Digital Commons Network^™

The Microbial One-Hit Wonder, Brigida A. Rusconi, Rodney D. Newberry

Open Access Publications

Intestinal inflammation, in the absence of infection, occurs from contributions by genetics and environment. Chen et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210324) challenge this concept by demonstrating that a dominant transmissible dysbiotic microbial community predisposes to intestinal inflammation in absence of genetic alterations.

Large Comparative Analyses Of Primate Body Site Microbiomes Indicate That The Oral Microbiome Is Unique Among All Body Sites And Conserved Among Nonhuman Primates, Abigail E Asangba, Lawrence Mugisha, Joshua Rukundo, Rebecca J Lewis, Ali Halajian, Liliana Cortés-Ortiz, Randall E Junge, Mitchell T Irwin, Johan Karlson, Andrew Perkin, Mrinalini Watsa, Gideon Erkenswick, Karen L Bales, Dorothy L Patton, Anna J Jasinska, Eduardo Fernandez-Duque, Steven R Leigh, Rebecca M Stumpf

Open Access Publications

The study of the mammalian microbiome serves as a critical tool for understanding host-microbial diversity and coevolution and the impact of bacterial communities on host health. While studies of specific microbial systems (e.g., in the human gut) have rapidly increased, large knowledge gaps remain, hindering our understanding of the determinants and levels of variation in microbiomes across multiple body sites and host species. Here, we compare microbiome community compositions from eight distinct body sites among 17 phylogenetically diverse species of nonhuman primates (NHPs), representing the largest comparative study of microbial diversity across primate host species and body sites. Analysis of …

Detection Of Bourbon Virus-Specific Serum Neutralizing Antibodies In Human Serum In Missouri, Usa, Gayan Bamunuarachchi, Houda Harastani, Paul W Rothlauf, Ya-Nan Dai, Ali Ellebedy, Daved Fremont, Sean P J Whelan, David Wang, Adrianus C M Boon

Open Access Publications

Bourbon virus (BRBV) was first discovered in 2014 in a fatal human case. Since then it has been detected in the tick Amblyomma americanum in the states of Missouri and Kansas in the United States. Despite the high prevalence of BRBV in ticks in these states, very few human cases have been reported, and the true infection burden of BRBV in the community is unknown. Here, we developed two virus neutralization assays, a vesicular stomatitis virus (VSV)-BRBV pseudotyped rapid assay and a BRBV focus reduction neutralization assay, to assess the seroprevalence of BRBV neutralizing antibodies in human sera collected in …

Paris And Sparta: Finding The Achilles' Heel Of Sars-Cov-2, Viviana Simon, Ali H Ellebedy, Et Al

Open Access Publications

To understand reinfection rates and correlates of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we established eight different longitudinal cohorts in 2020 under the umbrella of the PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2)/SPARTA (SARS SeroPrevalence And Respiratory Tract Assessment) studies. Here, we describe the PARIS/SPARTA cohorts, the harmonized assays and analysis that are performed across the cohorts, as well as case definitions for SARS-CoV-2 infection and reinfection that have been established by the team of PARIS/SPARTA investigators.

Structure Of A Vaccine-Induced, Germline-Encoded Human Antibody Defines A Neutralizing Epitope On The Sars-Cov-2 Spike N-Terminal Domain, Clara G Altomare, Daniel C Adelsberg, Juan Manuel Carreno, Iden A Sapse, Fatima Amanat, Ali H Ellebedy, Viviana Simon, Florian Krammer, Goran Bajic

Open Access Publications

Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs rational vaccine immunogen design. We isolated a germ line-encoded monoclonal antibody (mAb) from plasmablasts activated upon mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determined its structure in complex with the spike glycoprotein by electron cryomicroscopy (cryo-EM). We show that the mAb engages a previously uncharacterized neutralizing epitope on the spike N-terminal domain (NTD). The high-resolution structure reveals details of the intermolecular interactions and shows that the mAb inserts its heavy …

Invl, An Invasin-Like Adhesin, Is A Type Ii Secretion System Substrate Required For Acinetobacter Baumannii Uropathogenesis, Clay D Jackson-Litteken, Gisela Di Venanzio, Nguyen-Hung Le, Nichollas E Scott, Bardya Djahanschiri, Jesus S Distel, Evan J Pardue, Ingo Ebersberger, Mario F Feldman

Open Access Publications

Acinetobacter baumannii is an opportunistic pathogen of growing concern, as isolates are commonly multidrug resistant. While A. baumannii is most frequently associated with pulmonary infections, a significant proportion of clinical isolates come from urinary sources, highlighting its uropathogenic potential. The type II secretion system (T2SS) of commonly used model Acinetobacter strains is important for virulence in various animal models, but the potential role of the T2SS in urinary tract infection (UTI) remains unknown. Here, we used a catheter-associated UTI (CAUTI) model to demonstrate that a modern urinary isolate, UPAB1, requires the T2SS for full virulence. A proteomic screen to identify …

Isolation Of A Potently Neutralizing And Protective Human Monoclonal Antibody Targeting Yellow Fever Virus, Michael P Doyle, Joseph R Genualdi, Adam L Bailey, Nurgun Kose, Christopher Gainza, Jessica Rodriguez, Kristen M Reeder, Christopher A Nelson, Prashant N Jethva, Rachel E Sutton, Robin G Bombardi, Michael L Gross, Justin G Julander, Daved H Fremont, Michael S Diamond, James E Crowe

Open Access Publications

Yellow fever virus (YFV) causes sporadic outbreaks of infection in South America and sub-Saharan Africa. While live-attenuated yellow fever virus vaccines based on three substrains of 17D are considered some of the most effective vaccines in use, problems with production and distribution have created large populations of unvaccinated, vulnerable individuals in areas of endemicity. To date, specific antiviral therapeutics have not been licensed for human use against YFV or any other related flavivirus. Recent advances in monoclonal antibody (mAb) technology have allowed the identification of numerous candidate therapeutics targeting highly pathogenic viruses, including many flaviviruses. Here, we sought to identify …

The Phenylacetic Acid Catabolic Pathway Regulates Antibiotic And Oxidative Stress Responses In Acinetobacter, Anna J Hooppaw, Jenna C Mcguffey, Gisela Di Venanzio, Juan C Ortiz-Marquez, Brent S Weber, Tasia Joy Lightly, Tim Van Opijnen, Nichollas E Scott, Silvia T Cardona, Mario F Feldman

Open Access Publications

The opportunistic pathogen Acinetobacter baumannii is responsible for a wide range of infections that are becoming increasingly difficult to treat due to extremely high rates of multidrug resistance. Acinetobacter's pathogenic potential is thought to rely on a "persist and resist" strategy that facilitates its remarkable ability to survive under a variety of harsh conditions. The

Cancer Cells Dying From Ferroptosis Impede Dendritic Cell-Mediated Anti-Tumor Immunity, Bartosz Wiernicki, Sophia Maschalidi, Jonathan Pinney, Sandy Adjemian, Tom Vanden Berghe, Kodi S Ravichandran, Peter Vandenabeele

Open Access Publications

Immunogenic cell death significantly contributes to the success of anti-cancer therapies, but immunogenicity of different cell death modalities widely varies. Ferroptosis, a form of cell death that is characterized by iron accumulation and lipid peroxidation, has not yet been fully evaluated from this perspective. Here we present an inducible model of ferroptosis, distinguishing three phases in the process-'initial' associated with lipid peroxidation, 'intermediate' correlated with ATP release and 'terminal' recognized by HMGB1 release and loss of plasma membrane integrity-that serves as tool to study immune cell responses to ferroptotic cancer cells. Co-culturing ferroptotic cancer cells with dendritic cells (DC), reveals …

68ga-Labeled Benzothiazole Derivatives For Imaging Aβ Plaques In Cerebral Amyloid Angiopathy, Truc T Huynh, Yujue Wang, Karna Terpstra, Hong-Jun Cho, Liviu M Mirica, Buck E Rogers

Open Access Publications

Timely diagnostic imaging plays a crucial role in managing cerebral amyloid angiopathy (CAA)-the condition in which amyloid β is deposited on blood vessels. To selectively map these amyloid plaques, we have designed amyloid-targeting ligands that can effectively complex with

Differential And Shared Genetic Effects On Kidney Function Between Diabetic And Non-Diabetic Individuals, Thomas W. Winkler, E Warwick Daw, Mary F. Feitosa, Mary K. Wojczynski, Michael A. Province, Et Al

Open Access Publications

No abstract provided.

A Long-Acting Interleukin-7, Rhil-7-Hyfc, Enhances Car T Cell Expansion, Persistence, And Anti-Tumor Activity, Miriam Y Kim, Reyka Jayasinghe, Jessica M Devenport, Julie K Ritchey, Michael P Rettig, Julie O'Neal, Karl W Staser, Krista M Kennerly, Alun J Carter, Feng Gao, Byung Ha Lee, Matthew L Cooper, John F Dipersio

Open Access Publications

Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free …

Antigen Glycosylation Regulates Efficacy Of Car T Cells Targeting Cd19, Amanda Heard, Jack H Landmann, Ava R Hansen, Yu-Sung Hsu, Mehmet Emrah Selli, John M Warrington, John Lattin, Jufang Chang, Helen Ha, Balraj Doray, Abby M Green, Nathan Singh, Et Al

Open Access Publications

While chimeric antigen receptor (CAR) T cells targeting CD19 can cure a subset of patients with B cell malignancies, most patients treated will not achieve durable remission. Identification of the mechanisms leading to failure is essential to broadening the efficacy of this promising platform. Several studies have demonstrated that disruption of CD19 genes and transcripts can lead to disease relapse after initial response; however, few other tumor-intrinsic drivers of CAR T cell failure have been reported. Here we identify expression of the Golgi-resident intramembrane protease Signal peptide peptidase-like 3 (SPPL3) in malignant B cells as a potent regulator of resistance …

Blimp-1 Molds The Epigenetic Architecture Of Il-21-Mediated Autoimmune Diseases Through An Autoregulatory Circuit, Yu-Wen Liu, Shin-Huei Fu, Ming-Wei Chien, Chao-Yuan Hsu, Ming-Hong Lin, Jia-Ling Dong, Rita Jui-Hsien Lu, Yi-Jing Lee, Pao-Yang Chen, Chih-Hung Wang, Huey-Kang Sytwu

Open Access Publications

Positive regulatory domain 1 (PRDM1) encodes B lymphocyte-induced maturation protein 1 (BLIMP1), also known as a master regulator of T cell homeostasis. We observed a negative relationship between Blimp-1 and IL-21 based on our previous data that Blimp-1 overexpression in T cells suppresses autoimmune diabetes while Blimp-1-deficient T cells contribute to colitis in NOD mice. Reanalysis of published data sets also revealed an inverse correlation between PRDM1 and IL21 in Crohn's disease. Here, we illustrate that Blimp-1 repressed IL-21 by reducing chromatin accessibility and evicting an IL-21 activator, c-Maf, from the Il21 promoter. Moreover, Blimp-1 overexpression-mediated reduction in permissive chromatin …

The Aryl Hydrocarbon Receptor Instructs The Immunomodulatory Profile Of A Subset Of Clec4a4, Wei-Le Wang, Jun Kasamatsu, Satoru Joshita, Susan Gilfillan, Blanda Di Luccia, Santosh K Panda, Do-Hyun Kim, Pritesh Desai, Jennifer K Bando, Stanley Ching-Cheng Huang, Kentaro Yomogida, Steven J Van Dyken, Marina Cella, Marco Colonna, Et Al

Open Access Publications

SignificanceEosinophils contribute to type 2 immunity against helminths and allergens. The small intestine harbors eosinophils with incompletely understood pathophysiological roles. Here, we show that intestinal eosinophils include two subsets. One expresses the inhibitory receptor Clec4a4 and the inhibitory ligand PD-L1 and is unique to the small intestine; the other manifests a proinflammatory phenotype. Both subsets are blood derived. Remarkably, Clec4a4

An Antibody Targeting The N-Terminal Domain Of Sars-Cov-2 Disrupts The Spike Trimer, Naveenchandra Suryadevara, Laura A. Vanblargan, Rita E. Chen, James Brett Case, Michael S. Diamond, Et Al

Open Access Publications

The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope ("supersite") on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRA-Seq), we isolated a large panel of NTD-reactive and SARS-CoV-2-neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, …

Tgf-Β Signaling In Myeloproliferative Neoplasms Contributes To Myelofibrosis Without Disrupting The Hematopoietic Niche, Juo-Chin Yao, Karolyn A. Oetjen, Tianjiao Wang, Haoliang Xu, Grazia Abou-Ezzi, Joseph R. Krambs, Salil Uttarwar, Eric J. Duncavage, Daniel C. Link

Open Access Publications

Myeloproliferative neoplasms (MPNs) are associated with significant alterations in the bone marrow microenvironment that include decreased expression of key niche factors and myelofibrosis. Here, we explored the contribution of TGF-β to these alterations by abrogating TGF-β signaling in bone marrow mesenchymal stromal cells. Loss of TGF-β signaling in Osx-Cre-targeted MSCs prevented the development of myelofibrosis in both MPLW515L and Jak2V617F models of MPNs. In contrast, despite the absence of myelofibrosis, loss of TGF-β signaling in mesenchymal stromal cells did not rescue the defective hematopoietic niche induced by MPLW515L, as evidenced by decreased bone marrow cellularity, hematopoietic stem/progenitor cell number, and …

Peripheral Monocyte-Derived Cells Counter Amyloid Plaque Pathogenesis In A Mouse Model Of Alzheimer's Disease, Ping Yan, Ki-Wook Kim, Qingli Xiao, Xiucui Ma, Leah R. Czerniewski, Haiyan Liu, David R. Rawnsley, Yan Yan, Gwendalyn J. Randolph, Slava Epelman, Jin-Moo Lee, Abhinav Diwan

Open Access Publications

Microglia, the parenchymal tissue macrophages in the brain, surround amyloid plaques in brains of individuals with Alzheimer's disease (AD) but are ineffective at clearing amyloid to mitigate disease progression. Recent studies in mice indicate that microglia are derived exclusively from primitive yolk sac hematopoiesis and self-renew without contribution from ontogenically distinct monocytes/macrophages of definitive adult hematopoietic origin. Using a genetic fate-mapping approach to label cells of definitive hematopoietic origin throughout life span, we discovered that circulating monocytes contribute 6% of plaque-associated macrophages in aged AD mice. Moreover, peripheral monocytes contributed to a higher fraction of macrophages in the choroid plexus, …

Synthetic Gene Circuits For Preventing Disruption Of The Circadian Clock Due To Interleukin-1-Induced Inflammation, Lara Pferdehirt, Anna R Damato, Michal Dudek, Qing-Jun Meng, Erik D Herzog, Farshid Guilak

Open Access Publications

The circadian clock regulates tissue homeostasis through temporal control of tissue-specific clock-controlled genes. In articular cartilage, disruptions in the circadian clock are linked to a procatabolic state. In the presence of inflammation, the cartilage circadian clock is disrupted, which further contributes to the pathogenesis of diseases such as osteoarthritis. Using synthetic biology and tissue engineering, we developed and tested genetically engineered cartilage from murine induced pluripotent stem cells (miPSCs) capable of preserving the circadian clock in the presence of inflammation. We found that circadian rhythms arise following chondrogenic differentiation of miPSCs. Exposure of tissue-engineered cartilage to the inflammatory cytokine interleukin-1 …

Multivalent Designed Proteins Neutralize Sars-Cov-2 Variants Of Concern And Confer Protection Against Infection In Mice, Andrew C Hunt, James Brett Case, Rita E Chen, Baoling Ying, Adam L Bailey, Natasha M Kafai, Michael S Diamond, Et Al

Open Access Publications

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. Consistent with the design model, in the cryo-electron microscopy structure TRI2-2 forms a tripod at the apex of the spike protein that engaged all three receptor binding domains simultaneously. …

Estrogen Metabolites Increase Nociceptor Hyperactivity In A Mouse Model Of Uterine Pain, Zili Xie, Jing Feng, Tao Cai, Ronald Mccarthy, Yuhui Wang, Yonghui Zhao, Zhihua Yi, Kaikai Zang, Yi Yuan, Xueming Hu, Fengxian Li, Qin Liu, Sarah K. England, Hongzhen Hu, Et Al

Open Access Publications

Pain emanating from the female reproductive tract is notoriously difficult to treat, and the prevalence of transient pelvic pain has been placed as high as 70%-80% in women surveyed. Although sex hormones, especially estrogen, are thought to underlie enhanced pain perception in females, the underlying molecular and cellular mechanisms are not completely understood. Here, we showed that the pain-initiating TRPA1 channel was required for pain-related behaviors in a mouse model of estrogen-induced uterine pain in ovariectomized female mice. Surprisingly, 2- and 4-hydroxylated estrogen metabolites (2- and 4-HEMs) in the estrogen hydroxylation pathway, but not estrone, estradiol, or 16-HEMs, directly increased …

Neuronal Hyperexcitability Drives Central And Peripheral Nervous System Tumor Progression In Models Of Neurofibromatosis-1, Corina Anastasaki, Juan Mo, Ji-Kang Chen, Jit Chatterjee, Yuan Pan, Suzanne M Scheaffer, Olivia Cobb, Michelle Monje, Lu Q Le, David H Gutmann

Open Access Publications

Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models of the tumor predisposition syndrome Neurofibromatosis-1 (NF1), with different propensities to develop nervous system cancers. We show that central and peripheral nervous system neurons from mice with tumor-causing Nf1 gene mutations exhibit hyperexcitability and increased secretion of activity-dependent tumor-promoting paracrine factors. We discovered a neurofibroma mitogen (COL1A2) produced by peripheral neurons in an activity-regulated manner, which increases NF1-deficient Schwann cell proliferation, establishing that neurofibromas are regulated by neuronal activity. In contrast, mice with the Arg1809Cys Nf1 mutation, found …

Role Of Nk-Like Cd8+ T Cells During Asymptomatic Borrelia Burgdorferi Infection, Breanna M Scorza, Kurayi G Mahachi, Arin D Cox, Angela J Toepp, Danielle Pessoa-Pereira, Phyllis Tyrrell, Jesse Buch, Jennifer A Foltz, Dean Lee, Christine A Petersen

Open Access Publications

Lyme disease (LD) due to Borrelia burgdorferi is the most prevalent vector-borne disease in the United States. There is a poor understanding of how immunity contributes to bacterial control, pathology, or both during LD. Dogs in an area of endemicity were screened for B. burgdorferi and

Benefits Of Newborn Screening And Hematopoietic Cell Transplant In Infantile Krabbe Disease, Kristin M Page, Margie A Ream, Hemalatha G Rangarajan, Rafael Galindo, Ali Y Mian, Mai-Lan Ho, James Provenzale, Kathryn E Gustafson, Jennifer Rubin, Shalini Shenoy, Joanne Kurtzberg

Open Access Publications

Infantile Krabbe disease (IKD) can be treated with hematopoietic cell transplantation (HCT) if done during the first weeks of life before symptoms develop. To facilitate this, newborn screening (NBS) has been instituted in 8 US states. An application to add IKD to the recommended NBS panel is currently under review. In this report, the outcomes of newborns with IKD diagnosed through NBS and treated with HCT are presented. The unique challenges associated with NBS for this disease are discussed, including opportunities for earlier diagnosis and streamlining treatment referrals. This is a retrospective review of six infants with IKD detected by …

Fluoxetine Exposure Throughout Neurodevelopment Differentially Influences Basilar Dendritic Morphology In The Motor And Prefrontal Cortices, Susan E Maloney, Dora R Tabachnick, Christine Jakes, Selma Avdagic, Amy L Bauernfeind, Joseph D Dougherty

Open Access Publications

The significance of serotonin (5HT) in mental health is underscored by the serotonergic action of many classes of psychiatric medication. 5HT is known to have a significant role in neurodevelopment, thus 5HT disruption during development may have a long term impact on brain structure and circuits. We previously generated a model of 5HT alteration throughout neurodevelopment by maternal administration of the selective serotonin reuptake inhibitor fluoxetine. We found resulting social behavior alterations in the offspring during both postnatal and adult ages. Previous work by others has indicated that early 5HT disruption influences neuronal morphology. Therefore, in the current study we …

Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin

Open Access Publications

Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential …

Oxysterol Compounds In Mouse Mutant Αa- And Αb-Crystallin Lenses Can Improve The Optical Properties Of The Lens, Kehao Wang, Masato Hoshino, Kentaro Uesugi, Naoto Yagi, Barbara K Pierscionek, Usha P Andley

Open Access Publications

Purpose: To investigate how cataract-linked mutations affect the gradient refractive index (GRIN) and lens opacification in mouse lenses and whether there is any effect on the optics of the lens from treatment with an oxysterol compound.

Methods: A total of 35 mice including wild-type and knock-in mutants (Cryaa-R49C and Cryab-R120G) were used in these experiments: 26 mice were treated with topical VP1-001, an oxysterol, in one eye and vehicle in the other, and nine mice were untreated controls. Slit lamp biomicroscopy was used to analyze the lens in live animals and to provide apparent cataract grades. Refractive index in the …

A Novel Methodological Approach To Simultaneously Extract High-Quality Total Rna And Proteins From Cortical And Trabecular Bone, Martina Faraldi, Laura Mangiavini, Caterina Conte, Giuseppe Banfi, Nicola Napoli, Giovanni Lombardi

Open Access Publications

Molecular differences between cortical and trabecular bone, of relevance to understanding the pathophysiological basis of bone diseases, can be determined only through effective isolation methods for RNA and proteins. Here we present a TRIzol-based method, which combines bone pulverization and homogenization to extract simultaneously total RNA and proteins from human cortical and trabecular bone from the same carrot. RNA integrity and purity were determined as the 260/280 nm and 260/230 nm absorbance ratios and the 28S/18S rRNA ratio. Protein integrity and quality were evaluated by Coomassie blue staining. Reverse transcription quantitative polymerase chain reaction and immunoblotting for bone-specific genes and …

Ultrasound-Guided Lumbar Medial Branch Blocks And Intra-Articular Facet Joint Injections: A Systematic Review And Meta-Analysis, Zachary M Ashmore, Michael M Bies, James B Meiling, Rajat N Moman, Leslie C Hassett, Christine L Hunt, Steven P Cohen, W Michael Hooten

Open Access Publications

There is great interest in expanding the use of ultrasound (US), but new challenges exist with its application to lumbar facet-targeted procedures. The primary aim of this systematic review and meta-analysis was to determine the risk of incorrect needle placement associated with US-guided lumbar medial branch blocks (MBB) and facet joint injections (FJI) as confirmed by fluoroscopy or computerized tomography (CT). An a priori protocol was registered, and a database search was conducted. Inclusion criteria included all study types. Risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials and the National Heart, Lung, …

H3k36 Dimethylation Shapes The Epigenetic Interaction Landscape By Directing Repressive Chromatin Modifications In Embryonic Stem Cells, Haifen Chen, Bo Hu, Cynthia Horth, Eric Bareke, Phillip Rosenbaum, Sin Young Kwon, Jacinthe Sirois, Daniel N Weinberg, Faith M Robison, Benjamin A Garcia, Chao Lu, William A Pastor, Jacek Majewski

Open Access Publications

Epigenetic modifications on the chromatin do not occur in isolation. Chromatin-associated proteins and their modification products form a highly interconnected network, and disturbing one component may rearrange the entire system. We see this increasingly clearly in epigenetically dysregulated cancers. It is important to understand the rules governing epigenetic interactions. Here, we use the mouse embryonic stem cell (mESC) model to describe in detail the relationships within the H3K27-H3K36-DNA methylation subnetwork. In particular, we focus on the major epigenetic reorganization caused by deletion of the histone 3 lysine 36 methyltransferase NSD1, which in mESCs deposits nearly all of the intergenic H3K36me2. …