Publications by authors named "Alyssa Ward"

13 Publications

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Global absence and targeting of protective immune states in severe COVID-19.

Nature 2021 03 25;591(7848):124-130. Epub 2021 Jan 25.

Department of Pathology, University of California San Francisco, San Francisco, CA, USA.

Although infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has pleiotropic and systemic effects in some individuals, many others experience milder symptoms. Here, to gain a more comprehensive understanding of the distinction between severe and mild phenotypes in the pathology of coronavirus disease 2019 (COVID-19) and its origins, we performed a whole-blood-preserving single-cell analysis protocol to integrate contributions from all major immune cell types of the blood-including neutrophils, monocytes, platelets, lymphocytes and the contents of the serum. Patients with mild COVID-19 exhibit a coordinated pattern of expression of interferon-stimulated genes (ISGs) across every cell population, whereas these ISG-expressing cells are systemically absent in patients with severe disease. Paradoxically, individuals with severe COVID-19 produce very high titres of anti-SARS-CoV-2 antibodies and have a lower viral load compared to individuals with mild disease. Examination of the serum from patients with severe COVID-19 shows that these patients uniquely produce antibodies that functionally block the production of the ISG-expressing cells associated with mild disease, by activating conserved signalling circuits that dampen cellular responses to interferons. Overzealous antibody responses pit the immune system against itself in many patients with COVID-19, and perhaps also in individuals with other viral infections. Our findings reveal potential targets for immunotherapies in patients with severe COVID-19 to re-engage viral defence.
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http://dx.doi.org/10.1038/s41586-021-03234-7DOI Listing
March 2021

Global Absence and Targeting of Protective Immune States in Severe COVID-19.

bioRxiv 2020 Oct 29. Epub 2020 Oct 29.

While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies with multiple patterns of specificity against interferon-stimulated cells and that those antibodies functionally block the production of the mild disease-associated ISG-expressing cells. Overzealous and auto-directed antibody responses pit the immune system against itself in many COVID-19 patients and this defines targets for immunotherapies to allow immune systems to provide viral defense.

One Sentence Summary: In severe COVID-19 patients, the immune system fails to generate cells that define mild disease; antibodies in their serum actively prevents the successful production of those cells.
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http://dx.doi.org/10.1101/2020.10.28.359935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605559PMC
October 2020

Global Absence and Targeting of Protective Immune States in Severe COVID-19.

Res Sq 2020 Oct 28. Epub 2020 Oct 28.

Department of Pathology, San Francisco, 513 Parnassus Ave, HSW512, San Francisco, CA 94143-0511, USA.

While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a wholeblood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferonstimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies with multiple patterns of specificity against interferon-stimulated cells and that those antibodies functionally block the production of the mild disease-associated ISG-expressing cells. Overzealous and autodirected antibody responses pit the immune system against itself in many COVID-19 patients and this defines targets for immunotherapies to allow immune systems to provide viral defense.
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http://dx.doi.org/10.21203/rs.3.rs-97042/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605560PMC
October 2020

Discussions of miscarriage and preterm births on Twitter.

Paediatr Perinat Epidemiol 2020 09 8;34(5):544-552. Epub 2020 Jan 8.

Department of Global Health, School of Public Health, Boston University, Boston, MA, USA.

Background: Experiences typically considered private, such as, miscarriages and preterm births are being discussed publicly on social media and Internet discussion websites. These data can provide timely illustrations of how individuals discuss miscarriages and preterm births, as well as insights into the wellbeing of women who have experienced a miscarriage.

Objectives: To characterise how users discuss the topic of miscarriage and preterm births on Twitter, analyse trends and drivers, and describe the perceived emotional state of women who have experienced a miscarriage.

Methods: We obtained 291 443 Twitter postings on miscarriages and preterm births from January 2017 through December 2018. Latent Dirichlet Allocation (LDA) was used to identify major topics of discussion. We applied time series decomposition methods to assess temporal trends and identify major drivers of discussion. Furthermore, four coders labelled the emotional content of 7282 personal miscarriage disclosure tweets into the following non-mutually exclusive categories: grief/sadness/depression, anger, relief, isolation, annoyance, and neutral.

Results: Topics in our data fell into eight groups: celebrity disclosures, Michelle Obama's disclosure, politics, healthcare, preterm births, loss and anxiety, flu vaccine and ectopic pregnancies. Political discussions around miscarriages were largely due to a misunderstanding between abortions and miscarriages. Grief and annoyance were the most commonly expressed emotions within the miscarriage self-disclosures; 50.6% (95% confidence interval [CI] 49.1, 52.2) and 16.2% (95% CI 15.2, 17.3). Postings increased with celebrity disclosures, pharmacists' refusal of prescribed medications and outrage over the high rate of preterm births in the United States. Miscarriage disclosures by celebrities also led to disclosures by women who had similar experiences.

Conclusions: This study suggests that increase in discussions of miscarriage on social media are associated with several factors, including celebrity disclosures. Additionally, there is a misunderstanding of the potential physical, emotional and psychological impacts on individuals who lose a pregnancy due to a miscarriage.
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http://dx.doi.org/10.1111/ppe.12622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496231PMC
September 2020

The RAG-2 Inhibitory Domain Gates Accessibility of the V(D)J Recombinase to Chromatin.

Mol Cell Biol 2018 08 16;38(15). Epub 2018 Jul 16.

Department of Molecular Biology and Genetics and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Accessibility of antigen receptor loci to RAG is correlated with the presence of H3K4me3, which binds to a plant homeodomain (PHD) in the RAG-2 subunit and promotes V(D)J recombination. A point mutation in the PHD, W453A, eliminates binding of H3K4me3 and impairs recombination. The debilitating effect of the W453A mutation is ameliorated by second-site mutations that locate an inhibitory domain in the interval from residues 352 through 405 of RAG-2. Disruption of the inhibitory domain stimulates V(D)J recombination within extrachromosomal substrates and at endogenous antigen receptor loci. Association of RAG-1 and RAG-2 with chromatin at the locus in B cell progenitors is dependent on recognition of H3K4me3 by the PHD. Strikingly, disruption of the inhibitory domain permits association of RAG with the locus in the absence of H3K4me3 binding. Thus, the inhibitory domain acts as a gate that prohibits RAG from accessing the locus unless RAG-2 is engaged by H3K4me3.
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http://dx.doi.org/10.1128/MCB.00159-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048317PMC
August 2018

Social, economic, and policy implications of organ preservation advances.

Curr Opin Organ Transplant 2018 06;23(3):336-346

Organ Preservation Alliance, NASA Research Park, Moffett Field, Los Altos, California.

Purpose Of Review: Despite over 60 years of progress in the field of since the first organ transplant, insufficient organ preservation capabilities still place profound constraints on transplantation. These constraints play multiple and compounding roles in the predominant limitations of the field: the severe shortages of transplant organs, short-term and long-term posttransplant outcomes and complications, the unmet global need for development of transplant infrastructures, and economic burdens that limit patient access to transplantation and contribute to increasing global healthcare costs. This review surveys ways that advancing preservation technologies can play a role in each of these areas, ultimately benefiting thousands if not millions of patients worldwide.

Recent Findings: Preservation advances can create a wide range of benefits across many facets of organ transplantation, as well as related areas of transplant research. As these technologies mature, so will the policies around their use to maximize the benefits offered by organ preservation.

Summary: Organ preservation advances stand to increase local and global access to transplantation, improve transplant outcomes, and accelerate progress in related areas such as immune tolerance induction and xenotransplantation. This area holds the potential to save the healthcare system many billions of dollars and reduce costs across many aspects of transplantation. Novel preservation technologies, along with other technologies facilitated by preservation advances, could potentially save millions of lives in the coming years.
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http://dx.doi.org/10.1097/MOT.0000000000000532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959266PMC
June 2018

Child STEPs in California: A cluster randomized effectiveness trial comparing modular treatment with community implemented treatment for youth with anxiety, depression, conduct problems, or traumatic stress.

J Consult Clin Psychol 2017 Jan 22;85(1):13-25. Epub 2016 Aug 22.

Department of Psychology, University of California, Los Angeles.

Objective: This study reports outcomes from a randomized effectiveness trial testing modular treatment versus multiple community-implemented evidence-based treatments for youth.

Method: An ethnoracially diverse sample of 138 youth ages 5 to 15 (62 girls, 76 boys) whose primary clinical concerns involved diagnoses or clinical elevations related to anxiety, depression, disruptive behavior, and/or traumatic stress were treated by community therapists randomly assigned to 1 of 2 conditions: (a) modular treatment, which involved a single modular protocol (i.e., modular approach to therapy for children; MATCH) that allowed flexible selection and sequencing of procedures to fit the chosen treatment focus in the context of measurement feedback, and (b) community-implemented treatment (CIT), which was a county-supported implementation of multiple evidence-based practices for youth.

Results: Youth treated with MATCH showed significantly faster rates of improvement over time on clinical and functional outcomes relative to youth in the CIT condition and required significantly fewer sessions delivered over significantly fewer days. Caregiver-reported clinical improvement rates were significantly greater for MATCH (60%) versus CIT (36.7%). Further, youth in the CIT condition were significantly more likely to receive additional psychosocial treatment services and were significantly more likely to use a variety of psychotropic medications during the active treatment phase.

Conclusions: These results extend prior findings, supporting the effectiveness and efficiency of a modular, multifocus approach that incorporates monitoring and feedback relative to community implementation of evidence-based treatments. (PsycINFO Database Record
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http://dx.doi.org/10.1037/ccp0000133DOI Listing
January 2017

Research data: Silver lining to irreproducibility.

Nature 2016 Apr;532(7598):177

University of Arizona, Tucson, USA.

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http://dx.doi.org/10.1038/532177dDOI Listing
April 2016

Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.

Authors:
Wilson Leung Christopher D Shaffer Laura K Reed Sheryl T Smith William Barshop William Dirkes Matthew Dothager Paul Lee Jeannette Wong David Xiong Han Yuan James E J Bedard Joshua F Machone Seantay D Patterson Amber L Price Bryce A Turner Srebrenka Robic Erin K Luippold Shannon R McCartha Tezin A Walji Chelsea A Walker Kenneth Saville Marita K Abrams Andrew R Armstrong William Armstrong Robert J Bailey Chelsea R Barberi Lauren R Beck Amanda L Blaker Christopher E Blunden Jordan P Brand Ethan J Brock Dana W Brooks Marie Brown Sarah C Butzler Eric M Clark Nicole B Clark Ashley A Collins Rebecca J Cotteleer Peterson R Cullimore Seth G Dawson Carter T Docking Sasha L Dorsett Grace A Dougherty Kaitlyn A Downey Andrew P Drake Erica K Earl Trevor G Floyd Joshua D Forsyth Jonathan D Foust Spencer L Franchi James F Geary Cynthia K Hanson Taylor S Harding Cameron B Harris Jonathan M Heckman Heather L Holderness Nicole A Howey Dontae A Jacobs Elizabeth S Jewell Maria Kaisler Elizabeth A Karaska James L Kehoe Hannah C Koaches Jessica Koehler Dana Koenig Alexander J Kujawski Jordan E Kus Jennifer A Lammers Rachel R Leads Emily C Leatherman Rachel N Lippert Gregory S Messenger Adam T Morrow Victoria Newcomb Haley J Plasman Stephanie J Potocny Michelle K Powers Rachel M Reem Jonathan P Rennhack Katherine R Reynolds Lyndsey A Reynolds Dong K Rhee Allyson B Rivard Adam J Ronk Meghan B Rooney Lainey S Rubin Luke R Salbert Rasleen K Saluja Taylor Schauder Allison R Schneiter Robert W Schulz Karl E Smith Sarah Spencer Bryant R Swanson Melissa A Tache Ashley A Tewilliager Amanda K Tilot Eve VanEck Matthew M Villerot Megan B Vylonis David T Watson Juliana A Wurzler Lauren M Wysocki Monica Yalamanchili Matthew A Zaborowicz Julia A Emerson Carlos Ortiz Frederic J Deuschle Lauren A DiLorenzo Katie L Goeller Christopher R Macchi Sarah E Muller Brittany D Pasierb Joseph E Sable Jessica M Tucci Marykathryn Tynon David A Dunbar Levent H Beken Alaina C Conturso Benjamin L Danner Gabriella A DeMichele Justin A Gonzales Maureen S Hammond Colleen V Kelley Elisabeth A Kelly Danielle Kulich Catherine M Mageeney Nikie L McCabe Alyssa M Newman Lindsay A Spaeder Richard A Tumminello Dennis Revie Jonathon M Benson Michael C Cristostomo Paolo A DaSilva Katherine S Harker Jenifer N Jarrell Luis A Jimenez Brandon M Katz William R Kennedy Kimberly S Kolibas Mark T LeBlanc Trung T Nguyen Daniel S Nicolas Melissa D Patao Shane M Patao Bryan J Rupley Bridget J Sessions Jennifer A Weaver Anya L Goodman Erica L Alvendia Shana M Baldassari Ashley S Brown Ian O Chase Maida Chen Scott Chiang Avery B Cromwell Ashley F Custer Tia M DiTommaso Jad El-Adaimi Nora C Goscinski Ryan A Grove Nestor Gutierrez Raechel S Harnoto Heather Hedeen Emily L Hong Barbara L Hopkins Vilma F Huerta Colin Khoshabian Kristin M LaForge Cassidy T Lee Benjamin M Lewis Anniken M Lydon Brian J Maniaci Ryan D Mitchell Elaine V Morlock William M Morris Priyanka Naik Nicole C Olson Jeannette M Osterloh Marcos A Perez Jonathan D Presley Matt J Randazzo Melanie K Regan Franca G Rossi Melanie A Smith Eugenia A Soliterman Ciani J Sparks Danny L Tran Tiffany Wan Anne A Welker Jeremy N Wong Aparna Sreenivasan Jim Youngblom Andrew Adams Justin Alldredge Ashley Bryant David Carranza Alyssa Cifelli Kevin Coulson Calise Debow Noelle Delacruz Charlene Emerson Cassandra Farrar Don Foret Edgar Garibay John Gooch Michelle Heslop Sukhjit Kaur Ambreen Khan Van Kim Travis Lamb Peter Lindbeck Gabi Lucas Elizabeth Macias Daniela Martiniuc Lissett Mayorga Joseph Medina Nelson Membreno Shady Messiah Lacey Neufeld San Francisco Nguyen Zachary Nichols George Odisho Daymon Peterson Laura Rodela Priscilla Rodriguez Vanessa Rodriguez Jorge Ruiz Will Sherrill Valeria Silva Jeri Sparks Geeta Statton Ashley Townsend Isabel Valdez Mary Waters Kyle Westphal Stacey Winkler Joannee Zumkehr Randall J DeJong Arlene J Hoogewerf Cheri M Ackerman Isaac O Armistead Lara Baatenburg Matthew J Borr Lindsay K Brouwer Brandon J Burkhart Kelsey T Bushhouse Lejla Cesko Tiffany Y Y Choi Heather Cohen Amanda M Damsteegt Jess M Darusz Cory M Dauphin Yelena P Davis Emily J Diekema Melissa Drewry Michelle E M Eisen Hayley M Faber Katherine J Faber Elizabeth Feenstra Isabella T Felzer-Kim Brandy L Hammond Jesse Hendriksma Milton R Herrold Julia A Hilbrands Emily J Howell Sarah A Jelgerhuis Timothy R Jelsema Benjamin K Johnson Kelly K Jones Anna Kim Ross D Kooienga Erika E Menyes Eric A Nollet Brittany E Plescher Lindsay Rios Jenny L Rose Allison J Schepers Geoff Scott Joshua R Smith Allison M Sterling Jenna C Tenney Chris Uitvlugt Rachel E VanDyken Marielle VanderVennen Samantha Vue Nighat P Kokan Kwabea Agbley Sampson K Boham Daniel Broomfield Kayla Chapman Ali Dobbe Ian Dobbe William Harrington Marwan Ibrahem Andre Kennedy Chad A Koplinsky Cassandra Kubricky Danielle Ladzekpo Claire Pattison Roman E Ramirez Lucia Wande Sarah Woehlke Matthew Wawersik Elizabeth Kiernan Jeffrey S Thompson Roxanne Banker Justina R Bartling Chinmoy I Bhatiya Anna L Boudoures Lena Christiansen Daniel S Fosselman Kristin M French Ishwar S Gill Jessen T Havill Jaelyn L Johnson Lauren J Keny John M Kerber Bethany M Klett Christina N Kufel Francis J May Jonathan P Mecoli Callie R Merry Lauren R Meyer Emily G Miller Gregory J Mullen Katherine C Palozola Jacob J Pfeil Jessica G Thomas Evan M Verbofsky Eric P Spana Anant Agarwalla Julia Chapman Ben Chlebina Insun Chong I N Falk John D Fitzgibbons Harrison Friedman Osagie Ighile Andrew J Kim Kristin A Knouse Faith Kung Danny Mammo Chun Leung Ng Vinayak S Nikam Diana Norton Philip Pham Jessica W Polk Shreya Prasad Helen Rankin Camille D Ratliff Victoria Scala Nicholas U Schwartz Jessica A Shuen Amy Xu Thomas Q Xu Yi Zhang Anne G Rosenwald Martin G Burg Stephanie J Adams Morgan Baker Bobbi Botsford Briana Brinkley Carter Brown Shadie Emiah Erica Enoch Chad Gier Alyson Greenwell Lindsay Hoogenboom Jordan E Matthews Mitchell McDonald Amanda Mercer Nicholaus Monsma Kristine Ostby Alen Ramic Devon Shallman Matthew Simon Eric Spencer Trisha Tomkins Pete Wendland Anna Wylie Michael J Wolyniak Gregory M Robertson Samuel I Smith Justin R DiAngelo Eric D Sassu Satish C Bhalla Karim A Sharif Tenzin Choeying Jason S Macias Fareed Sanusi Karvyn Torchon April E Bednarski Consuelo J Alvarez Kristen C Davis Carrie A Dunham Alaina J Grantham Amber N Hare Jennifer Schottler Zackary W Scott Gary A Kuleck Nicole S Yu Marian M Kaehler Jacob Jipp Paul J Overvoorde Elizabeth Shoop Olivia Cyrankowski Betsy Hoover Matt Kusner Devry Lin Tijana Martinov Jonathan Misch Garrett Salzman Holly Schiedermayer Michael Snavely Stephanie Zarrasola Susan Parrish Atlee Baker Alissa Beckett Carissa Belella Julie Bryant Turner Conrad Adam Fearnow Carolina Gomez Robert A Herbstsomer Sarah Hirsch Christen Johnson Melissa Jones Rita Kabaso Eric Lemmon Carolina Marques Dos Santos Vieira Darryl McFarland Christopher McLaughlin Abbie Morgan Sepo Musokotwane William Neutzling Jana Nietmann Christina Paluskievicz Jessica Penn Emily Peoples Caitlin Pozmanter Emily Reed Nichole Rigby Lasse Schmidt Micah Shelton Rebecca Shuford Tiara Tirasawasdichai Blair Undem Damian Urick Kayla Vondy Bryan Yarrington Todd T Eckdahl Jeffrey L Poet Alica B Allen John E Anderson Jason M Barnett Jordan S Baumgardner Adam D Brown Jordan E Carney Ramiro A Chavez Shelbi L Christgen Jordan S Christie Andrea N Clary Michel A Conn Kristen M Cooper Matt J Crowley Samuel T Crowley Jennifer S Doty Brian A Dow Curtis R Edwards Darcie D Elder John P Fanning Bridget M Janssen Anthony K Lambright Curtiss E Lane Austin B Limle Tammy Mazur Marly R McCracken Alexa M McDonough Amy D Melton Phillip J Minnick Adam E Musick William H Newhart Joseph W Noynaert Bradley J Ogden Michael W Sandusky Samantha M Schmuecker Anna L Shipman Anna L Smith Kristen M Thomsen Matthew R Unzicker William B Vernon Wesley W Winn Dustin S Woyski Xiao Zhu Chunguang Du Caitlin Ament Soham Aso Laura Simone Bisogno Jason Caronna Nadezhda Fefelova Lenin Lopez Lorraine Malkowitz Jonathan Marra Daniella Menillo Ifeanyi Obiorah Eric Nyabeta Onsarigo Shekerah Primus Mahdi Soos Archana Tare Ameer Zidan Christopher J Jones Todd Aronhalt James M Bellush Christa Burke Steve DeFazio Benjamin R Does Todd D Johnson Nicholas Keysock Nelson H Knudsen James Messler Kevin Myirski Jade Lea Rekai Ryan Michael Rempe Michael S Salgado Erica Stagaard Justin R Starcher Andrew W Waggoner Anastasia K Yemelyanova Amy T Hark Anne Bertolet Cyrus E Kuschner Kesley Parry Michael Quach Lindsey Shantzer Mary E Shaw Mary A Smith Omolara Glenn Portia Mason Charlotte Williams S Catherine Silver Key Tyneshia C P Henry Ashlee G Johnson Jackie X White Adam Haberman Sam Asinof Kelly Drumm Trip Freeburg Nadia Safa Darrin Schultz Yakov Shevin Petros Svoronos Tam Vuong Jules Wellinghoff Laura L M Hoopes Kim M Chau Alyssa Ward E Gloria C Regisford LaJerald Augustine Brionna Davis-Reyes Vivienne Echendu Jasmine Hales Sharon Ibarra Lauriaun Johnson Steven Ovu John M Braverman Thomas J Bahr Nicole M Caesar Christopher Campana Daniel W Cassidy Peter A Cognetti Johnathan D English Matthew C Fadus Cameron N Fick Philip J Freda Bryan M Hennessy Kelsey Hockenberger Jennifer K Jones Jessica E King Christopher R Knob Karen J Kraftmann Linghui Li Lena N Lupey Carl J Minniti Thomas F Minton Joseph V Moran Krishna Mudumbi Elizabeth C Nordman William J Puetz Lauren M Robinson Thomas J Rose Edward P Sweeney Ashley S Timko Don W Paetkau Heather L Eisler Megan E Aldrup Jessica M Bodenberg Mara G Cole Kelly M Deranek Megan DeShetler Rose M Dowd Alexandra K Eckardt Sharon C Ehret Jessica Fese Amanda D Garrett Anna Kammrath Michelle L Kappes Morgan R Light Anne C Meier Allison O'Rouke Mallory Perella Kimberley Ramsey Jennifer R Ramthun Mary T Reilly Deirdre Robinett Nadine L Rossi Mary Grace Schueler Emma Shoemaker Kristin M Starkey Ashley Vetor Abby Vrable Vidya Chandrasekaran Christopher Beck Kristen R Hatfield Douglas A Herrick Christopher B Khoury Charlotte Lea Christopher A Louie Shannon M Lowell Thomas J Reynolds Jeanine Schibler Alexandra H Scoma Maxwell T Smith-Gee Sarah Tuberty Christopher D Smith Jane E Lopilato Jeanette Hauke Jennifer A Roecklein-Canfield Maureen Corrielus Hannah Gilman Stephanie Intriago Amanda Maffa Sabya A Rauf Katrina Thistle Melissa Trieu Jenifer Winters Bib Yang Charles R Hauser Tariq Abusheikh Yara Ashrawi Pedro Benitez Lauren R Boudreaux Megan Bourland Miranda Chavez Samantha Cruz GiNell Elliott Jesse R Farek Sarah Flohr Amanda H Flores Chelsey Friedrichs Zach Fusco Zane Goodwin Eric Helmreich John Kiley John Mark Knepper Christine Langner Megan Martinez Carlos Mendoza Monal Naik Andrea Ochoa Nicolas Ragland England Raimey Sunil Rathore Evangelina Reza Griffin Sadovsky Marie-Isabelle B Seydoux Jonathan E Smith Anna K Unruh Vicente Velasquez Matthew W Wolski Yuying Gosser Shubha Govind Nicole Clarke-Medley Leslie Guadron Dawn Lau Alvin Lu Cheryl Mazzeo Mariam Meghdari Simon Ng Brad Pamnani Olivia Plante Yuki Kwan Wa Shum Roy Song Diana E Johnson Mai Abdelnabi Alexi Archambault Norma Chamma Shailly Gaur Deborah Hammett Adrese Kandahari Guzal Khayrullina Sonali Kumar Samantha Lawrence Nigel Madden Max Mandelbaum Heather Milnthorp Shiv Mohini Roshni Patel Sarah J Peacock Emily Perling Amber Quintana Michael Rahimi Kristen Ramirez Rishi Singhal Corinne Weeks Tiffany Wong Aubree T Gillis Zachary D Moore Christopher D Savell Reece Watson Stephanie F Mel Arjun A Anilkumar Paul Bilinski Rostislav Castillo Michael Closser Nathalia M Cruz Tiffany Dai Giancarlo F Garbagnati Lanor S Horton Dongyeon Kim Joyce H Lau James Z Liu Sandy D Mach Thu A Phan Yi Ren Kenneth E Stapleton Jean M Strelitz Ray Sunjed Joyce Stamm Morgan C Anderson Bethany Grace Bonifield Daniel Coomes Adam Dillman Elaine J Durchholz Antoinette E Fafara-Thompson Meleah J Gross Amber M Gygi Lesley E Jackson Amy Johnson Zuzana Kocsisova Joshua L Manghelli Kylie McNeil Michael Murillo Kierstin L Naylor Jessica Neely Emmy E Ogawa Ashley Rich Anna Rogers J Devin Spencer Kristina M Stemler Allison A Throm Matt Van Camp Katie Weihbrecht T Aaron Wiles Mallory A Williams Matthew Williams Kyle Zoll Cheryl Bailey Leming Zhou Darla M Balthaser Azita Bashiri Mindy E Bower Kayla A Florian Nazanin Ghavam Elizabeth S Greiner-Sosanko Helmet Karim Victor W Mullen Carly E Pelchen Paul M Yenerall Jiayu Zhang Michael R Rubin Suzette M Arias-Mejias Armando G Bermudez-Capo Gabriela V Bernal-Vega Mariela Colon-Vazquez Arelys Flores-Vazquez Mariela Gines-Rosario Ivan G Llavona-Cartagena Javier O Martinez-Rodriguez Lionel Ortiz-Fuentes Eliezer O Perez-Colomba Joseph Perez-Otero Elisandra Rivera Luke J Rodriguez-Giron Arnaldo J Santiago-Sanabria Andrea M Senquiz-Gonzalez Frank R Soto delValle Dorianmarie Vargas-Franco Karla I Velázquez-Soto Joan D Zambrana-Burgos Juan Carlos Martinez-Cruzado Lillyann Asencio-Zayas Kevin Babilonia-Figueroa Francis D Beauchamp-Pérez Juliana Belén-Rodríguez Luciann Bracero-Quiñones Andrea P Burgos-Bula Xavier A Collado-Méndez Luis R Colón-Cruz Ana I Correa-Muller Jonathan L Crooke-Rosado José M Cruz-García Marianna Defendini-Ávila Francheska M Delgado-Peraza Alex J Feliciano-Cancela Valerie M Gónzalez-Pérez Wilfried Guiblet Aldo Heredia-Negrón Jennifer Hernández-Muñiz Lourdes N Irizarry-González Ángel L Laboy-Corales Gabriela A Llaurador-Caraballo Frances Marín-Maldonado Ulises Marrero-Llerena Héctor A Martell-Martínez Idaliz M Martínez-Traverso Kiara N Medina-Ortega Sonya G Méndez-Castellanos Krizia C Menéndez-Serrano Carol I Morales-Caraballo Saryleine Ortiz-DeChoudens Patricia Ortiz-Ortiz Hendrick Pagán-Torres Diana Pérez-Afanador Enid M Quintana-Torres Edwin G Ramírez-Aponte Carolina Riascos-Cuero Michelle S Rivera-Llovet Ingrid T Rivera-Pagán Ramón E Rivera-Vicéns Fabiola Robles-Juarbe Lorraine Rodríguez-Bonilla Brian O Rodríguez-Echevarría Priscila M Rodríguez-García Abneris E Rodríguez-Laboy Susana Rodríguez-Santiago Michael L Rojas-Vargas Eva N Rubio-Marrero Albeliz Santiago-Colón Jorge L Santiago-Ortiz Carlos E Santos-Ramos Joseline Serrano-González Alina M Tamayo-Figueroa Edna P Tascón-Peñaranda José L Torres-Castillo Nelson A Valentín-Feliciano Yashira M Valentín-Feliciano Nadyan M Vargas-Barreto Miguel Vélez-Vázquez Luis R Vilanova-Vélez Cristina Zambrana-Echevarría Christy MacKinnon Hui-Min Chung Chris Kay Anthony Pinto Olga R Kopp Joshua Burkhardt Chris Harward Robert Allen Pavan Bhat Jimmy Hsiang-Chun Chang York Chen Christopher Chesley Dara Cohn David DuPuis Michael Fasano Nicholas Fazzio Katherine Gavinski Heran Gebreyesus Thomas Giarla Marcus Gostelow Rachel Greenstein Hashini Gunasinghe Casey Hanson Amanda Hay Tao Jian He Katie Homa Ruth Howe Jeff Howenstein Henry Huang Aaditya Khatri Young Lu Kim Olivia Knowles Sarah Kong Rebecca Krock Matt Kroll Julia Kuhn Matthew Kwong Brandon Lee Ryan Lee Kevin Levine Yedda Li Bo Liu Lucy Liu Max Liu Adam Lousararian Jimmy Ma Allyson Mallya Charlie Manchee Joseph Marcus Stephen McDaniel Michelle L Miller Jerome M 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Miller Cody M Morrow Julia C Peairs Gentry L Pickett Sarah A Popelka Alexis J Scott Emily J Teepe Katie A TerMeer Carmen A Watchinski Lucas A Watson Rachel E Weber Kate A Woodard Daron C Barnard Isaac Appiah Michelle M Giddens Gerard P McNeil Adeola Adebayo Kate Bagaeva Justina Chinwong Chrystel Dol Eunice George Kirk Haltaufderhyde Joanna Haye Manpreet Kaur Max Semon Dmitri Serjanov Anika Toorie Christopher Wilson Nicole C Riddle Jeremy Buhler Elaine R Mardis Sarah C R Elgin

G3 (Bethesda) 2015 Mar 4;5(5):719-40. Epub 2015 Mar 4.

Department of Biology, Washington University in St. Louis, St. Louis, MO 63130

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.
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http://dx.doi.org/10.1534/g3.114.015966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426361PMC
March 2015

An autoregulatory mechanism imposes allosteric control on the V(D)J recombinase by histone H3 methylation.

Cell Rep 2015 Jan 24;10(1):29-38. Epub 2014 Dec 24.

Department of Molecular Biology and Genetics and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:

V(D)J recombination is initiated by a specialized transposase consisting of the subunits RAG-1 and RAG-2. The susceptibility of gene segments to DNA cleavage by the V(D)J recombinase is correlated with epigenetic modifications characteristic of active chromatin, including trimethylation of histone H3 on lysine 4 (H3K4me3). Engagement of H3K4me3 by a plant homeodomain (PHD) in RAG-2 promotes recombination in vivo and stimulates DNA cleavage by RAG in vitro. We now show that H3K4me3 acts allosterically at the PHD finger to relieve autoinhibition imposed by a separate domain within RAG-2. Disruption of this autoinhibitory domain was associated with constitutive increases in recombination frequency, DNA cleavage activity, substrate binding affinity, and catalytic rate, thus mimicking the stimulatory effects of H3K4me3. Our observations support a model in which allosteric control of RAG is enforced by an autoinhibitory domain whose action is relieved by engagement of active chromatin.
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http://dx.doi.org/10.1016/j.celrep.2014.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308961PMC
January 2015

Long-term outcomes for the Child STEPs randomized effectiveness trial: a comparison of modular and standard treatment designs with usual care.

J Consult Clin Psychol 2013 Dec 26;81(6):999-1009. Epub 2013 Aug 26.

Department of Psychology, University of California.

Objective: This article reports outcomes from the Child STEPs randomized effectiveness trial conducted over a 2-year period to gauge the longer term impact of protocol design on the effectiveness of evidence-based treatment procedures.

Method: An ethnoracially diverse sample of 174 youths ages 7- 13 (N = 121 boys) whose primary clinical concerns involved diagnoses or clinical elevations related to anxiety, depression, or disruptive behavior were treated by community therapists randomly assigned to 1 of 3 conditions: (a) standard, which involved the use of 1 or more of 3 manualized evidence-based treatments, (b) modular, which involved a single modular protocol (Modular Approach to Treatment of Children With Anxiety, Depression, or Conduct Problems; MATCH) having clinical procedures similar to the standard condition but flexibly selected and sequenced using a guiding clinical algorithm, and (c) usual care.

Results: As measured with combined Child Behavior Checklist and Youth Self-Report Total Problems, Internalizing, and Externalizing scales, the rate of improvement for youths in the modular condition was significantly better than for those in usual care. On a measure of functional impairment (Brief Impairment Scale), no significant differences were found among the 3 conditions. Analysis of service utilization also showed no significant differences among conditions, with almost half of youths receiving some additional services in the 1st year after beginning treatment, and roughly one third of youths in the 2nd year.

Conclusions: Overall, these results extend prior findings, supporting incremental benefits of MATCH over usual care over a 2-year period.
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http://dx.doi.org/10.1037/a0034200DOI Listing
December 2013

More practice, less preach? the role of supervision processes and therapist characteristics in EBP implementation.

Adm Policy Ment Health 2013 Nov;40(6):518-29

Department of School-Clinical Child Psychology, Ferkauf Graduate School of Psychology, Yeshiva University, Rousso Building, 1300 Morris Park Avenue, Bronx, NY, 10461, USA,

Identifying predictors of evidence-based practice (EBP) use, such as supervision processes and therapist characteristics, may support dissemination. Therapists (N = 57) received training and supervision in EBPs to treat community-based youth (N = 136). Supervision involving modeling and role-play predicted higher overall practice use than supervision involving discussion, and modeling predicted practice use in the next therapy session. No therapist characteristics predicted practice use, but therapist sex and age moderated the supervision and practice use relation. Supervision involving discussion predicted practice use for male therapists only, and modeling and role-play in supervision predicted practice use for older, not younger, therapists.
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http://dx.doi.org/10.1007/s10488-013-0485-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083565PMC
November 2013

Tracking evidence based practice with youth: validity of the MATCH and standard manual consultation records.

J Clin Child Adolesc Psychol 2013 18;42(1):44-55. Epub 2012 Jul 18.

Department of Psychology, University of California, Los Angeles, CA 90095, USA.

This study sought to evaluate the agreement between therapist report and coder observation of therapy practices. The study sampled session data from a community-based, randomized trial of treatment for youth ages 7 to 13. We used therapist report of session content and coverage gathered using formal Consultation Records and developed complimentary records for coders to use when watching or listening to therapy tape. We established initial reliability between coders and then conducted a random, stratified, and comprehensive sample of sessions across youth (N = 121), therapists (N = 57), conditions (MATCH and Standard Manuals), and study sites (Honolulu and Boston) to code and compare with therapist record reports. Intraclass correlation coefficients (ICCs) representing coder versus therapist agreement on manual content delivered ranged from .42 to 1.0 across conditions and problem areas. Analyses revealed marked variability in agreement regarding whether behavioral rehearsals took place (ICCs from -.01 to 1.0) but strong agreement on client comprehension of therapy content and homework assignments. Overall, the findings indicate that therapists can be accurate reporters of the therapeutic practices they deliver, although they may need more support in reporting subtle but valuable aspects of implementation such as types of behavioral rehearsals. Developing means to support accurate reporting is important to developing future clinical feedback methodology applicable to the implementation of evidence-based treatments in the real world.
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http://dx.doi.org/10.1080/15374416.2012.700505DOI Listing
June 2013