11 Works

Data from: Conserved but flexible modularity in the zebrafish skull: implications for craniofacial evolvability

Kevin J. Parsons, Young H. Son, Amelie Crespel, Davide Thambithurai, Shaun Killen, Matthew P. Harris & R. Craig Albertson
Morphological variation is the outward manifestation of development and provides fodder for adaptive evolution. Because of this contingency, evolution is often thought to be biased by developmental processes and functional interactions among structures, which are statistically detectable through forms of covariance among traits. This can take the form of substructures of integrated traits, termed modules, which together comprise patterns of variational modularity. While modularity is essential to an understanding of evolutionary potential, biologists currently have...

Data from: Revisiting protein aggregation as pathogenic in sporadic Parkinson’s and Alzheimer’s diseases

Alberto J. Espay, Joaquin A. Vizcarra, Luca Marsili, Anthony E. Lang, David K. Simon, Aristide Merola, Keith A. Josephs, Alfonso Fasano, Francesca Morgante, Rodolfo Savica, J. Timothy Greenamyre, Franca Cambi, Tritia R. Yamasaki, Caroline M. Tanner, Ziv Gan-Or, Irene Litvan, Ignacio F. Mata, Cyrus P. Zabetian, Patrik Brundin, Hubert H. Fernandez, David G. Standaert, Marcelo A. Kauffman, Michael A. Schwarzschild, S. Pablo Sardi, Todd Sherer … & James B. Leverenz
The gold standard for a definitive diagnosis of Parkinson’s disease (PD) is the pathologic finding of aggregated alpha-synuclein into Lewy bodies and for Alzheimer’s disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinico-pathologic-based nosology is the assumption that pathological protein aggregation at autopsy reflect pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated alpha-synuclein in SNCA gene multiplication...

Data from: Feedback between tissue packing and neurogenesis in the zebrafish neural tube

Tom W. Hiscock, Joel B. Miesfeld, Kishore R. Mosaliganti, Brian A. Link & Sean G. Megason
Balancing the rate of differentiation and proliferation in developing tissues is essential to produce organs of robust size and composition. Although many molecular regulators have been established, how these connect to physical and geometrical aspects of tissue architecture is poorly understood. Here, using high-resolution timelapse imaging, we find that changes to cell geometry associated with dense tissue packing play a significant role in regulating differentiation rate in the zebrafish neural tube. Specifically, progenitors that are...

Data from: First-in-human randomized controlled trial of an oral, replicating Adenovirus 26 vector vaccine for HIV-1

Kathryn E. Stephenson, Michael C. Keefer, Catherine A. Bunce, Doreen Frances, Peter Abbink, Lori F. Maxfield, George H. Neubauer, Joseph Nkolola, Lauren Peter, Christopher Lane, Harriet Park, Carl Verlinde, Angela Lombardo, Christopher Yallop, Menzo Havenga, Patricia Fast, John Treanor & Dan H. Barouch
Background: Live, attenuated viral vectors that express HIV-1 antigens are being investigated as an approach to generating durable immune responses against HIV-1 in humans. We recently developed a replication-competent, highly attenuated Ad26 vector that expresses mosaic HIV-1 Env (rcAd26.MOS1.HIV-Env, “rcAd26”). Here we present the results of a first-in-human, placebo-controlled clinical trial to test the safety, immunogenicity and mucosal shedding of rcAd26 given orally. Methods: Healthy adults were randomly assigned to receive a single oral dose...

Data from: Abnormal CSF amyloid-β42 and tau levels in hip fracture patients without dementia

Esther S. Oh, Kaj Blennow, George E. Bigelow, Sharon K. Inouye, Edward R. Marcantonio, Karin J. Neufeld, Paul B. Rosenberg, Juan C. Troncoso, Nae-Yuh Wang, Henrik Zetterberg, Frederick Sieber, Constantine G. Lyketsos & Frederick E. Sieber
Background: There is strong association of Alzheimer's disease (AD) pathology with gait disorder and falls in older adults without dementia. The goal of the study was to examine the prevalence and severity of AD pathology in older adults without dementia who fall and sustain hip fracture. Methods: Cerebrospinal fluid (CSF) was obtained from 168 hip fracture patients. CSF Aβ42/40 ratio, p-tau, and t-tau measures were dichotomized into normal vs. abnormal, and categorized according to the...

Data from: Circulating cortisol and cognitive and structural brain measures in a middle-aged cohort: the Framingham Heart Study

Justin B. Echouffo-Tcheugui, Sarah C. Conner, Jayandra J. Himali, Pauline Maillard, Charles S. DeCarli, Alexa S. Beiser, Ramachandran S. Vasan & Sudha Seshadri
Objective: To assess the association of early morning serum cortisol with cognitive performance and brain structural integrity in community-dwelling young and middle-aged adults without dementia. Methods: We evaluated dementia-free Framingham Study (Generation 3) participants (mean age 48.5 years; 46.8% men), who underwent cognitive testing for memory, abstract reasoning, visual perception, attention, and executive function (n= 2231), and brain MRI (n=2018) to assess total white matter, lobar gray matter, and white matter hyperintensity volumes and fractional...

Data from: Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline

Andreea M. Rawlings, Stephen P. Juraschek, Gerardo Heiss, Tim Hughes, Michelle L. Meyer, Elizabeth Selvin, A. Richey Sharrett, B. Gwen Windham & Rebecca F. Gottesman
Objective: To examine associations between orthostatic hypotension (OH) with dementia and long-term cognitive decline, and update previously published results in the same cohort for stroke with an additional 16 years of follow-up. Methods: We analyzed data from 11709 participants without a history of coronary heart disease or stroke who attended the baseline exam (1987-1989) of the prospective Atherosclerosis Risk in Communities (ARIC) study. OH was defined as a drop in systolic blood pressure (BP) of...

Data from: ATRX promotes maintenance of herpes simplex virus heterochromatin during chromatin stress

Joseph M Cabral, Hyung Suk Oh & David M Knipe
The mechanisms by which mammalian cells recognize and epigenetically restrict viral DNA are not well defined. We used herpes simplex virus with bioorthogonally labeled genomes to detect host factors recruited to viral DNA shortly after its nuclear entry and found that the cellular IFI16, PML, and ATRX proteins colocalized with viral DNA by 15 min post infection. HSV-1 infection of ATRX-depleted fibroblasts resulted in elevated viral mRNA and accelerated viral DNA accumulation. Despite the early...

Data from: Association between aspirin dose and subarachnoid hemorrhage from saccular aneurysms: a case-control study

Anil Can, Robert F. Rudy, Victor M. Castro, Sheng Yu, Dmitriy Dligach, Sean Finan, Vivian Gainer, Nancy A. Shadick, Guergana Savova, Shawn Murphy, Tianxi Cai, Scott T. Weiss & Rose Du
Objective: We aimed to determine the association between ruptured saccular aneurysms and aspirin use/aspirin dose. Methods: 4,701 patients who were diagnosed at the Massachusetts General Hospital and Brigham and Women’s Hospital between 1990 and 2016 with 6,411 unruptured and ruptured saccular intracranial aneurysms were evaluated. Univariable and multivariable logistic regression analyses were performed to determine the association between aSAH and aspirin use, including aspirin dose. Inverse probability weighting using propensity scores was used to adjust...

Data from: Immune checkpoint inhibitor–related myositis and myocarditis in patients with cancer

Mehdi Touat, Thierry Maisonobe, Samuel Knauss, Omar Ben Hadj Salem, Baptiste Hervier, Karine Auré, Tali-Anne Szwebel, Nora Kramkimel, Claire Lethrosne, Jean-Frédéric Bruch, Pauline Laly, Jacques Cadranel, Nicolas Weiss, Anthony Béhin, Yves Allenbach, Olivier Benveniste, Timothée Lenglet, Dimitri Psimaras, Werner Stenzel & Sarah Léonard-Louis
Objective: To report the clinicopathological features and outcome of myositis in patients treated with immune checkpoint inhibitors (irMyositis). Methods: We retrospectively analyzed patients diagnosed with irMyositis in tertiary centers in Paris, France, and Berlin, Germany, from January 2015, to July 2017. Main outcomes were clinical manifestations and muscle histology, which included MHC-I, C5b-9, CD3, CD4, CD8, CD20, CD68, PD-1, PD-L1 and PD-L2 immunohistochemical stains. Results: Ten patients with metastatic cancer were included; median age was...

Data from: Temperature drives Zika virus transmission: evidence from empirical and mathematical models

Blanka Tesla, Leah Demakovsky, Erin Mordecai, Sadie Ryan, Matthew Bonds, Calistus Ngonghala, Melinda Brindley & Courtney Murdock
Temperature is a strong driver of vector-borne disease transmission. Yet, for emerging arboviruses we lack fundamental knowledge on the relationship between transmission and temperature. Current models rely on the untested assumption that Zika virus responds similarly to dengue virus, potentially limiting our ability to accurately predict the spread of Zika. We conducted experiments to estimate the thermal performance of Zika virus (ZIKV) in field-derived Aedes aegypti across eight constant temperatures. We observed strong, unimodal effects...

Registration Year

  • 2018

Resource Types

  • Dataset


  • Harvard Medical School
  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Charité
  • University of Massachusetts Amherst
  • University of Alabama at Birmingham
  • Boston Children's Hospital
  • Stanford University
  • VA Puget Sound Health Care System
  • Hôpital Cochin