Digital Commons Network^™

Multisystem Proteinopathy Due To Vcp Mutations: A Review Of Clinical Heterogeneity And Genetic Diagnosis, Gerald Pfeffer, Grace Lee, Carly S Pontifex, Roberto D Fanganiello, Allison Peck, Conrad C Weihl, Virginia Kimonis

2020-Current year OA Pubs

In this work, we review clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase. VCP is crucial to a multitude of cellular functions including protein quality control, stress granule formation and clearance, and genomic integrity functions, among others. Pathogenic mutations in

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. …

Cardiovascular Tropism And Sequelae Of Sars-Cov-2 Infection, Oleksandr Dmytrenko, Kory J Lavine

2020-Current year OA Pubs

The extrapulmonary manifestation of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became apparent early in the ongoing pandemic. It is now recognized that cells of the cardiovascular system are targets of SARS-CoV-2 infection and associated disease pathogenesis. While some details are emerging, much remains to be understood pertaining to the mechanistic basis by which SARS-CoV-2 contributes to acute and chronic manifestations of COVID-19. This knowledge has the potential to improve clinical management for the growing populations of patients impacted by COVID-19. Here, we review the epidemiology and pathophysiology of cardiovascular sequelae of COVID-19 and outline …

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 …

Surprise And Recency In Novelty Detection In The Primate Brain, Kaining Zhang, Ethan S Bromberg-Martin, Fatih Sogukpinar, Kim Kocher, Ilya E Monosov

2020-Current year OA Pubs

Primates and other animals must detect novel objects. However, the neuronal mechanisms of novelty detection remain unclear. Prominent theories propose that visual object novelty is either derived from the computation of recency (how long ago a stimulus was experienced) or is a form of sensory surprise (stimulus unpredictability). Here, we use high-channel electrophysiology in primates to show that in many primate prefrontal, temporal, and subcortical brain areas, object novelty detection is intertwined with the computations of recency and sensory surprise. Also, distinct circuits could be engaged by expected versus unexpected sensory surprise. Finally, we studied neuronal novelty-to-familiarity transformations during learning …

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

Poly(Gr) And Poly(Ga) In Cerebrospinal Fluid As Potential Biomarkers For C9orf72-Als/Ftd, Gopinath Krishnan, Timothy M Miller, Et Al

2020-Current year OA Pubs

GGGGCC repeat expansion in C9ORF72, which can be translated in both sense and antisense directions into five dipeptide repeat (DPR) proteins, including poly(GP), poly(GR), and poly(GA), is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we developed sensitive assays that can detect poly(GA) and poly(GR) in the cerebrospinal fluid (CSF) of patients with C9ORF72 mutations. CSF poly(GA) and poly(GR) levels did not correlate with age at disease onset, disease duration, or rate of decline of ALS Functional Rating Scale, and the average levels of these DPR proteins were similar in symptomatic and pre-symptomatic …

The Plasmodium Falciparum Abc Transporter Abci3 Confers Parasite Strain-Dependent Pleiotropic Antimalarial Drug Resistance, James M Murithi, Eva S Istvan, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Widespread Plasmodium falciparum resistance to first-line antimalarials underscores the vital need to develop compounds with novel modes of action and identify new druggable targets. Here, we profile five compounds that potently inhibit P. falciparum asexual blood stages. Resistance selection studies with three carboxamide-containing compounds, confirmed by gene editing and conditional knockdowns, identify point mutations in the parasite transporter ABCI3 as the primary mediator of resistance. Selection studies with imidazopyridine or quinoline-carboxamide compounds also yield changes in ABCI3, this time through gene amplification. Imidazopyridine mode of action is attributed to inhibition of heme detoxification, as evidenced by cellular accumulation and heme …

Fmrp Regulates Gabaa Receptor Channel Activity To Control Signal Integration In Hippocampal Granule Cells, Pan-Yue Deng, Ajeet Kumar, Valeria Cavalli, Vitaly A Klyachko

2020-Current year OA Pubs

Fragile X syndrome, the most common inherited form of intellectual disability, is caused by loss of fragile X mental retardation protein (FMRP). GABAergic system dysfunction is one of the hallmarks of FXS, yet the underlying mechanisms remain poorly understood. Here, we report that FMRP interacts with GABA

Single-Cell Profiling Of Human Dura And Meningioma Reveals Cellular Meningeal Landscape And Insights Into Meningioma Immune Response, Anthony Z Wang, Jay A Bowman-Kirigin, Rupen Desai, Liang-I Kang, Pujan R Patel, Bhuvic Patel, Saad M Khan, Diane Bender, M Caleb Marlin, Jingxian Liu, Joshua W Osbun, Eric C Leuthardt, Michael R Chicoine, Ralph G Dacey, Gregory J Zipfel, Albert H Kim, David G Denardo, Allegra A Petti, Gavin P Dunn

2020-Current year OA Pubs

BACKGROUND: Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding of the meninges largely stems from the use of pre-clinical models rather than human samples.

METHODS: Single-cell RNA sequencing of seven non-tumor-associated human dura samples and six primary meningioma tumor samples (4 matched and 2 non-matched) was performed. Cell type identities, gene expression profiles, and T cell receptor expression were analyzed. Copy number variant (CNV) analysis was performed to identify putative tumor cells and analyze intratumoral CNV heterogeneity. Immunohistochemistry and imaging mass …

Nasally Delivered Interferon-Λ Protects Mice Against Infection By Sars-Cov-2 Variants Including Omicron, Zhenlu Chong, Courtney E Karl, Peter J Halfmann, Yoshihiro Kawaoka, Emma S Winkler, Shamus P Keeler, Michael J Holtzman, Jinsheng Yu, Michael S Diamond

2020-Current year OA Pubs

Although vaccines and monoclonal antibody countermeasures have reduced the morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, variants with constellations of mutations in the spike gene jeopardize their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution are needed. The host-derived cytokine interferon lambda (IFN-λ) has been proposed as a possible treatment based on studies in human coronavirus 2019 (COVID-19) patients. Here, we show that IFN-λ protects against SARS-CoV-2 B.1.351 (Beta) and B.1.1.529 (Omicron) variants in three strains of conventional and human ACE2 transgenic mice. Prophylaxis or therapy with nasally delivered IFN-λ2 limits …

A Genome-Wide Crispr-Cas9 Knockout Screen Identifies Essential And Growth-Restricting Genes In Human Trophoblast Stem Cells, Chen Dong, Shuhua Fu, Rowan M Karvas, Brian Chew, Laura A Fischer, Xiaoyun Xing, Jessica K Harrison, Pooja Popli, Ramakrishna Kommagani, Ting Wang, Bo Zhang, Thorold W Theunissen

2020-Current year OA Pubs

The recent derivation of human trophoblast stem cells (hTSCs) provides a scalable in vitro model system of human placental development, but the molecular regulators of hTSC identity have not been systematically explored thus far. Here, we utilize a genome-wide CRISPR-Cas9 knockout screen to comprehensively identify essential and growth-restricting genes in hTSCs. By cross-referencing our data to those from similar genetic screens performed in other cell types, as well as gene expression data from early human embryos, we define hTSC-specific and -enriched regulators. These include both well-established and previously uncharacterized trophoblast regulators, such as ARID3A, GATA2, and TEAD1 (essential), and GCM1, …

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 …

Stimulating Tam-Mediated Anti-Tumor Immunity With Mannose-Decorated Nanoparticles In Ovarian Cancer, Evan B Glass, Alyssa A Hoover, Kennady K Bullock, Matthew Z Madden, Bradley I Reinfeld, Whitney Harris, Dominique Parker, Demetra H Hufnagel, Marta A Crispens, Dineo Khabele, W Kimryn Rathmell, Jeffrey C Rathmell, Andrew J Wilson, Todd D Giorgio, Fiona E Yull

2020-Current year OA Pubs

BACKGROUND: Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded …

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 …

Pacing Therapy For Atrioventricular Dromotropathy: A Combined Computational-Experimental-Clinical Study, Floor C W M Salden, Peter R Huntjens, Et Al.

2020-Current year OA Pubs

AIMS: Investigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational-experimental-clinical study.

METHODS AND RESULTS: Computer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy. In a proof-of-principle clinical study, left ventricular (LV) pressure and volume were measured in 22 heart failure (HF) patients (LV ejection fraction <35%) with prolonged PR interval (>230 ms) and narrow or non-left bundle branch block QRS complex. Computer simulations and animal studies in normal hearts showed that restoring of AV-coupling …

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. …

Outcomes Of Diabetic Ketoacidosis In Adults With End-Stage Kidney Disease: Retrospective Study Based On A National Database, Karthik Gangu, Sanket D. Basida, Anitha Vijayan, Sindhu Avula, Aniesh Bobba

Open Access Publications

INTRODUCTION: The prevalence of diabetes mellitus (DM) in the United States has steadily increased over the past few decades. End-stage kidney disease (ESKD) and diabetic ketoacidosis (DKA) are among the most common chronic and acute complications of DM. Guidance on the management of DKA in ESKD is limited by lack of evidence. We investigated the in-hospital outcomes of patients hospitalized for DKA with underlying ESKD. Methods: We carried out a retrospective cohort study and utilized the National Inpatient Sample (NIS) database from 2016 to 2018. International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10 CM) codes were used to identify …

Preoperative And Postoperative Patient-Reported Outcome Measurement Information System Scores In Patients Treated For Benign Versus Malignant Soft Tissue Tumors, Jonathan F. Dalton, Ryan Furdock, Landon Cluts, Bharadwaj Jilakara, Douglas Mcdonald, Ryan Calfee, Cara Cipriano

Open Access Publications

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) assesses multiple aspects of patient well-being but has not been thoroughly studied amongst orthopedic oncology patients.

QUESTIONS/PURPOSES: How do preoperative/early postoperative PROMIS scores compare in patients with benign versus malignant soft tissue tumors (STTs) for (1) physical function, (2) pain interference, and (3) depression? Are the differences clinically relevant? What other patient/tumor factors impact PROMIS?

METHODS: This retrospective cohort study included 314 STT patients who underwent resection of a benign (n = 187) or malignant (n = 127) STT over a period of 4.25 years at a single institution. PROMIS physical function, …

Baseline Microglial Activation Correlates With Brain Amyloidosis And Longitudinal Cognitive Decline In Alzheimer Disease, Qing Wang, Gengsheng Chen, Suzanne E Schindler, Jon Christensen, Nicole S Mckay, Jingxia Liu, Sicheng Wang, Zhexian Sun, Jason Hassenstab, Shaney Flores, Russ Hornbeck, Lisa Cash, Carlos Cruchaga, Anne M Fagan, Zhude Tu, John C Morris, Yong Wang, Tammie L S Benzinger, Et Al

Open Access Publications

BACKGROUND AND OBJECTIVES: This study aims to quantify microglial activation in individuals with Alzheimer disease (AD) using the 18-kDa translocator protein (TSPO) PET imaging in the hippocampus and precuneus, the 2 AD-vulnerable regions, and to evaluate the association of baseline neuroinflammation with amyloidosis, tau, and longitudinal cognitive decline.

METHODS: Twenty-four participants from the Knight Alzheimer Disease Research Center (Knight ADRC) were enrolled and classified into stable cognitively normal, progressor, and symptomatic AD groups based on clinical dementia rating (CDR) at 2 or more clinical assessments. The baseline TSPO radiotracer [11C]PK11195 was used to image microglial activation. Baseline CSF concentrations of …

Characterization Of A Novel Microfilarial Antigen For Diagnosis Of Wuchereria Bancrofti Infections, Sarah E. Greene, Kerstin Fischer, Young-Jun Choi, Kurt C. Curtis, Philip J. Budge, Makedonka Mitreva, Christopher L. King, Peter U. Fischer, Gary J. Weil

Open Access Publications

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi and Brugia timori. The Global Program to Eliminate LF uses mass drug administration (MDA) of anti-filarial drugs that clear microfilariae (Mf) from blood to interrupt transmission by mosquitos. New diagnostic tools are needed to assess the impact of MDA on bancroftian filariasis, because available serologic tests can remain positive after successful treatment.

METHODOLOGY/PRINCIPAL FINDINGS: We identified Wb-bhp-1, which encodes a W. bancrofti homologue of BmR1, the B. malayi protein used in the Brugia Rapid antibody test for brugian filariasis. Wb-bhp-1 has a …

Regulation Of Pdf Receptor Signaling Controlling Daily Locomotor Rhythms In Drosophila, Weihua Li, Jennifer S. Trigg, Paul H. Taghert

Open Access Publications

Each day and in conjunction with ambient daylight conditions, neuropeptide PDF regulates the phase and amplitude of locomotor activity rhythms in Drosophila through its receptor, PDFR, a Family B G protein-coupled receptor (GPCR). We studied the in vivo process by which PDFR signaling turns off, by converting as many as half of the 28 potential sites of phosphorylation in its C terminal tail to a non-phosphorylatable residue (alanine). We report that many such sites are conserved evolutionarily, and their conversion creates a specific behavioral syndrome opposite to loss-of-function phenotypes previously described for pdfr. That syndrome includes increases in the amplitudes …

Bisphenol A Exposure Induces Sensory Processing Deficits In Larval Zebrafish During Neurodevelopment, Courtney Scaramella, Joseph B Alzagatiti, Christopher Creighton, Samandeep Mankatala, Fernando Licea, Gabriel M Winter, Jasmine Emtage, Joseph R Wisnieski, Luis Salazar, Anjum Hussain, Faith M Lee, Asma Mammootty, Niyaza Mammootty, Andrew Aldujaili, Kristine A Runnberg, Daniela Hernandez, Trevor Zimmerman-Thompson, Rikhil Makwana, Julien Rouvere, Zahra Tahmasebi, Gohar Zavradyan, Christopher S Campbell, Meghna Komaranchath, Javier Carmona, Jennifer Trevitt, David Glanzman, Adam C Roberts

2020-Current year OA Pubs

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Functional Analysis Of A Novel De Novo Variant In Ppp5c Associated With Microcephaly, Seizures, And Developmental Delay, Sara M Fielder, Jill A Rosenfeld, Lindsay C Burrage, Lisa Emrick, Seema Lalani, Ruben Attali, Joshua N Bembenek, Hieu Hoang, Dustin Baldridge, Gary A Silverman, Undiagnosed Diseases Network, Tim Schedl, Stephen C Pak

2020-Current year OA Pubs

We describe a proband evaluated through the Undiagnosed Diseases Network (UDN) who presented with microcephaly, developmental delay, and refractory epilepsy with a de novo p.Ala47Thr missense variant in the protein phosphatase gene, PPP5C. This gene has not previously been associated with a Mendelian disease, and based on the population database, gnomAD, the gene has a low tolerance for loss-of-function variants (pLI = 1, o/e = 0.07). We functionally evaluated the PPP5C variant in C. elegans by knocking the variant into the orthologous gene, pph-5, at the corresponding residue, Ala48Thr. We employed assays in three different biological processes where pph-5 was …

Bedside Nurses' Perceptions Of Effective Nurse-Physician Communication In General Medical Units: A Qualitative Study, Hirotaka Kato, Jessica M. Clouser, Preetham Talari, Nikita L. Vundi, Akosua K. Adu, Kishore Karri, Kathy B. Isaacs, Mark V. Williams, Romil Chadha, Jing Li

2020-Current year OA Pubs

Background There is a dearth of research on successful interventions to improve nurse-physician communication (NPC). An important step is identifying what matters to bedside nurses and their perceptions of effective NPC communications and actions. Methods We conducted three focus groups with a total of 19 medical unit nurses across two hospitals in one academic medical center in the United States. Using a convenience sampling strategy, five to eight nurses voluntarily participated in each focus group. The recording was transcribed verbatim and two independent coders performed coding and resolved any discrepancies in codes. Qualitative content analysis was pursued to identify themes …