA Pubs

Very little is known about the process of meiosis in the apicomplexan parasite Cryptosporidium despite the essentiality of sex in its life cycle. Most cell lines only support asexual growth of Cryptosporidium parvum (C. parvum), but stem cell derived intestinal epithelial cells grown under air-liquid interface (ALI) conditions support the sexual cycle. To examine chromosomal dynamics during meiosis in C. parvum, we generated two transgenic lines of parasites that were fluorescently tagged with mCherry or GFP on chromosomes 1 or 5, respectively. Infection of ALI cultures or Ifngr1-/- mice with mCherry and GFP parasites resulted in cross-fertilization and the formation …

The First Reported Case Of Treating The Ultra-Central Thorax With Cone Beam Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (Ct-Star), Stephanie Zhao, Robbie Beckert, Xiaodong Zhao, Eric Laugeman, Clifford G. Robinson, Gregory Vlacich, Pamela P. Samson, Joshua P. Schiff

2020-Current year OA Pubs

Stereotactic body radiotherapy (SBRT) to the central and ultra-central thorax is associated with infrequent but potentially serious adverse events. Adaptive SBRT, which provides more precise treatment planning and inter-fraction motion management, may allow the delivery of ablative doses to ultra-central tumors with effective local control and improved toxicity profiles. Herein, we describe the first reported case of cone beam computed tomography (CBCT)-guided stereotactic adaptive radiotherapy (CT-STAR) in the treatment of ultra-central non-small cell lung cancer (NSCLC) in a prospective clinical trial (NCT05785845). An 80-year-old man with radiographically diagnosed early-stage NSCLC presented for definitive management of an enlarging ultra-central lung nodule. …

Subunit Communication Within Dimeric Sf1 Dna Helicases, Binh Nguyen, John Hsieh, Christopher J Fischer, Timothy M Lohman

2020-Current year OA Pubs

Monomers of the Superfamily (SF) 1 helicases, E. coli Rep and UvrD, can translocate directionally along single stranded (ss) DNA, but must be activated to function as helicases. In the absence of accessory factors, helicase activity requires Rep and UvrD homo-dimerization. The ssDNA binding sites of SF1 helicases contain a conserved aromatic amino acid (Trp250 in Rep and Trp256 in UvrD) that stacks with the DNA bases. Here we show that mutation of this Trp to Ala eliminates helicase activity in both Rep and UvrD. Rep(W250A) and UvrD(W256A) can still dimerize, bind DNA, and monomers still retain ATP-dependent ssDNA translocase …