Recent Publications from IDDRC Investigators

Impact of the 2016 US presidential election on OCD symptom presentation: A case illustration. Davis ML, McCann M, Goodman WK, Storch EA. J Clin Psychol. 2018 May;74(5):750-754. doi: 10.1002/jclp.22605. Epub 2018 Mar 12. PMID: 29528496 [PubMed - in process]
Summary: This manuscript details a case illustration of an individual whose symptoms of obsessive-compulsive disorder were directly linked to the election, as well as how these symptoms were addressed via treatment with intensive exposure and response prevention.
Keywords: OCD; election; obsessive-compulsive disorder; stress

Utilization of Mental Health Services by Children Displaced by Hurricane Katrina. Quast T, Gregory S, Storch EA. Psychiatr Serv. 2018 May 1;69(5):580-586. doi: 10.1176/ Epub 2018 Jan 16. PMID: 29334877 [PubMed - in process]
Summary: The contrast between the results for medication utilization and encounters reveals a potential gap in post-Katrina provision of care. Although findings indicate that, on average, displaced children did not experience a disruption in provider visits, the medication estimates suggest that they often did not obtain pharmaceutical treatment. Future disaster responses may be improved by addressing logistical impediments faced by disaster victims in filling their prescriptions for psychiatric medications.
Keywords: childhood trauma; disasters; displacement; Medicaid; utilization patterns

Hormonal, metabolic and skeletal phenotype of Schaaf-Yang syndrome: a comparison to Prader-Willi syndrome. McCarthy JM, McCann-Crosby BM, Rech ME, Yin J, Chen CA, Ali MA, Nguyen HN, Miller JL, Schaaf CP. J Med Genet. 2018 May;55(5):307-315. doi: 10.1136/jmedgenet-2017-105024. Epub 2018 Mar 1. PMID: 29496979 [PubMed - in process]
Summary: This is the first analysis of the hormonal, metabolic and body composition phenotype of Schaaf-Yang Syndrome (SYS). Findings suggest that there is marked but not complete overlap between Prader Willi Syndrome and SYS.
Keywords: MAGEL2 ; IGF-1; bone mineral density; ghrelin; scoliosis

Genotype-phenotype correlations in individuals with pathogenic RERE variants. Jordan VK, Fregeau B, Ge X, Giordano J, Wapner RJ, Balci TB, Carter MT, Bernat JA, Moccia AN, Srivastava A, Martin DM, Bielas SL, Pappas J, Svoboda MD, Rio M, Boddaert N, Cantagrel V, Lewis AM, Scaglia F; Undiagnosed Diseases Network, Kohler JN, Bernstein JA, Dries AM, Rosenfeld JA, DeFilippo C, Thorson W, Yang Y, Sherr EH, Bi W, Scott DA. Hum Mutat. 2018 May;39(5):666-675. doi: 10.1002/humu.23400. Epub 2018 Jan 25. PMID: 29330883 [PubMed - in process] Free PMC Article
Summary: Here, the authors describe nine unrelated individuals with NEDBEH caused by partial deletions or putatively deleterious sequence variants in RERE. An analysis of clinical and molecular data from individuals with NEDBEH suggests the existence of novel genotype–phenotype correlations and demonstrates that a high percentage of RERE pathogenic variants affect a histidine‐rich region in the Atrophin‐1 domain.
Keywords: 1p36 deletion syndrome; CHARGE syndrome; CHD7; NEDBEH; RERE; genotype-phenotype correlations

Myocardial remodeling and susceptibility to ventricular tachycardia in a model of chronic epilepsy. Lai YC, Li N, Lawrence W, Wang S, Levine A, Burchhardt DM, Pautler RG, Valderrábano M, Wehrens XH, Anderson AE. Epilepsia Open. 2018 Mar 23;3(2):213-223. doi: 10.1002/epi4.12107. eCollection 2018 Jun. PMID: 29881800 [PubMed] Free PMC Article
Summary: This paper explores the link between epilepsy and cardiac dysfunction. The authors demonstrate that chronic epilepsy induces changes in myocardial ion channel and adrenergic receptor expression, accompanied by altered cardiac electrophysiology and ventricular excitability.
Keywords: cardiac remodeling; epilepsy; Kv4.2; ventricular tachycardia; β‐adrenergic blockade

Chronic intestinal pseudo-obstruction syndrome and gastrointestinal malrotation in an infant with Schaaf-Yang syndrome - Expanding the phenotypic spectrum. Bayat A, Bayat M, Lozoya R, Schaaf CP. Eur J Med Genet. 2018 Oct;61(10):627-630. doi: 10.1016/j.ejmg.2018.04.007. Epub 2018 Apr 13. PMID: 29660409 [PubMed - in process]
This report highlights a novel patient with phenotypic characteristics of Schaaf-Yang syndrome, and severe chronic digestive malfunction manifesting with both a malrotation and signs of a chronic intestinal pseudo-obstruction.
Keywords: chronic digestive malfunction; chronic intestinal pseudo-obstruction syndrome; MAGEL2; malrotation; Schaaf-Yang syndrome

Politically-focused intrusive thoughts and associated ritualistic behaviors in a community sample. Cepeda SL, McKay D, Schneider SC, La Buissonnière-Ariza V, Egberts JTNE, McIngvale E, Goodman WK, Storch EA. J Anxiety Disord. 2018 May;56:35-42. doi: 10.1016/j.janxdis.2018.03.011. Epub 2018 Mar 31. PMID: 29631796 [PubMed - in process]
Summary: These findings suggest that politically-focused intrusive thoughts and ritualistic behaviors are associated with psychopathology domains in a manner comparable to general obsessive-compulsive symptoms.
Keywords: anxiety; impairment; obsessive-compulsive disorder; politics; social media

Combination anti-Aβ treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice. Chiang ACA, Fowler SW, Savjani RR, Hilsenbeck SG, Wallace CE, Cirrito JR, Das P, Jankowsky JL. J Exp Med. 2018 May 7;215(5):1349-1364. doi: 10.1084/jem.20171484. Epub 2018 Apr 6. PMID: 29626114 [PubMed - in process]
Summary: Here, the authors show that combination therapy of passive anti-AB immunization and chemogenetic arrest of AB production reversed cognitive decline in a mouse model of Alzheimer’s disease, unlike mice receiving either single treatment. Mice receiving the combination therapy also showed resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of mTOR signaling, indicating that combination therapy for Alzheimer’s disease may be an important therapeutic route to explore.
Keywords: mTOR; Alzheimer’s disease; amyloid β; drug development; transgenic mouse

Axon initial segments: structure, function, and disease. Huang CY, Rasband MN. Ann N Y Acad Sci. 2018 May;1420(1):46-61. doi: 10.1111/nyas.13718. Epub 2018 May 11. Review. PMID: 29749636 [PubMed - in process]
Summary: In this review, the authors provide an overview of the axon initial segment (AIS) cytoarchitecture, mechanism of assembly, and recent studies revealing mechanisms of differential transport at the AIS that maintains axon and dendrite identities. They further discuss how genetic mutations in AIS components (i.e., ankyrins, ion channels, and spectrins) and injuries may cause neurological disorders.
Keywords: axon initial segment; cytoskeleton; axon; ankyrin; ion channel; spectrin

Neuroimaging findings of extensive sphenoethmoidal dysplasia in NF1. Tam A, Sliepka JM, Bellur S, Bray CD, Lincoln CM, Nagamani SCS. Clin Imaging. 2018 Sep - Oct;51:160-163. doi: 10.1016/j.clinimag.2018.04.017. Epub 2018 May 16. PMID: 29787982 [PubMed - in process]
Summary: This case report describes a 20-year-old male with neurofibromatosis 1 (NF1) which an extensive cranial bone dysplasia, though he did not show subsequent symptoms or complications. The authors then review the current knowledge of the pathogenesis and management of cranial bone dysplasia in NF1.
Keywords: neurofibromatosis type 1; sphenoethmoidal defect; sphenoid wing dysplasia

The complex relationship between TFEB transcription factor phosphorylation and subcellular localization. Puertollano R, Ferguson SM, Brugarolas J, Ballabio A. EMBO J. 2018 Jun 1;37(11). pii: e98804. doi: 10.15252/embj.201798804. Epub 2018 May 15. Review. PMID: 29764979 [PubMed - in process]
Summary: This reviews the evidence that the MiT-TFE family of transcription is regulated by phosphorylation at multiple key sites. Elucidation of such regulatory mechanisms is of fundamental importance to understand how these transcription factors contribute to both health and disease.
Keywords: TFEB; autophagy; lysosome; mTOR; nucleo‐cytoplasmic shuttling

SRC-3 Coactivator Governs Dynamic Estrogen-Induced Chromatin Looping Interactions during Transcription. Panigrahi AK, Foulds CE, Lanz RB, Hamilton RA, Yi P, Lonard DM, Tsai MJ, Tsai SY, O'Malley BW. Mol Cell. 2018 May 17;70(4):679-694.e7. doi: 10.1016/j.molcel.2018.04.014.PMID: 29775582 [PubMed - in process]
Summary: Data shown here suggest that the enhancer and promoter remain "poised" for transcription via their contacts with GBS1 and GBS2. Upon estradiol-(E2) induction, GBS1 and GBS2 disengage from the enhancer, allowing direct EPC for active transcription.
Keywords: ERα; SRC-3; eRNA; enhancer-promoter interaction; estrogen receptor-α; estrogen-induced transcription; looping determinant; steroid receptor coactivator-3

mTORC2, but not mTORC1, is required for hippocampal mGluR-LTD and associated behaviors. Zhu PJ, Chen CJ, Mays J, Stoica L, Costa-Mattioli M.Nat Neurosci. 2018 Jun;21(6):799-802. doi: 10.1038/s41593-018-0156-7. Epub 2018 May 21.PMID: 29786082 [PubMed - in process]
Summary: Previous reports indicated that mTORC1 was necessary for mGluR-LTD. However, this report shows that while mTORC2 is indeed a major regulator of mGluR-LTD, mTORC1 is not necessary.
Keywords: rapamycin; mTORC1; mTROC2; behavior; metabotropic glutamate receptor (mGluR); long-term depression (LTD); mGLuR-LTD

Using Drosophila to study mechanisms of hereditary hearing loss. Li T, Bellen HJ, Groves AK. Dis Model Mech. 2018 May 31;11(6). pii: dmm031492. doi: 10.1242/dmm.031492. Review. PMID: 29853544 [PubMed - in process] Free PMC Article
Summary: This article discusses the molecular and cellular similarities of the hearing organ in vertebrates (the cochlea) and Drosophila (Johnston’s organ).
Keywords: cochlea; deafness; Drosophila; hair cells; hearing; Usher syndrome

Multimodal Residential Treatment for Adolescent Anxiety: Outcome and Associations with Pre-treatment Variables. Schneider SC, La Buissonnière-Ariza V, Højgaard DRMA, Kay BS, Riemann BC, Eken SC, Lake P, Nadeau JM, Storch EA. Child Psychiatry Hum Dev. 2018 Jun;49(3):434-442. doi: 10.1007/s10578-017-0762-8. PMID: 28988322 [PubMed - in process]
Summary: This study aimed to determine the effect of a multimodal residential treatment program for severe adolescent anxiety, and examine whether treatment outcome was associated with pre-treatment anxiety, comorbid disorders, or participant age or gender.  Results indicated a strong effect of the intervention on symptoms of anxiety, depression, and anxiety-related life interference. Most pre-treatment variables were not associated with treatment outcome. However, higher adolescent-reported pre-treatment anxiety was associated with a greater reduction in anxiety at post-treatment, and the presence of a comorbid anxiety disorder was associated with poorer odds of treatment response.
Keywords: adolescent; anxiety; cognitive-behavioral therapy; predictor; residential treatment

The Citrulline Recycling Pathway Sustains Cardiovascular Function in Arginine-Depleted Healthy Mice, but Cannot Sustain Nitric Oxide Production during Endotoxin Challenge. Yuan Y, Mohammad MA, Betancourt A, Didelija IC, Yallampalli C, Marini JC. J Nutr. 2018 Jun 1;148(6):844-850. doi: 10.1093/jn/nxy065. PMID: 29878271 [PubMed - in process]
Summary: Here, the authors show that pegylated arginine deiminase (ADI-PEG20) can deplete circulating arginine without impacting cardiac function in healthy mice but limits nitric oxide (NO) production after endotoxin challenge. Therefore, the citrulline recycling pathway can sustain local arginine availability independently from circulating arginine, satisfying the demand of arginine for endothelial NO production; however, it is unable to do so when a high demand for arginine is elicited by endotoxin.
Keywords: citrulline; endotoxin challenge; mouse; cardiovascular function; arginine; nitric oxide

Tau Activates Transposable Elements in Alzheimer's Disease. Guo C, Jeong HH, Hsieh YC, Klein HU, Bennett DA, De Jager PL, Liu Z, Shulman JM. Cell Rep. 2018 Jun 5;23(10):2874-2880. doi: 10.1016/j.celrep.2018.05.004. PMID: 29874575 [PubMed - in process] Free Article
Summary: Using RNA sequencing from 636 human brains and Drosophila transgenic models, the authors show that transposable element (TE) activation differs in the brains of individuals with Alzheimer’s disease and demonstrate that tau is sufficient to activate numerous TEs.
Keywords: Alu; Alzheimer's disease; ERV; LINE1; MAPT; RNA sequencing; chromatin; genomic instability; neurodegeneration; retrotransposon

βIV Spectrinopathies Cause Profound Intellectual Disability, Congenital Hypotonia, and Motor Axonal Neuropathy. Wang CC, Ortiz-González XR, Yum SW, Gill SM, White A, Kelter E, Seaver LH, Lee S, Wiley G, Gaffney PM, Wierenga KJ, Rasband MN. Am J Hum Genet. 2018 Jun 7;102(6):1158-1168. doi: 10.1016/j.ajhg.2018.04.012. Epub 2018 May 31. PMID: 29861105 [PubMed - in process]
Summary: Previously unreported mutations in the SPTBN4 gene were identified in six patients presenting with congenital hypotonia, intellectual disability, and motor axonal and auditory neuropathy. The authors then used neuronal cell cultures to show that the variants seen in humans disrupt the localization of BIV spectrin to the axon initial segment (AIS). Mouse modeling further reveals that this loss can only partially be compensated for by similar proteins.
Keywords: axon initial segment; cytoskeleton; node of Ranvier

Depleting Trim28 in adult mice is well tolerated and reduces levels of α-synuclein and tau. Rousseaux MW, Revelli JP, Vázquez-Vélez GE, Kim JY, Craigen E, Gonzales K, Beckinghausen J, Zoghbi HY.Elife. 2018 Jun 4;7. pii: e36768. doi: 10.7554/eLife.36768.PMID: 29863470 [PubMed - in process] Free PMC Article
Summary: Building on previous findings that TRIM28 regulates α-Syn and Tau, the authors show that genetic suppression of Trim28 in adult mice does not cause behavioral or pathological phenotypes and results in a decrease of α-Syn and tau levels. α-Syn and Tau are disease-driving proteins, so deletion of TRIM28 may represent a new therapeutic target for disease pathology.
Keywords: Alzheimer's disease; Parkinson's disease; tau; alpha-synuclein; dosage sensitivity; human; mouse; neuroscience; safety

Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain. Lin G, Lee PT, Chen K, Mao D, Tan KL, Zuo Z, Lin WW, Wang L, Bellen HJ. Cell Metab. 2018 Jun 7. pii: S1550-4131(18)30326-7. doi: 10.1016/j.cmet.2018.05.019. [Epub ahead of print] PMID: 29909971 [PubMed - as supplied by publisher]
Summary: In humans, mutations in the gene PLA2G6 can cause a number of diseases, collectively known as PLA2G6-associated neurodegeneration (PLAN). This study furthers our understanding of iPLA2 by exploring its previously unrecognized role in sphingolipid homeostasis and endolysosomal function.
Keywords: Parkinson's disease; ceramide phosphatidylethanolamine; complex I; endosome; infantile neuroaxonal dystrophy (INAD); lysosomal storage disease; lysosome; mitochondria; neurodegeneration with brain iron accumulation; sphingomyelin

Gene therapy for repair and regeneration of bone and cartilage. Grol MW, Lee BH. Curr Opin Pharmacol. 2018 Jun;40:59-66. doi: 10.1016/j.coph.2018.03.005. Epub 2018 Apr 2. Review. PMID: 29621661 [PubMed - in process]
Summary: In this review, the authors provide an overview of viral gene therapies being developed for treatment of bone and cartilage pathologies, with an emphasis on emerging combinatorial strategies as well as those targeting intracellular mediators such as miRNAs.
Keywords: miRNA, gene therapy, regeneration, bone repair, regeneration

The role of FREM2 and FRAS1 in the development of congenital diaphragmatic hernia. Jordan VK, Beck TF, Hernandez-Garcia A, Kundert PN, Kim BJ, Jhangiani SN, Gambin T, Starkovich M, Punetha J, Paine IS, Posey JE, Li AH, Muzny D, Hsu CW, Lashua AJ, Sun X, Fernandes CJ, Dickinson ME, Lally KP, Gibbs RA, Boerwinkle E, Lupski JR, Scott DA. Hum Mol Genet. 2018 Jun 15;27(12):2064-2075. doi: 10.1093/hmg/ddy110. PMID: 29618029 [PubMed - in process]
Summary: This study shows that deficiency of FREM2, and possibly FRAS1, are associated with an increased risk of developing CDH and that loss of the FREM1/FREM2/FRAS1 complex, or its function, leads to anterior sac CDH development through its effects on mesothelial fold progression.
Keywords: congenital diaphragmatic hernia; recessive; mutation; mesothelial fold; Fraser syndrome; genetic disorder; FREM2; FRAS1

Genome-wide distribution of linker histone H1.0 is independent of MeCP2. Ito-Ishida A, Yamalanchili HK, Shao Y, Baker SA, Heckman LD, Lavery LA, Kim JY, Lombardi LM, Sun Y, Liu Z, Zoghbi HY.Nat Neurosci. 2018 Jun;21(6):794-798. doi: 10.1038/s41593-018-0155-8. Epub 2018 May 25.PMID: 29802390 [PubMed - in process]
Summary: Previous reports have suggested that MeCP2 competes with linker histone H1, but this study shows that H1.0 binding was not changed upon MeCP2 depletion. Further, overexpression of H1.0 did not alter MeCP2 binding. Together, these results suggest the functional binding of MeCP2 and H1.0 are largely independent.
Keywords: MeCP2; histone; Rett syndrome; ChIP-seq

Genetic strategies to tackle neurological diseases in fruit flies. Şentürk M, Bellen HJ. Curr Opin Neurobiol. 2018 Jun;50:24-32. doi: 10.1016/j.conb.2017.10.017. Epub 2017 Nov 9. Review. PMID: 29128849 [PubMed - in process]
Summary: This review highlights how systematic and combinatorial approached bases on recently established methods provide us with integrated tool sets that can be applied to the study of neurodevelopmental and neurodegenerative disorders.
Keywords: genetic tools; neurodevelopmental disorders; neurodegenerative disorders; Drosophila; disease-associated genes

Cardiomyocyte Proliferation for Therapeutic Regeneration. Leach JP, Martin JF. Curr Cardiol Rep. 2018 Jun 14;20(8):63. doi: 10.1007/s11886-018-1011-x. Review. PMID: 29904823 [PubMed - in process]
Summary: This review discusses progress made toward the regeneration of cardiac tissue in the mammalian heart through the stimulation of mature cardiomyocyte renewal.
Keywords: cardiomyocyte; cardiovascular disease; cell cycle; heart failure; proliferation; regeneration

Unveiling "Musica Universalis" of the Cell: A Brief History of Biological 12-Hour Rhythms. Zhu B, Dacso CC, O'Malley BW. J Endocr Soc. 2018 Jun 6;2(7):727-752. doi: 10.1210/js.2018-00113. eCollection 2018 Jul 1. Review. PMID: 29978151 [PubMed] Free PMC Article
Summary: In this article, the authors review the current literature to propose a model where combined actions of both the circadian and 12-hour clock are required to ensure cellular homeostasis and promote organism integrity and overall fitness.
Keywords: 12h-clock; aging; chronotherapy; ER stress; mitochondria; NAFLD; Xbp1

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study. Jain M, Tam A, Shapiro JR, Steiner RD, Smith PA, Bober MB, Hart T, Cuthbertson D, Krischer J, Mullins M, Bellur S, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Lee B, Sutton VR; , Members of the Brittle Bone Disorders Consortium*,, Nagamani SCS. Genet Med. 2018 Jul 4. doi: 10.1038/s41436-018-0045-1. [Epub ahead of print] PMID: 29970925 [PubMed - as supplied by publisher]
Summary: From the largest cohort of individuals with Osteogenesis imperfect (OI), the authors provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves.
Keywords: growth; height; natural history study; osteogenesis imperfecta; weight

Presentation and Correlates of Hoarding Behaviors in Children with Autism Spectrum Disorders and Comorbid Anxiety or Obsessive-Compulsive Symptoms. La Buissonnière-Ariza V, Wood JJ, Kendall PC, McBride NM, Cepeda SL, Small BJ, Lewin AB, Kerns C, Storch EA. J Autism Dev Disord. 2018 Jul 4. doi: 10.1007/s10803-018-3645-3. [Epub ahead of print]PMID: 29974314 [PubMed - as supplied by publisher]
Summary: In 204 children aged 7-13 with autism spectrum disorder (ASD) and comorbid anxiety or obsessive-compulsive disorder symptoms, 34 percent were found to have at least moderate levels of hoarding, with 7 percent presenting with extreme levels of hoarding. Additional risk factors found include gender, increased social difficulties, and comorbid psychiatric symptom severity.
Keywords: ASD; anxiety; autism; hoarding; OCD; pediatric; prevalence

Glial βII Spectrin Contributes to Paranode Formation and Maintenance. Susuki K, Zollinger DR, Chang KJ, Zhang C, Huang CY, Tsai CR, Galiano MR, Liu Y, Benusa SD, Yermakov LM, Griggs RB, Dupree JL, Rasband MN. J Neurosci. 2018 Jul 4;38(27):6063-6075. doi: 10.1523/JNEUROSCI.3647-17.2018. Epub 2018 May 31. PMID: 29853631 [PubMed - in process]
Summary: Myelinating glia cells form paranodal axoglial junctions to help ensure proper formation of nodes of Ranvier. Knockout of βII spectrin in myelinating glial cells disrupted the paranodal cell adhesion complex in both the peripheral and central nervous systems, resulting to muscle weakness and sciatic nerve conduction slowing in juvenile and middle-aged mice.
Keywords: myelin; node of Ranvier; paranode; spectrin

Loss of Atoh1 from neurons regulating hypoxic and hypercapnic chemoresponses causes neonatal respiratory failure in mice. van der Heijden ME, Zoghbi HY. Elife. 2018 Jul 4;7. pii: e38455. doi: 10.7554/eLife.38455. PMID: 29972353 [PubMed - in process] Free PMC Article
Summary: This study answers the decades-old question about the cause of respiratory failure in Atoh1-null mice: they die of an inability to modulate respiratory rhythms in response to hypoxic and hypercapnic conditions.
Keywords: Atoh1; apnea; developmental biology; hypercapnia; hypoxia; mouse; neuroscience; respiration; respiratory chemoresponses

A randomized trial to study the comparative efficacy of phenylbutyrate and benzoate on nitrogen excretion and ureagenesis in healthy volunteers. Nagamani SCS, Agarwal U, Tam A, Azamian M, McMeans A, Didelija IC, Mohammad MA, Marini JC.Genet Med. 2018 Jul;20(7):708-716. doi: 10.1038/gim.2017.167. Epub 2017 Oct 12.PMID: 29693650 [PubMed - in process] Free PMC Article
Summary: In this study, the authors demonstrate that phenylbutyrate was more efficacious than benzoate at conjugating and disposing of nitrogen. The inclusion of both drugs resulted in a reduction of treatment cost without compromising the amount of nitrogen conjugated.
Keywords: randomized trial; ureagenesis; nitrogen excretion; phenylbutyrate; benzoate

Attentional fluctuations induce shared variability in macaque primary visual cortex. Denfield GH, Ecker AS, Shinn TJ, Bethge M, Tolias AS.Nat Commun. 2018 Jul 9;9(1):2654. doi: 10.1038/s41467-018-05123-6.PMID: 29985411 Free PMC Article
Summary: This study helps to explain the variability in neuronal responses to visual stimuli as a function of internal states, such as attention, rather than noise.
Keywords:  attention; visual cortex; noise correlation; change detection task

Concurrent cell type-specific isolation and profiling of mouse brains in inflammation and Alzheimer's disease. Swartzlander DB, Propson NE, Roy ER, Saito T, Saido T, Wang B, Zheng H.JCI Insight. 2018 Jul 12;3(13). pii: 121109. doi: 10.1172/jci.insight.121109. [Epub ahead of print]PMID: 29997299 [PubMed - as supplied by publisher] Free PMC Article
Summary: The authors describe here the development of a concurrent brain cell type acquisition (CoBrA) methodology, enabling the isolation and profiling of microglia, astrocytes, endothelia, and oligodendrocytes from a single adult mouse forebrain. CoBrA methodology can be readily implemented to interrogate multiple CNS cell types in any mouse model at any age.
Keywords: Alzheimer’s disease; expression profiling; inflammation; neurodegeneration; neuroscience

Olfactory reference syndrome symptoms in Chinese university students: Phenomenology, associated impairment, and clinical correlates. Zhou X, Schneider SC, Cepeda SL, Storch EA .Compr Psychiatry. 2018 Oct;86:91-95. doi: 10.1016/j.comppsych.2018.06.013. Epub 2018 Jul 17. PMID: 30086511 [PubMed - in process]
Summary: These findings suggest that olfactory reference syndrome (ORS) symptoms are relatively distinct from other disorders in a non-clinical sample. Future studies are encouraged to further explore the phenomenology, etiology, neurobiology, and treatment of ORS in order to inform diagnosis and nosology.
Keywords: olfactory reference syndrome; ORS; severity; student; self-report; OCD

Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency. Lotfi P, Tse DY, Di Ronza A, Seymour ML, Martano G, Cooper JD, Pereira FA, Passafaro M, Wu SM, Sardiello M. Autophagy. 2018;14(8):1419-1434. doi: 10.1080/15548627.2018.1474313. Epub 2018 Jul 23. PMID: 29916295 [PubMed - in process] Free PMC Article
Summary: Small-molecule-induced autophagy enhancement can improve the neurological symptoms associated with a lysosomal enzyme deficiency and could provide a viable therapeutic approach to neuropathic lysosomal storage diseases.
Keywords: autophagic vacuoles; ERG; MPS IIIB; Sanfilippo syndrome; TFEB; autophagy; lysosomal storage diseases; mucopolysaccharidosis type IIIB; retina; trehalose

High-Throughput Functional Analysis Distinguishes Pathogenic, Nonpathogenic, and Compensatory Transcriptional Changes in Neurodegeneration. Al-Ramahi I, Lu B, Di Paola S, Pang K, de Haro M, Peluso I, Gallego-Flores T, Malik NT, Erikson K, Bleiberg BA, Avalos M, Fan G, Rivers LE, Laitman AM, Diaz-García JR, Hild M, Palacino J, Liu Z, Medina DL, Botas J. Cell Syst. 2018 Jul 25;7(1):28-40.e4. doi: 10.1016/j.cels.2018.05.010. Epub 2018 Jun 20. PMID: 29936182 [PubMed - in process]
Summary: Using high-throughput behavioral testing in Drosophila, the authors tested 312 genes whose expression is dysregulated both in patients with Huntington Disease (HD) and HD mice. They found that transcriptional changes in synaptic biology and calcium signaling are compensatory whereas alterations involving the actin cytoskeleton and inflammation drive disease. The approach used here can be applied to other transcriptomics datasets to help identify therapeutic entry points.
Keywords: neurodegenerative diseases; Huntington disease, Drosophila; high-throughput behavioral testing; transcriptional changes; actin; cytoskeleton; inflammation; macroautophagy; transcriptomics; calcium signaling

Therapeutic alliance in youth with autism spectrum disorder receiving cognitive-behavioral treatment for anxiety. Kerns CM, Collier A, Lewin AB, Storch EA. Autism. 2018 Jul;22(5):636-640. doi: 10.1177/1362361316685556. Epub 2017 May 17. PMID: 28514865 [PubMed - in process]
Summary: Symptoms of autism spectrum disorder may influence alliance in psychotherapy. This study examined therapeutic alliance and its relationship with child characteristics and anxiety treatment outcomes in youth with autism spectrum disorder. Ratings of alliance were commensurate to ratings seen in children without autism spectrum disorder. Measures of treatment outcome, but not pre-treatment characteristics, were significantly associated with therapist ratings of alliance strength. Data suggest that therapeutic alliance may not be impaired in anxious youth with autism spectrum disorder and may be associated with treatment outcome.
Keywords: anxiety; autism spectrum disorder; cognitive-behavioral therapy; therapeutic alliance

Functional variants in TBX2 are associated with a syndromic cardiovascular and skeletal developmental disorder. Liu N, Schoch K, Luo X, Pena LDM, Bhavana VH, Kukolich MK, Stringer S, Powis Z, Radtke K, Mroske C, Deak KL, McDonald MT, McConkie-Rosell A, Markert ML, Kranz PG, Stong N, Need AC, Bick D, Amaral MD, Worthey EA, Levy S; Undiagnosed Diseases Network (UDN), Wangler MF, Bellen HJ, Shashi V, Yamamoto S. Hum Mol Genet. 2018 Jul 15;27(14):2454-2465. doi: 10.1093/hmg/ddy146. PMID: 29726930 [PubMed - in process]
Summary: The authors begin by identifying four individuals from two families with heterozygous variants in the transcriptional regulator TBX2, who presented with craniofacial dysmorphisms, cardiac abnormalities, and developmental impairments. Further studies showed that both variants of TBX2 seen in the patients exhibited decreased expression levels of TBX2 in cultured cells and in vivo in Drosophila. Together, these studies demonstrate a role between TBX2 pathogenic alterations and human disorder.
Keywords: alleles; DiGeorge syndrome; congenital abnormality transcription; genetic mutation; cardiovascular system; cultured cells; chromosomes; developmental disabilities; Drosophila; genes; heterozygote; immune system; luciferases; brain; eye; heart; transcriptional repression; haploinsufficiency; deficiency; immune embryologic development; candidate disease gene; bioinformatics

An estimation of the prevalence of genomic disorders using chromosomal microarray data. Gillentine MA, Lupo PJ, Stankiewicz P, Schaaf CP.J Hum Genet. 2018 Jul;63(7):795-801. doi: 10.1038/s10038-018-0451-x. Epub 2018 Apr 24.PMID: 29691480 [PubMed - in process]
Summary: In this study, the authors develop a model to estimate the population prevalence of highly penetrant recurrent genomic disorders, for which there is currently sparse data owing to the rarity of such disorders. The utilization of CMA data to determine prevalence is a new approach that may be beneficial to apply to additional CNV-associated syndromes.
Keywords: genomic disorder; chromosome microarray; CMA; copy number variation; CNV; low copy repeat; 1q21.1 microdeletion and microduplication; 15q13.3 microdeletion; 16p11.2 microdeletion and microduplication

Mouse models as a tool for discovering new neurological diseases. Tan Q, Zoghbi HY. Neurobiol Learn Mem. 2018 Jul 17. pii: S1074-7427(18)30166-7. doi: 10.1016/j.nlm.2018.07.006. [Epub ahead of print] PMID: 30030131 [PubMed - as supplied by publisher]
Summary: This review discusses four examples where studying the consequences of altered gene dosage in a mouse led to the discovery of previously unrecognized human syndromes: MECP2 duplication syndrome, SHANK3 duplication syndrome, CIC haploinsufficiency syndrome, and PUM1-related disorders.
Keywords: CIC; MECP2; mouse model; neurological disease; PUM1; SHANK3

A glial blueprint for gliomagenesis. Laug D, Glasgow SM, Deneen B. Nat Rev Neurosci. 2018 Jul;19(7):393-403. doi: 10.1038/s41583-018-0014-3. Review. PMID: 29777182 [PubMed - in process]
Summary: This review explores glioma tumorigenesis through the lens of glial development, starting with the neurogenic-gliogenic switch and progressing through oligodendrocyte and astrocyte differentiation.
Keywords: oligodendrocyte differentiation; astrocyte differentiation; glioma; glia cells; glioma tumorigenesis

Impaired spatial memory codes in a mouse model of Rett syndrome. Kee SE, Mou X, Zoghbi HY, Ji D. Elife. 2018 Jul 20;7. pii: e31451. doi: 10.7554/eLife.31451. PMID: 30028675 [PubMed - in process] Free PMC Article
Summary: Recording from hippocampal place cells in freely moving Mecp2+/- mice, a mouse model for Rett Syndrome, the authors show that hypersynchronous firing, which interferes with ripple-dependent memory processing, may lead to impaired spatial memory coding.
Keywords: Rett syndrome; hippocampus; learning and memory; memory consolidation; mouse; neuroscience; place cells; ripples

Arginase overexpression in neurons and its effect on traumatic brain injury. Madan S, Kron B, Jin Z, Al Shamy G, Campeau PM, Sun Q, Chen S, Cherian L, Chen Y, Munivez E, Jiang MM, Robertson C, Goodman C, Ratan RR, Lee B. Mol Genet Metab. 2018 Jul 25. pii: S1096-7192(18)30279-8. doi: 10.1016/j.ymgme.2018.07.007. [Epub ahead of print] PMID: 30055993 [PubMed - as supplied by publisher]
Summary: Using two mouse models that genetically overexpress arginase only in neurons, the authors show that arginase I overexpression significantly reduced contusion size and index two weeks after a controlled cortical impact injury. This study demonstrates the importance of future studies exploring modulation of ariginase levels to improve outcomes of traumatic brain injury.
Keywords: arginase; arginine; nitric oxide; nitric oxide synthase; traumatic brain injury

Conditional loss of Kcnj13 in the retinal pigment epithelium causes photoreceptor degeneration. Roman D, Zhong H, Yaklichkin S, Chen R, Mardon G. Exp Eye Res. 2018 Jul 25;176:219-226. doi: 10.1016/j.exer.2018.07.014. [Epub ahead of print] PMID: 30009826 [PubMed - as supplied by publisher]
Summary: Here, the authors report two new tools that can be used to study the role of Kcnj13 in retinal homeostasis. Mice with homozygous deletion of Kcnj13 die at P1, so they generated a floxed, conditional loss-of-function Kcnj13flox allele. Further, they generated Kcnj13 conditional knockout reporter mice (Kcnj13 cKOR: Kcnj13flox/flox; Best1-cre; Ai9), allowing for live retinal fluorescence imaging.
Keywords: conditional knockout; KCNJ13; Kir7.1; Leber congenital amaurosis; photoreceptors; RPE; retinal degeneration; retinal function

Prematurity reduces citrulline-arginine-nitric oxide production and precedes the onset of necrotizing enterocolitis in piglets. Robinson JL, Smith VA, Stoll B, Agarwal U, Premkumar MH, Lau P, Cruz SM, Manjarin R, Olutoye OO, Burrin DG, Marini JC. Am J Physiol Gastrointest Liver Physiol. 2018 Jul 26. doi: 10.1152/ajpgi.00198.2018. [Epub ahead of print] PMID: 30048597 [PubMed - as supplied by publisher]
Summary: This study demonstrates that intestinal enzyme expression and whole body citrulline and arginine fluxes were reduced in pre-term piglets compared to animals of more advanced gestational age. Further, these reductions preceded the development of necrotizing enterocolitis (NEC).
Keywords: arginine; citrulline; necrotizing enterocolitis; nitric oxide; prematurity

Cognitive Behavioral Therapy for Childhood Anxiety Disorders: a Review of Recent Advances. Banneyer KN, Bonin L, Price K, Goodman WK, Storch EA. Curr Psychiatry Rep. 2018 Jul 28;20(8):65. doi: 10.1007/s11920-018-0924-9. Review. PMID: 30056623 [PubMed - in process]
Summary: This review examines recent research validating cognitive behavioral therapy (CBT) as a first-line intervention for childhood anxiety disorders. The authors also review recent research aimed at enhancing exposure-based CBT components and adapting CBT to work with specific populations.
Keywords: anxiety; children; cognitive behavior therapy

Epidemiology of anophthalmia and microphthalmia: Prevalence and patterns in Texas, 1999-2009. Chambers TM, Agopian AJ, Lewis RA, Langlois PH, Danysh HE, Weber KA, Shaw GM, Mitchell LE, Lupo PJ. Am J Med Genet A. 2018 Aug 2. doi: 10.1002/ajmg.a.40352. [Epub ahead of print]PMID: 30070760 [PubMed - as supplied by publisher]
Summary: This study expands our current understanding of the epidemiology of anophthalmia and microphthalmia and helps define subgroups of women who are more likely to have children with this malformation.
Keywords: anophthalmia; birth defects; epidemiology; eye defects; microphthalmia; prevalence

Combinatorial Prg4 and Il-1a gene therapy protects against hyperalgesia and cartilage degeneration in post-traumatic osteoarthritis. Stone AE, Grol MW, Ruan MZ, Dawson B, Chen Y, Jiang MM, Song IW, Jayaram P, Cela R, Gannon F, Lee BH.Hum Gene Ther. 2018 Aug 2. doi: 10.1089/hum.2018.106. [Epub ahead of print]PMID: 30070147 [PubMed - as supplied by publisher]
Summary: Here the authors demonstrate that using a combinatorial gene therapy approach to both inhibit inflammation and promote chondroprotection is more effective than either monotherapy for preservation of articular cartilage volume and therapy.
Keywords: osteoarthritis, degenerative disease, gene therapy, chrondroprotection, hyperalgesia, inflammation

Argininosuccinate Lyase Deficiency Causes an Endothelial-Dependent Form of Hypertension. Kho J, Tian X, Wong WT, Bertin T, Jiang MM, Chen S, Jin Z, Shchelochkov OA, Burrage LC, Reddy AK, Jiang H, Abo-Zahrah R, Ma S, Zhang P, Bissig KD, Kim JJ, Devaraj S, Rodney GG, Erez A, Bryan NS, Nagamani SCS, Lee BH. Am J Hum Genet. 2018 Aug 2;103(2):276-287. doi: 10.1016/j.ajhg.2018.07.008. PMID: 30075114 [PubMed - in process]
Summary: This study combines data from a human clinical study, a mouse model with endothelial-specific deletion of argininosuccinate lyase(Asl), and in vitro studies in human aortic endothelial cells and induced pluripotent stem cell-derived endothelial cells from individuals with ASLD, to show that loss of ASL in endothelial cells leads to endothelial-dependent vascular dysfunction with reduced nitric oxide (NO) production, increased oxidative stress, and impaired angiogenesis.
Keywords: Mendelian forms of hypertension; angiogenesis; argininosuccinate lyase; argininosuccinic aciduria; endothelial cells; endothelial dysfunction; hypertension; induced pluripotent stem cells; nitric oxide; oxidative stress

SPATA7 maintains a novel photoreceptor-specific zone in the distal connecting cilium. Dharmat R, Eblimit A, Robichaux MA, Zhang Z, Nguyen TT, Jung SY, He F, Jain A, Li Y, Qin J, Overbeek P, Roepman R, Mardon G, Wensel TG, Chen R. J Cell Biol. 2018 Aug 6;217(8):2851-2865. doi: 10.1083/jcb.201712117. Epub 2018 Jun 13. PMID: 29899041 [PubMed - in process]
Summary: Loss of Spata7 results in the mislocalization of the distal connecting cilium (DCC) without affecting the proximal connecting cilium (PCC). This collapse results in destabilization of the axonemal microtubules, which results in photoreceptor degeneration.
Keywords: SPATA7; photoreceptor; cilia; mutation; stochastic optical reconstruction microscopy; STORM

Translational Control in the Brain in Health and Disease. Sossin WS, Costa-Mattioli M. Cold Spring Harb Perspect Biol. 2018 Aug 6. pii: a032912. doi: 10.1101/cshperspect.a032912. [Epub ahead of print] PMID: 30082469 [PubMed - as supplied by publisher]
Summary: This review discusses general principles of neuronal translation, with a focus on eIF2A, mTORC1, and eEF2, in the context of both normal functioning of the nervous system, especially memory, and neurological disorders.
Keywords: translational control; mTORC1; synaptic plasticity; eIF2A; eEF2

An expanded toolkit for gene tagging based on MiMIC and scarless CRISPR tagging in Drosophila. Li-Kroeger D, Kanca O, Lee PT, Cowan S, Lee MT, Jaiswal M, Salazar JL, He Y, Zuo Z, Bellen HJ. Elife. 2018 Aug 9;7. pii: e38709. doi: 10.7554/eLife.38709. PMID: 30091705 [PubMed - in process] Free PMC Article
Summary: This report introduces two novel tools to fluorescently tag genes in Drosophila. Double Header (DH) doubles the efficiency of the current MiMIC system, and the second system uses CRISPR-Cas9 to introduce visible tags to genes without introns. Together, these approaches can be used to tag all genes in the fruit fly genome.
Keywords: D. melanogaster; double header; T2A-GAL4; Trojan exons; gene editing; genetics; genomics; protein tagging; swappable insertion cassette

Gene Therapy Rescues Retinal Degeneration in Reep6 Mutant Mice. Zaneveld SA, Eblimit A, Liang Q, Bertrand R, Wu N, Liu H, Nguyen Q, Zaneveld J, Wang K, Li Y, Chen R. Hum Gene Ther. 2018 Aug 13. doi: 10.1089/hum.2018.078. [Epub ahead of print]PMID: 30101608 [PubMed - as supplied by publisher]
Summary: Previously, the authors reported multiple families with autosomal recessive retinitis pigmentos had mutations in the REEP6 genes. Here, they generated REEP6 compound heterozygous mice and demonstrate a single AAV8 REEP6 delivery at post-natal day 20 improves the photo-response and preservation of photoreceptor cells at two months post-treatment. At one year post-injection, treated mice continue to show significant improvements in retinal function and morphology.
Keywords: retinal degeneration; REEP6; retinitis pigmentosa; retinal dystrophy; photoreceptor; gene therapy; AAV-8; autosomal recessive

Co-Occurring Posttraumatic Stress Disorder and Depression Among Young Children. Salloum A, Johnco C, Smyth KM, Murphy TK, Storch EA. Child Psychiatry Hum Dev. 2018 Jun;49(3):452-459. doi: 10.1007/s10578-017-0764-6. PMID: 29052121 [PubMed - in process]|
Summary: The purpose of this study was to examine differences in: (1) mental health emotional and behavioral problems between young children experiencing PTSD with and without MDD; (2) the incidence of caregiver PTSD and MDD between children with PTSD ± MDD; and (3) the number of traumatic events and interpersonal versus non-interpersonal nature of trauma events among children whose parents sought child trauma-focused treatment. Results indicated that young children with PTSD + MDD had significantly higher internalizing symptoms, dissociative symptoms, and post-traumatic stress severity than those without comorbid MDD. There were no significant group differences in the incidence of caregiver PTSD or MDD, or the number or types of traumatic events.
Keywords: comorbidity; depression; post-traumatic stress disorder; young children

PAK1 regulates ATXN1 levels providing an opportunity to modify its toxicity in spinocerebellar ataxia type 1. Bondar VV, Adamski CJ, Onur TS, Tan Q, Wang L, Diaz-Garcia J, Park J, Orr HT, Botas J, Zoghbi HY.Hum Mol Genet. 2018 Aug 15;27(16):2863-2873. doi: 10.1093/hmg/ddy200.PMID: 29860311 [PubMed - in process]
Summary: Spinocerebellar ataxia type 1 (SCA1) is caused by an expansion in the polyglutamine tract in ataxin-1 (ATXN1), which increases its accumulation and toxicity. Using a forward genetic screen in Drosophila, the authors identify p21-activated kinase 3 (Pak3) as a modulator of ATXN1. Loss-of-function studies in fly Pak3 or Pak1 and knockdown of Pak1 in mammalian cells show reduced levels of ATXN1. Further, pharmacological inhibition of PAKs decreased ATXN1 levels in a mouse model of SCA1. When combined with MSK1, a previously identified modulator of ATXN1, a further decrease in ATXN1 was seen, indicating a new avenue for potential therapeutics for SCA1.
Keywords: signal transduction; Drosophila; mammals; phosphorylation; phosphotransferases; genetics; mice; pathology; pharmacology; spinocerebellar ataxia type 1; toxic effect; polyglutamine

The Hippo pathway in the heart: pivotal roles in development, disease, and regeneration. Wang J, Liu S, Heallen T, Martin JF.Nat Rev Cardiol. 2018 Aug 15. doi: 10.1038/s41569-018-0063-3. [Epub ahead of print] Review. PMID: 30111784 [PubMed - as supplied by publisher]
Summary: This review discusses the roles of the evolutionarily conserved Hippo-YAP pathway, which controls organ size during prenatal and postnatal life. Importantly, manipulating the Hippo-YAP pathway is a potential therapeutic tool for treating cardiac injury.
Keywords: Yes-associated protein (YAP); Hippo-YAP; cardiomyocyte proliferation; cardiac regeneration; therapeutic target; cardiac injury

Mechanisms of skeletal muscle wasting in a mouse model for myotonic dystrophy type 1. Morriss GR, Rajapakshe K, Huang S, Coarfa C, Cooper TA. Hum Mol Genet. 2018 Aug 15;27(16):2789-2804. doi: 10.1093/hmg/ddy192. PMID: 29771332 [PubMed - in process]
Summary: To model myotonic dystrophy type 1 (DM1), the authors use an inducible skeletal muscle-specific model with 960 interrupted repeats in the context of human DMPK exons 11-15. Mice expressing CUG960 showed reduced muscle weight and histological myopathy consistent with DM1. Importantly, muscle loss and histological abnormalities are shown to be reversible upon removal of toxic RNA. Further analysis indicates that the balance between anabolic and catabolic pathways may be disrupted in this model through deregulation of PDGFR-β signaling and the PI3K/AKT pathways, and prolonged activation of AMP-activated protein kinase α signaling.
Keywords: myotonic dystrophy; cachexia; skeletal muscles; muscular atrophy; mice; RNA

NMNAT1 E257K variant, associated with Leber Congenital Amaurosis (LCA9), causes a mild retinal degeneration phenotype. Eblimit A, Zaneveld SA, Liu W, Thomas K, Wang K, Li Y, Mardon G, Chen R.Exp Eye Res. 2018 Aug;173:32-43. doi: 10.1016/j.exer.2018.04.010. Epub 2018 Apr 17.PMID: 29674119 [PubMed - in process]
Summary: Mutations in NMNAT1 have been identified in humans as playing a role in Leber Congenital Amaurosis 9 (LCA9). The authors created a knock-in mouse model, however the Nmnat1 E257K homozygous mice display no obvious morphological or functional defects up to one year old.
Keywords: NMNAT1; mutation; photoreceptor; retina

TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading. Martini-Stoica H, Cole AL, Swartzlander DB, Chen F, Wan YW, Bajaj L, Bader DA, Lee VMY, Trojanowski JQ, Liu Z, Sardiello M, Zheng H. J Exp Med. 2018 Sep 3;215(9):2355-2377. doi: 10.1084/jem.20172158. Epub 2018 Aug 14. PMID: 30108137 [PubMed - in process]
Summary: This study suggests that astrocytic Transcription Factor EB (TFEB) plays a functional role in modulating extracellular tau and the propagation of neuronal tau pathology in tauopathies such as Alzheimer's disease.
Keywords: Alzheimer’s; astrocyte; lysosomal biogenesis; tau pathology; hippocampus; mouse model

The Adhesion-GPCR BAI1 Promotes Excitatory Synaptogenesis by Coordinating Bidirectional Trans-synaptic Signaling. Tu YK, Duman JG, Tolias KF. J Neurosci. 2018 Aug 17. pii: 3461-17. doi: 10.1523/JNEUROSCI.3461-17.2018. [Epub ahead of print]
Summary: This study identifies three distinct signaling paradigms for BAI1, a post-synaptic A-GPCR, demonstrating that it mediates forward, reverse, and lateral signaling in spines. These findings establish BAI1 as a functional synaptogenic receptor that promotes pre- and post-synaptic development in cooperation with synaptic organizer NRLN1.
Keywords: adhesion-g protein-coupled receptors, BAI1, dendritic spines, excitatory synapses, development, Rac1, Neuroligin-1, synaptogenesis

mTOR-dependent phosphorylation controls TFEB nuclear export. Napolitano G, Esposito A, Choi H, Matarese M, Benedetti V, Di Malta C, Monfregola J, Medina DL, Lippincott-Schwartz J, Ballabio A. Nat Commun. 2018 Aug 17;9(1):3312. doi: 10.1038/s41467-018-05862-6. PMID: 30120233 [PubMed - in process] Free PMC Article
Summary: Transcription factor EB is known to play a pivotal role in organelle biogenesis and cell metabolism. Previously, it was shown that nutrient deprivation can induce TFEB activation through dephosphorylation and nuclear translocation, however the mechanism of its subsequent inactivation was unknown. The authors demonstrate that nutrient- and mTOR-dependent hierarchical phosphorylation of two serine residues near the nuclear export signal (NES) is necessary to induce TFEB nuclear export and inactivation.
Keywords: TOR signaling, lysosome, transcription factors, phosphorylation, nutrient availability

Faster processing of moving compared to flashed bars in awake macaque V1 provides a neural correlate of the flash lag illusion. Subramaniyan M, Ecker AS, Patel SS, Cotton RJ, Bethge M, Pitkow X, Berens P, Tolias A. J Neurophysiol. 2018 Aug 22. doi: 10.1152/jn.00792.2017. [Epub ahead of print] PMID: 30133378
Summary: Recording neural responses to flashed and moving bars revealed a decreased latency to moving bars, compared to flashed. These results suggest that the brain may have evolved mechanisms to process moving stimuli faster and closer to real time compared with briefly appearing stationary stimuli.
Keywords: flash lag illusion; latency; macaque; motion; v1

Novel deletion of 6p21.31p21.1 associated with laryngeal cleft, developmental delay, dysmorphic features and vascular anomaly. Pillai NR, Marafi D, Monteiro SA, Parnes M, Chandy BM, Patel A, Bacino CA, Breman AM, Burrage LC. Eur J Med Genet. 2018 Aug 22. pii: S1769-7212(18)30092-2. doi: 10.1016/j.ejmg.2018.08.012. [Epub ahead of print] PMID: 30142436 [PubMed - as supplied by publisher]
Summary: This articles describes a case of a 2-year-old girl with global developmental delay, severe speech delay, dysmorphic features, laryngeal cleft, anterior descending aorta that occluded the left main bronchus, and a novel de novo deletion involving chromosome region 6p21.31p21.2.
Keywords: 6p21.31; Aberrant descending aorta; Deletion; Developmental delay; Laryngeal cleft; Speech delay

Pitx2 maintains mitochondrial function during regeneration to prevent myocardial fat deposition. Li L, Tao G, Hill MC, Zhang M, Morikawa Y, Martin JF.Development. 2018 Aug 24. pii: dev.168609. doi: 10.1242/dev.168609. [Epub ahead of print]PMID: 30143541 [PubMed - as supplied by publisher]
Summary: These findings reveal a role for Pitx2 in maintaining proper cardiac cellular composition during heart regeneration via the maintenance of proper mitochondrial structure and function.
Keywords: Adipogenesis; Cardiac regeneration; Mitochondria; Mouse; Myocardial infarction

Rapid and Integrative Discovery of Retina Regulatory Molecules. Albrecht NE, Alevy J, Jiang D, Burger CA, Liu BI, Li F, Wang J, Kim SY, Hsu CW, Kalaga S, Udensi U, Asomugha C, Bohat R, Gaspero A, Justice MJ, Westenskow PD, Yamamoto S, Seavitt JR, Beaudet AL, Dickinson ME, Samuel MA. Cell Rep. 2018 Aug 28;24(9):2506-2519. doi: 10.1016/j.celrep.2018.07.090.PMID: 30157441 [PubMed - in process] Free Article
Summary: Using a novel high-throughput screening process called INSiGHT, the authors identified 16 unique retinal regulatory genes, 15 of which have not been previously associated with retinal organization.
Keywords: high-throughput screening; nervous system; neural disease; neuron; retina; synapse; vasculature; vision loss

The role of parental and perinatal characteristics on Langerhans cell histiocytosis: characterizing increased risk among Hispanics. Peckham-Gregory EC, McClain KL, Allen CE, Scheurer ME, Lupo PJ. Ann Epidemiol. 2018 Aug;28(8):521-528. doi: 10.1016/j.annepidem.2018.04.005. Epub 2018 Apr 17. PMID: 29724524 [PubMed - in process]
Summary: Langerhans cell histiocytosis (LCH), a myeloid neoplastic disorder, is characterized by somatic mutations in MAPK pathway genes in myeloid precursors. Searching for potential perinatal parental factors that associate with LCH risk, the authors find that children of Hispanic parents show an increased risk for LCH, suggesting the potential impact of inherited factors on LCH pathogenesis.
Keywords: epidemiology; Langerhans cell histiocytosis; race/ethnicity; risk factors; Texas Cancer Registry

Sensitized genetic backgrounds reveal differential roles for EGF repeat xylosyltransferases in Drosophila Notch signaling. Pandey A, Li-Kroeger D, Sethi MK, Lee TV, Buettner FFR, Bakker H, Jafar-Nejad H. Glycobiology. 2018 Aug 30. doi: 10.1093/glycob/cwy080. [Epub ahead of print] PMID: 30169771 [PubMed - as supplied by publisher]
Summary: The Notch pathway is a highly conserved developmental signaling pathway that can be regulated through glycosylation. The authors demonstrate that enhanced Notch signaling in shams mutants is primarily caused by the loss of the first xylose residue from O-glucose glycans on Notch EGF16-20, and that the second xylose can modulate Notch signaling when the level of Notch or Delta is limiting.
Keywords: Drosophila; notch signaling; glycosylation; developmental biology; xylosyltransferases; xylose

The regulation and function of the Hippo pathway in heart regeneration. Liu S, Martin JF.Wiley Interdiscip Rev Dev Biol. 2018 Aug 31:e335. doi: 10.1002/wdev.335. [Epub ahead of print] Review. PMID: 30169913 [PubMed - as supplied by publisher]
Summary: This article summarizes recent findings that have shed light on the function of the Hippo pathway in heart regeneration. The authors also discuss the mechanisms by which Hippo pathway inhibition promotes heart regeneration and how the Hippo pathway responds to different types of injury or stress during the regenerative process
Keywords: Hippo pathway; ROS; heart failure; heart regeneration; mechanical stress

RERE deficiency leads to decreased expression of GATA4 and the development of ventricular septal defects. Kim BJ, Zaveri HP, Jordan VK, Hernandez-Garcia A, Jacob DJ, Zamora DL, Yu W, Schwartz RJ, Scott DA. Dis Model Mech. 2018 Aug 28;11(9). pii: dmm031534. doi: 10.1242/dmm.031534. PMID: 30061196 [PubMed - in process] Free Article
Summary: RERE functions in the AV canal to positively regulate the expression of GATA4, and deficiency of RERE leads to the development of VSDs through its effects on EMT and mesenchymal cell proliferation. However, the cell-autonomous role of RERE in promoting EMT in the endocardium must be mediated by its effects on the expression of proteins other than GATA4.
Keywords: atrioventricular canal; atrioventricular cushion; endothelial-to-mesenchymal transition; GATA4; RERE; ventricular septal defects

Ex Vivo Enteroids Recapitulate In Vivo Citrulline Production in Mice. Wang X, Yuan Y, Didelija IC, Mohammad MA, Marini JC. J Nutr. 2018 Sep 1;148(9):1415-1420. doi: 10.1093/jn/nxy126. PMID: 30184221 [PubMed - in process]
Summary: This study demonstrates the utility of using enteroids to study in vivo citrulline production.
Keywords: arginine; citrulline; ornithine transcarbamylase; urea cycle; mutation; ex vivo; enteroids

Steroid Receptor Coactivator-2 Controls the Pentose Phosphate Pathway through RPIA in Human Endometrial Cancer Cells. Szwarc MM, Kommagani R, Putluri V, Dubrulle J, Stossi F, Mancini MA, Coarfa C, Lanz RB, Putluri N, DeMayo FJ, Lydon JP, O'Malley BW. Sci Rep. 2018 Sep 3;8(1):13134. doi: 10.1038/s41598-018-31372-y. PMID: 30177747 [PubMed - in process] Free PMC Article
Summary: This study examines the role of steroid receptor coactivator-2 (SRC-2) in human endometrial cancer (EC) cells. Knockdown of SRC-2 reduces EC cell proliferation and anchorage-independence. SRC-2 is also critical for the normal performance of the pentose phosphate pathway (PPP). Knockdown of both SRC-2 and ribose-5-p-isomerase (RPIA), a key enzyme of the PPP showed a novel regulatory cross-talk between glycolysis and the PPP.
Keywords: endometrial cancer; steroid receptor coactivator-2; pentose phosphate pathway; cancer; glycolysis

A druggable genome screen identifies modifiers of α-synuclein levels via a tiered cross-species validation approach. Rousseaux MWC, Vázquez-Vélez GE, Al-Ramahi I, Jeong HH, Bajic A, Revelli JP, Ye H, Phan ET, Deger JM, Perez AM, Kim JY, Lavery LA, Xu Q, Li MZ, Kang H, Kim JJ, Shulman JM, Westbrook TF, Elledge SJ, Liu Z, Botas J, Zoghbi HY.J Neurosci. 2018 Sep 24. pii: 0254-18. doi: 10.1523/JNEUROSCI.0254-18.2018. [Epub ahead of print] PMID: 30249792 [PubMed - as supplied by publisher]
Summary: This study presents a research strategy for the systematic identification and validation of genes modulating the levels of α-synuclein — a protein involved in Parkinson's disease.
Keywords:  a-synuclein; Parkinson’s disease; Lewy bodies; RNAi; Drosophila; genetics

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