Enhanced Meta-Analysis and Replication Studies Identify Five New
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FLNC Missense Variants in Familial Noncompaction Cardiomyopathy
Cardiogenetics 2019; volume 9:8181 FLNC missense variants than 2 according to current echocardio- in familial noncompaction graphic criteria, or 2.3 on CMR.1,2 Correspondence: Jaap I. van Waning, Approximately 10% of patients diagnosed Department of Clinical Genetics, EE 2038, cardiomyopathy with NCCM have concurrent congenital Erasmus MC, POB 2040, 3000CA Rotterdam, heart defects (CHD).3,4 the Netherlands. Tel.: +3107038388 - Fax: +3107043072. Jaap I. van Waning,1 In 30-40% of cases diagnosed with E-mail: [email protected] Yvonne M. Hoedemaekers,2 NCCM a pathogenic variant can be identi- 2,3 4 Wouter P. te Rijdt, Arne I. Jpma, fied. Around 80% of these pathogenic vari- Acknowledgements: JVW was supported by a Daphne Heijsman,4 Kadir Caliskan,5 ants involve the same sarcomere genes, that grant from the Jaap Schouten Foundation. Elke S. Hoendermis,6 are the major causes for hypertrophic car- WPTR was supported by a Young Talent Program (CVON PREDICT) grant 2017T001 Tineke P. Willems,7 diomyopathy (HCM) and dilated cardiomy- - Dutch Heart Foundation. 8 opathy (DCM), in particular MYH7, Arthur van den Wijngaard, 5,6 3 MYBPC3 and TTN. Filamin C (FLNC) Albert Suurmeijer, Conflict of interest: the authors declare no plays a central role in muscle functioning Marjon A. van Slegtenhorst,1 potential conflict of interest. by maintaining the structural integrity of the Jan D.H. Jongbloed,2 muscle fibers. Pathogenic variants in FLNC Received for publication: 20 March 2019. Danielle F. Majoor-Krakauer,1 2 were found to be associated with a wide Revision received: 29 July 2019. Paul A. -
RNA Sequencing Reveals a Slow to Fast Muscle Fiber Type Transition After Olanzapine Infusion in Rats
RESEARCH ARTICLE RNA Sequencing Reveals a Slow to Fast Muscle Fiber Type Transition after Olanzapine Infusion in Rats Christopher J. Lynch1*, Yuping Xu1, Andras Hajnal2, Anna C. Salzberg3, Yuka Imamura Kawasawa4,5,6 1 Department of Cellular and Molecular Physiology, College of Medicine, Penn State University, Hershey, Pennsylvania, 17033, United States of America, 2 Department of Neural and Behavioral Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, 17033, United States of America, 3 Department a11111 of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, 17033, United States of America, 4 Department of Pharmacology, College of Medicine, Penn State University, Hershey, Pennsylvania, 17033, United States of America, 5 Department of Biochemistry and Molecular Biology, College of Medicine, Penn State University, Hershey, Pennsylvania, 17033, United States of America, 6 The Institute for Personalized Medicine, College of Medicine, Penn State University, Hershey, Pennsylvania, 17033, United States of America * [email protected] OPEN ACCESS Citation: Lynch CJ, Xu Y, Hajnal A, Salzberg AC, Kawasawa YI (2015) RNA Sequencing Reveals a Abstract Slow to Fast Muscle Fiber Type Transition after Olanzapine Infusion in Rats. PLoS ONE 10(4): Second generation antipsychotics (SGAs), like olanzapine, exhibit acute metabolic side ef- e0123966. doi:10.1371/journal.pone.0123966 fects leading to metabolic inflexibility, hyperglycemia, adiposity and diabetes. Understand- Academic Editor: Guillermo López Lluch, ing how SGAs affect the skeletal muscle transcriptome could elucidate approaches for Universidad Pablo de Olavide, Centro Andaluz de mitigating these side effects. Male Sprague-Dawley rats were infused intravenously with ve- Biología del Desarrollo-CSIC, SPAIN hicle or olanzapine for 24h using a dose leading to a mild hyperglycemia. -
Human Regulatory T Cells Mediate Transcriptional Modulation of Dendritic Cell Function
Human Regulatory T Cells Mediate Transcriptional Modulation of Dendritic Cell Function This information is current as Emily Mavin, Lindsay Nicholson, Syed Rafez Ahmed, Fei of September 24, 2021. Gao, Anne Dickinson and Xiao-nong Wang J Immunol published online 28 November 2016 http://www.jimmunol.org/content/early/2016/11/26/jimmun ol.1502487 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2016/11/26/jimmunol.150248 Material 7.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published November 28, 2016, doi:10.4049/jimmunol.1502487 The Journal of Immunology Human Regulatory T Cells Mediate Transcriptional Modulation of Dendritic Cell Function Emily Mavin,*,1 Lindsay Nicholson,*,1 Syed Rafez Ahmed,* Fei Gao,† Anne Dickinson,* and Xiao-nong Wang* Regulatory T cells (Treg) attenuate dendritic cell (DC) maturation and stimulatory function. Current knowledge on the functional impact of semimature DC is limited to CD4+ T cell proliferation and cytokine production. -
Circular RNA Hsa Circ 0005114‑Mir‑142‑3P/Mir‑590‑5P‑ Adenomatous
ONCOLOGY LETTERS 21: 58, 2021 Circular RNA hsa_circ_0005114‑miR‑142‑3p/miR‑590‑5p‑ adenomatous polyposis coli protein axis as a potential target for treatment of glioma BO WEI1*, LE WANG2* and JINGWEI ZHAO1 1Department of Neurosurgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033; 2Department of Ophthalmology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, P.R. China Received September 12, 2019; Accepted October 22, 2020 DOI: 10.3892/ol.2020.12320 Abstract. Glioma is the most common type of brain tumor APC expression with a good overall survival rate. UALCAN and is associated with a high mortality rate. Despite recent analysis using TCGA data of glioblastoma multiforme and the advances in treatment options, the overall prognosis in patients GSE25632 and GSE103229 microarray datasets showed that with glioma remains poor. Studies have suggested that circular hsa‑miR‑142‑3p/hsa‑miR‑590‑5p was upregulated and APC (circ)RNAs serve important roles in the development and was downregulated. Thus, hsa‑miR‑142‑3p/hsa‑miR‑590‑5p‑ progression of glioma and may have potential as therapeutic APC‑related circ/ceRNA axes may be important in glioma, targets. However, the expression profiles of circRNAs and their and hsa_circ_0005114 interacted with both of these miRNAs. functions in glioma have rarely been studied. The present study Functional analysis showed that hsa_circ_0005114 was aimed to screen differentially expressed circRNAs (DECs) involved in insulin secretion, while APC was associated with between glioma and normal brain tissues using sequencing the Wnt signaling pathway. In conclusion, hsa_circ_0005114‑ data collected from the Gene Expression Omnibus database miR‑142‑3p/miR‑590‑5p‑APC ceRNA axes may be potential (GSE86202 and GSE92322 datasets) and explain their mecha‑ targets for the treatment of glioma. -
Single-Cell RNA Sequencing Identifies Senescent Cerebromicrovascular Endothelial Cells in the Aged Mouse Brain
GeroScience (2020) 42:429–444 https://doi.org/10.1007/s11357-020-00177-1 ORIGINAL ARTICLE/UNDERSTANDING SENESCENCE IN BRAIN AGING AND ALZHEIMER’SDISEASE Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain Tamas Kiss & Ádám Nyúl-Tóth & Priya Balasubramanian & Stefano Tarantini & Chetan Ahire & Jordan DelFavero & Andriy Yabluchanskiy & Tamas Csipo & Eszter Farkas & Graham Wiley & Lori Garman & Anna Csiszar & Zoltan Ungvari Received: 31 January 2020 /Accepted: 1 March 2020 /Published online: 31 March 2020 # American Aging Association 2020 Abstract Age-related phenotypic changes of therapeutic exploitation of senolytic drugs in preclinical cerebromicrovascular endothelial cells lead to dysregula- studies. However, difficulties with the detection of senes- tion of cerebral blood flow and blood-brain barrier dis- cent endothelial cells in wild type mouse models of aging ruption, promoting the pathogenesis of vascular cognitive hinder the assessment of the efficiency of senolytic treat- impairment (VCI). In recent years, endothelial cell senes- ments. To detect senescent endothelial cells in the aging cence has emerged as a potential mechanism contributing mouse brain, we analyzed 4233 cells in fractions enriched to microvascular pathologies opening the avenue to the for cerebromicrovascular endothelial cells and other cells Tamas Kiss, Ádám Nyúl-Tóth, Priya Balasubramanian and Stefano Tarantini contributed equally to this work. T. Kiss : Á. Nyúl-Tóth : P. Balasubramanian : S. Tarantini : S. Tarantini : A. Yabluchanskiy : Z. Ungvari C. Ahire : J. DelFavero : A. Yabluchanskiy : T. Csipo : Department of Public Health, International Training Program in A. Csiszar (*) : Z. Ungvari Geroscience, Doctoral School of Basic and Translational Medicine, Department of Biochemistry and Molecular Biology, Reynolds Semmelweis University, Budapest, Hungary Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Vascular Cognitive Impairment and T. -
Genome-Wide DNA Methylation Analysis of KRAS Mutant Cell Lines Ben Yi Tew1,5, Joel K
www.nature.com/scientificreports OPEN Genome-wide DNA methylation analysis of KRAS mutant cell lines Ben Yi Tew1,5, Joel K. Durand2,5, Kirsten L. Bryant2, Tikvah K. Hayes2, Sen Peng3, Nhan L. Tran4, Gerald C. Gooden1, David N. Buckley1, Channing J. Der2, Albert S. Baldwin2 ✉ & Bodour Salhia1 ✉ Oncogenic RAS mutations are associated with DNA methylation changes that alter gene expression to drive cancer. Recent studies suggest that DNA methylation changes may be stochastic in nature, while other groups propose distinct signaling pathways responsible for aberrant methylation. Better understanding of DNA methylation events associated with oncogenic KRAS expression could enhance therapeutic approaches. Here we analyzed the basal CpG methylation of 11 KRAS-mutant and dependent pancreatic cancer cell lines and observed strikingly similar methylation patterns. KRAS knockdown resulted in unique methylation changes with limited overlap between each cell line. In KRAS-mutant Pa16C pancreatic cancer cells, while KRAS knockdown resulted in over 8,000 diferentially methylated (DM) CpGs, treatment with the ERK1/2-selective inhibitor SCH772984 showed less than 40 DM CpGs, suggesting that ERK is not a broadly active driver of KRAS-associated DNA methylation. KRAS G12V overexpression in an isogenic lung model reveals >50,600 DM CpGs compared to non-transformed controls. In lung and pancreatic cells, gene ontology analyses of DM promoters show an enrichment for genes involved in diferentiation and development. Taken all together, KRAS-mediated DNA methylation are stochastic and independent of canonical downstream efector signaling. These epigenetically altered genes associated with KRAS expression could represent potential therapeutic targets in KRAS-driven cancer. Activating KRAS mutations can be found in nearly 25 percent of all cancers1. -
Supplementary Materials
Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine -
Macrophage Activation JUNB Is a Key Transcriptional Modulator Of
JUNB Is a Key Transcriptional Modulator of Macrophage Activation Mary F. Fontana, Alyssa Baccarella, Nidhi Pancholi, Miles A. Pufall, De'Broski R. Herbert and Charles C. Kim This information is current as of October 2, 2021. J Immunol 2015; 194:177-186; Prepublished online 3 December 2014; doi: 10.4049/jimmunol.1401595 http://www.jimmunol.org/content/194/1/177 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2014/12/03/jimmunol.140159 Material 5.DCSupplemental References This article cites 40 articles, 7 of which you can access for free at: http://www.jimmunol.org/content/194/1/177.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 2, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2014 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology JUNB Is a Key Transcriptional Modulator of Macrophage Activation Mary F. Fontana,* Alyssa Baccarella,* Nidhi Pancholi,* Miles A. -
NFKBIZ Antibody Cat
NFKBIZ Antibody Cat. No.: 13-686 NFKBIZ Antibody Immunofluorescence analysis of Raw264.7 cells using NFKBIZ antibody (13-686) at dilution of 1:100. Blue: DAPI for nuclear staining. Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human, Mouse, Rat Recombinant fusion protein containing a sequence corresponding to amino acids 1-220 of IMMUNOGEN: human NFKBIZ (NP_113607.1). TESTED APPLICATIONS: IF, WB WB: ,1:500 - 1:2000 APPLICATIONS: IF: ,1:50 - 1:200 POSITIVE CONTROL: 1) LO2 2) THP-1 September 28, 2021 1 https://www.prosci-inc.com/nfkbiz-antibody-13-686.html 3) Mouse kidney 4) Rat kidney PREDICTED MOLECULAR Observed: 68-90kDa WEIGHT: Properties PURIFICATION: Affinity purification CLONALITY: Polyclonal ISOTYPE: IgG CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: PBS with 0.02% sodium azide, 50% glycerol, pH7.3. STORAGE CONDITIONS: Store at -20˚C. Avoid freeze / thaw cycles. Additional Info OFFICIAL SYMBOL: NFKBIZ IKBZ, INAP, MAIL, NF-kappa-B inhibitor zeta, I-kappa-B-zeta, IL-1 inducible nuclear ankyrin- repeat protein, Ikappa B-zeta variant 3, IkappaB-zeta, ikB-zeta, ikappaBzeta, molecule ALTERNATE NAMES: possessing ankyrin repeats induced by lipopolysaccharide, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta GENE ID: 64332 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References This gene is a member of the ankyrin-repeat family and is induced by lipopolysaccharide (LPS). The C-terminal portion of the encoded product which contains the ankyrin repeats, shares high sequence similarity with the I kappa B family of proteins. The latter are known BACKGROUND: to play a role in inflammatory responses to LPS by their interaction with NF-B proteins through ankyrin-repeat domains. -
Mutations in MYOZ1 As Well As MYOZ2 Encoding the Calsarcins Are Not Associated with Idiopathic and Familial Dilated Cardiomyopathy
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by MDC Repository Repository of the Max Delbrück Center for Molecular Medicine (MDC) Berlin (Germany) http://edoc.mdc-berlin.de/8815/ Mutations in MYOZ1 as well as MYOZ2 encoding the calsarcins are not associated with idiopathic and familial dilated cardiomyopathy Maximilian G. Posch, Andreas Perrot, Rainer Dietz, Cemil Özcelik, Sabine Pankuweit, Volker Ruppert, Anette Richter, and Bernhard Maisch Published in final edited form as: Molecular Genetics and Metabolism. 2007 Jun; 91(2): 207-208 doi: 10.1016/j.ymgme.2007.02.014 Elsevier (The Netherlands) ► Letter to the editor Mutations in MYOZ1 as well as MYOZ2 encoding the calsarcins are not associated with idiopathic and familial dilated cardiomyopathy Maximilian G. Posch, Andreas Perrot, Rainer Dietz, Cemil Özcelik, Sabine Pankuweit, Volker Ruppert, Anette Richter, and Bernhard Maisch 1 Charité – Universitätsmedizin Berlin/Cardiology at Campus Buch & Virchow Klinikum, Helios-Kliniken and Max- Delbrück Center for Molecular Medicine, Wiltbergstrasse 50, 13125 Berlin, Germany 2 Department of Internal Medicine and Cardiology, Philipps University Marburg, Baldingerstrasse, 35043 Marburg, Germany a very weak mRNA expression of MYOZ1 [5]. Conversely, Dear Editor, MYOZ2 encoding calsarcin-1 is predominantly expressed We have read the article of Arola and colleagues [1] with in cardiomyocytes and to lesser extends in skeletal great interest. The authors report a candidate gene muscle [5,6]. Calsarcin-1 is located at the sarcomeric Z- approach in the MYOZ1 gene encoding calsarcin-2 in 185 disk and interacts with DCM disease genes like telethonin patients with idiopathic dilated cardiomyopathy (iDCM). -
Myozenin 1 (MYOZ1) (NM 021245) Human Recombinant Protein Product Data
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TP306448 Myozenin 1 (MYOZ1) (NM_021245) Human Recombinant Protein Product data: Product Type: Recombinant Proteins Description: Recombinant protein of human myozenin 1 (MYOZ1) Species: Human Expression Host: HEK293T Tag: C-Myc/DDK Predicted MW: 31.6 kDa Concentration: >50 ug/mL as determined by microplate BCA method Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Buffer: 25 mM Tris.HCl, pH 7.3, 100 mM glycine, 10% glycerol Preparation: Recombinant protein was captured through anti-DDK affinity column followed by conventional chromatography steps. Storage: Store at -80°C. Stability: Stable for 12 months from the date of receipt of the product under proper storage and handling conditions. Avoid repeated freeze-thaw cycles. RefSeq: NP_067068 Locus ID: 58529 UniProt ID: Q9NP98 RefSeq Size: 1583 Cytogenetics: 10q22.2 RefSeq ORF: 897 Synonyms: CS-2; FATZ; MYOZ Summary: The protein encoded by this gene is primarily expressed in the skeletal muscle, and belongs to the myozenin family. Members of this family function as calcineurin-interacting proteins that help tether calcineurin to the sarcomere of cardiac and skeletal muscle. They play an important role in modulation of calcineurin signaling. [provided by RefSeq, Apr 2012] This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 Myozenin 1 (MYOZ1) (NM_021245) Human Recombinant Protein – TP306448 Product images: Coomassie blue staining of purified MYOZ1 protein (Cat# TP306448). -
Changes in Synaptic Protein Content and Signaling in a Mouse Model of Fragile X Syndrome Kelly Birch University of San Diego
University of San Diego Digital USD Undergraduate Honors Theses Theses and Dissertations Summer 5-22-2016 Changes in Synaptic Protein Content and Signaling in a Mouse Model of Fragile X Syndrome Kelly Birch University of San Diego Peter W. Vanderklish PhD The Scripps Research Institute Follow this and additional works at: https://digital.sandiego.edu/honors_theses Part of the Genetics Commons, and the Molecular and Cellular Neuroscience Commons Digital USD Citation Birch, Kelly and Vanderklish, Peter W. PhD, "Changes in Synaptic Protein Content and Signaling in a Mouse Model of Fragile X Syndrome" (2016). Undergraduate Honors Theses. 20. https://digital.sandiego.edu/honors_theses/20 This Undergraduate Honors Thesis is brought to you for free and open access by the Theses and Dissertations at Digital USD. It has been accepted for inclusion in Undergraduate Honors Theses by an authorized administrator of Digital USD. For more information, please contact [email protected]. Running head: CHANGES IN SYNAPTIC PROTEIN CONTENT 1 Changes in synaptic protein content and signaling in a mouse model of Fragile X Syndrome ______________________ A Thesis Presented to The Faculty and the Honors Program Of the University of San Diego ______________________ By Kelly A. Birch Department of Psychological Sciences 2016 CHANGES IN SYNAPTIC PROTEIN CONTENT 2 Changes in synaptic protein content and signaling in a mouse model of Fragile X Syndrome Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability (ID) in males and a significant cause of ID in females. In addition to ID, affected children may also exhibit hyperactivity, extreme anxiety in multiple forms, poor social communication (including poor eye contact and poor pragmatics), and other autism spectrum behaviors such as restricted interests and repetitive patterns of behavior.