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Paola Mariela Saba Villarroel, Elif Nurtop, Boris Pastorino, Yelin Roca, Jan Felix Drexler, Pierre Gallian, Thomas Jaenisch, Isabelle Leparc-Goffart, Stéphane Priet, Laetitia Ninove, Xavier de Lamballerie
BACKGROUND: Zika virus (ZIKV), was widely reported in Latin America and has been associated with neuropathologies, as microcephaly, but only few seroprevalence studies have been published to date. Our objective was to determine the seroprevalence amongst Bolivian blood donors and estimate the future potential circulation of the virus. METHODOLOGY: A ZIKV seroprevalence study was conducted between December 2016 and April 2017 in 814 asymptomatic Bolivian volunteer blood donors residing in various eco-environments corresponding to contrasting entomological activities...
March 7, 2018: PLoS Neglected Tropical Diseases
X Shawn Liu, Hao Wu, Marine Krzisch, Xuebing Wu, John Graef, Julien Muffat, Denes Hnisz, Charles H Li, Bingbing Yuan, Chuanyun Xu, Yun Li, Dan Vershkov, Angela Cacace, Richard A Young, Rudolf Jaenisch
Fragile X syndrome (FXS), the most common genetic form of intellectual disability in males, is caused by silencing of the FMR1 gene associated with hypermethylation of the CGG expansion mutation in the 5' UTR of FMR1 in FXS patients. Here, we applied recently developed DNA methylation editing tools to reverse this hypermethylation event. Targeted demethylation of the CGG expansion by dCas9-Tet1/single guide RNA (sgRNA) switched the heterochromatin status of the upstream FMR1 promoter to an active chromatin state, restoring a persistent expression of FMR1 in FXS iPSCs...
February 8, 2018: Cell
Abraham S Weintraub, Charles H Li, Alicia V Zamudio, Alla A Sigova, Nancy M Hannett, Daniel S Day, Brian J Abraham, Malkiel A Cohen, Behnam Nabet, Dennis L Buckley, Yang Eric Guo, Denes Hnisz, Rudolf Jaenisch, James E Bradner, Nathanael S Gray, Richard A Young
There is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory elements depend on CTCF-CTCF interactions, but most enhancer-promoter interactions do not employ this structural protein. Here, we show that the ubiquitously expressed transcription factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner analogous to DNA interactions mediated by CTCF...
December 14, 2017: Cell
Chang-Ki Oh, Abdullah Sultan, Joseph Platzer, Nima Dolatabadi, Frank Soldner, Daniel B McClatchy, Jolene K Diedrich, John R Yates, Rajesh Ambasudhan, Tomohiro Nakamura, Rudolf Jaenisch, Stuart A Lipton
Mutations in PARK6 (PINK1) and PARK2 (Parkin) are linked to rare familial cases of Parkinson's disease (PD). Mutations in these genes result in pathological dysregulation of mitophagy, contributing to neurodegeneration. Here, we report that environmental factors causing a specific posttranslational modification on PINK1 can mimic these genetic mutations. We describe a molecular mechanism for impairment of mitophagy via formation of S-nitrosylated PINK1 (SNO-PINK1). Mitochondrial insults simulating age- or environmental-related stress lead to increased SNO-PINK1, inhibiting its kinase activity...
November 21, 2017: Cell Reports
Eduardo Martins Netto, Andres Moreira-Soto, Celia Pedroso, Christoph Höser, Sebastian Funk, Adam J Kucharski, Alexandra Rockstroh, Beate M Kümmerer, Gilmara Souza Sampaio, Estela Luz, Sara Nunes Vaz, Juarez Pereira Dias, Fernanda Anjos Bastos, Renata Cabral, Thomas Kistemann, Sebastian Ulbert, Xavier de Lamballerie, Thomas Jaenisch, Oliver J Brady, Christian Drosten, Manoel Sarno, Carlos Brites, Jan Felix Drexler
During 2015 to 2016, Brazil reported more Zika virus (ZIKV) cases than any other country, yet population exposure remains unknown. Serological studies of ZIKV are hampered by cross-reactive immune responses against heterologous viruses. We conducted serosurveys for ZIKV, dengue virus (DENV), and Chikungunya virus (CHIKV) in 633 individuals prospectively sampled during 2015 to 2016, including microcephaly and non-microcephaly pregnancies, HIV-infected patients, tuberculosis patients, and university staff in Salvador in northeastern Brazil using enzyme-linked immunosorbent assays (ELISAs) and plaque reduction neutralization tests...
November 14, 2017: MBio
Kamran Harati, Anais Jaenisch, Björn Behr, Ole Goertz, Ali Harati, Tobias Hirsch, Ingo Stricker, Marcus Lehnhardt, Adrien Daigeler
The treatment of aggressive fibromatosis poses a therapeutic challenge in an interdisciplinary setting. The extent of surgical resection is still discussed controversially. The present retrospective analysis aimed to determine prognostic factors leading to recurrence. Between 2000 and 2014, 114 patients with aggressive fibromatosis were treated surgically at BG-University Hospital Bergmannsheil (Bochum, Germany). Univariate and multivariate analyses were restricted to 90 participants with information available on surgical margins at the initial procedure...
November 2017: Oncology Letters
Tereza Magalhaes, Cynthia Braga, Marli T Cordeiro, Andre L S Oliveira, Priscila M S Castanha, Ana Paula R Maciel, Nathalia M L Amancio, Pollyanne N Gouveia, Valter J Peixoto-da-Silva, Thaciana F L Peixoto, Helena Britto, Priscilla V Lima, Andreza R S Lima, Kerstin D Rosenberger, Thomas Jaenisch, Ernesto T A Marques
BACKGROUND: Several arboviruses, including dengue virus (DENV), Zika virus (ZIKV) and chikungunya virus (CHIKV), transmitted by Aedes mosquitoes, circulate in northeast Brazil. Diseases caused by these viruses are of great public health relevance, however, their epidemiological features in areas where the three viruses co-circulate are scarce. Here, we present analyses of molecular and serological diagnostics in a prospective study of acute febrile patients recruited from May 2015 to May 2016 in Recife, Brazil...
November 2017: PLoS Neglected Tropical Diseases
Stefan Semrau, Johanna E Goldmann, Magali Soumillon, Tarjei S Mikkelsen, Rudolf Jaenisch, Alexander van Oudenaarden
Gene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measure the gene expression dynamics of retinoic acid driven mESC differentiation from pluripotency to lineage commitment, using an unbiased single-cell transcriptomics approach. We find that the exit from pluripotency marks the start of a lineage transition as well as a transient phase of increased susceptibility to lineage specifying signals...
October 23, 2017: Nature Communications
Giovanna Tedesco Barcelos, Douglas Dalcin Rossato, Júlia Luiza Perini, Lucas Pereira Pinheiro, Carol Carvalho, Rodrigo Boemo Jaenisch, Cláudia Ramos Rhoden, Pedro Dal Lago, Ramiro Barcos Nunes
OBJECTIVE: Chronic heart failure (CHF) is related with exercise intolerance and impaired nitric oxide (NO) production, which can lead to several functional capacity alterations. Considering the possible superiority of aerobic interval training compared to continuous training and the capacity of l-arginine to restore the NO pathway, the aim of the present study was to investigate whether these treatments are beneficial to exercise capacity, muscle mass preservation and hemodynamic, inflammatory and oxidative stress parameters in CHF rats...
November 2017: Metabolism: Clinical and Experimental
Duanqing Pei, David W Beier, Ephrat Levy-Lahad, Gary Marchant, Janet Rossant, Juan Carlos Izpisua Belmonte, Robin Lovell-Badge, Rudolf Jaenisch, Alta Charo, David Baltimore
A recent National Academies report articulates a path forward for research, ethics, and governance of clinical applications involving genome editing. In light of recent human embryo editing developments, scientists and stakeholders from all nations should cooperate to take advantage of this historic opportunity for medicine and also basic human biology.
October 5, 2017: Cell Stem Cell
Arigela Harikumar, Raghu Ram Edupuganti, Matan Sorek, Gajendra Kumar Azad, Styliani Markoulaki, Petra Sehnalová, Soňa Legartová, Eva Bártová, Shlomit Farkash-Amar, Rudolf Jaenisch, Uri Alon, Eran Meshorer
Embryonic stem cells (ESCs), with their dual capacity to self-renew and differentiate, are commonly used to study differentiation, epigenetic regulation, lineage choices, and more. Using non-directed retroviral integration of a YFP/Cherry exon into mouse ESCs, we generated a library of over 200 endogenously tagged fluorescent fusion proteins and present several proof-of-concept applications of this library. We show the utility of this library to track proteins in living cells; screen for pluripotency-related factors; identify heterogeneously expressing proteins; measure the dynamics of endogenously labeled proteins; track proteins recruited to sites of DNA damage; pull down tagged fluorescent fusion proteins using anti-Cherry antibodies; and test for interaction partners...
October 10, 2017: Stem Cell Reports
Raghu Ram Edupuganti, Arigela Harikumar, Yair Aaronson, Alva Biran, Badi Sri Sailaja, Malka Nissim-Rafinia, Gajendra Kumar Azad, Malkiel A Cohen, Jung Eun Park, Chikdu S Shivalila, Styliani Markoulaki, Siu Kwan Sze, Rudolf Jaenisch, Eran Meshorer
Embryonic stem cells (ESCs) are regulated by pluripotency-related transcription factors in concert with chromatin regulators. To identify additional stem cell regulators, we screened a library of endogenously labeled fluorescent fusion proteins in mouse ESCs for fluorescence loss during differentiation. We identified SET, which displayed a rapid isoform shift during early differentiation from the predominant isoform in ESCs, SETα, to the primary isoform in differentiated cells, SETβ, through alternative promoters...
October 10, 2017: Stem Cell Reports
Roger Yazbeck, Simone E Jaenisch, Catherine A Abbott
The importance of the dipeptidyl peptidase 4 (DPP4) gene family in regulating critical biochemical pathways continues to emerge. The two most well-studied members of the family, DPP4 and fibroblast activation protein (FAP), have been investigated both as therapeutic targets for disease and as diagnostic biomarkers. The interest in DPP4 and FAP as potential disease biomarkers has been driven primarily by observations of altered expression profiles in inflammatory diseases and cancer. Furthermore, the stability and persistence of soluble DPP4 and FAP in the serum make them attractive candidate serology markers...
June 16, 2017: Protoplasma
Daiane Voss-Rech, Iara Maria Trevisol, Liana Brentano, Virgínia Santiago Silva, Raquel Rebelatto, Fátima Regina Ferreira Jaenisch, Cintia Hiromi Okino, Marcos Antonio Zanella Mores, Arlei Coldebella, Sônia de Avila Botton, Clarissa Silveira Luiz Vaz
The microbiological risk of recycled litter depends on the efficacy of the management system applied to inactivate residual microorganisms and preserve the health of the successive broiler flock. This study aimed to assess the viability and infectivity of the Newcastle Disease Virus (NDV), Infectious Bursal Disease Virus (IBDV) and Salmonella Heidelberg in recycled litter exposed to different treatments. The litter was contaminated with microorganisms and submitted to the treatments (T): T1: shallow fermentation; T2: quicklime (calcium oxide); T3: shallow fermentation followed by addition of quicklime; T4: no treatment...
May 2017: Veterinary Microbiology
Mary C Wildermuth, Michael A Steinwand, Amanda G McRae, Johan Jaenisch, Divya Chandran
Diverse plant biotrophs that establish a sustained site of nutrient acquisition induce localized host endoreduplication. Endoreduplication is a process by which cells successively replicate their genomes without mitosis, resulting in an increase in nuclear DNA ploidy. Elevated ploidy is associated with enhanced cell size, metabolic capacity, and the capacity to differentiate. Localized host endoreduplication induced by adapted plant biotrophs promotes biotroph colonization, development, and/or proliferation...
August 4, 2017: Annual Review of Phytopathology
James Whitehorn, Duong Thi Hue Kien, Nguyen Than Ha Quyen, Bridget Wills, Nguyen Van Vinh Chau, Dong Thi Hoai Tam, Nguyen Minh Tuan, Thomas Jaenisch, Martin Hibberd, Chiea Chuen Khor, Cameron P Simmons
BACKGROUND: A previous genome-wide association study identified 2 susceptibility loci for severe dengue at MICB rs3132468 and PLCE1 rs3740360 and further work showed these mutations to be also associated with less severe clinical presentations. The aim of this study was to determine if these specific loci were associated with laboratory features of dengue that correlate with clinical severity with the aim of elucidating the functional basis of these genetic variants. METHODS: This was a case-only analysis of laboratory-confirmed dengue patients obtained from 2 prospective cohort studies and 1 randomised clinical trial in Vietnam (Trial registration: ISRCTN ISRCTN03147572...
June 9, 2017: BMC Infectious Diseases
N R Faria, J Quick, I M Claro, J Thézé, J G de Jesus, M Giovanetti, M U G Kraemer, S C Hill, A Black, A C da Costa, L C Franco, S P Silva, C-H Wu, J Raghwani, S Cauchemez, L du Plessis, M P Verotti, W K de Oliveira, E H Carmo, G E Coelho, A C F S Santelli, L C Vinhal, C M Henriques, J T Simpson, M Loose, K G Andersen, N D Grubaugh, S Somasekar, C Y Chiu, J E Muñoz-Medina, C R Gonzalez-Bonilla, C F Arias, L L Lewis-Ximenez, S A Baylis, A O Chieppe, S F Aguiar, C A Fernandes, P S Lemos, B L S Nascimento, H A O Monteiro, I C Siqueira, M G de Queiroz, T R de Souza, J F Bezerra, M R Lemos, G F Pereira, D Loudal, L C Moura, R Dhalia, R F França, T Magalhães, E T Marques, T Jaenisch, G L Wallau, M C de Lima, V Nascimento, E M de Cerqueira, M M de Lima, D L Mascarenhas, J P Moura Neto, A S Levin, T R Tozetto-Mendoza, S N Fonseca, M C Mendes-Correa, F P Milagres, A Segurado, E C Holmes, A Rambaut, T Bedford, M R T Nunes, E C Sabino, L C J Alcantara, N J Loman, O G Pybus
Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly...
June 15, 2017: Nature
Shane A Phillips, Daniela Kuguimoto Andaku, Renata Gonçalves Mendes, Flávia Rossi Caruso, Ramona Cabiddu, Rodrigo Boemo Jaenisch, Ross Arena, Audrey Borghi-Silva
The endothelium plays an important role in maintaining vascular homeostasis and regulating blood vessel function. Endothelial function is considered an independent predictor for risk of future cardiovascular events in cardiovascular and non-cardiovascular patients, as well as a predictor for postoperative complications in cardiovascular surgery patients. Brachial artery flow-mediated dilation by high-resolution ultrasound is widely used to evaluate endothelium-dependent vasodilation, which is mainly mediated by nitric oxide release...
March 2017: Brazilian Journal of Cardiovascular Surgery
Rodrigo Boemo Jaenisch, Mariane Bertagnolli, Audrey Borghi-Silva, Ross Arena, Pedro Dal Lago
INTRODUCTION: Enhanced respiratory muscle strength in patients with heart failure positively alters the clinical trajectory of heart failure. In an experimental model, respiratory muscle training in rats with heart failure has been shown to improve cardiopulmonary function through mechanisms yet to be entirely elucidated. OBJECTIVE: The present report aimed to evaluate the respiratory muscle training effects in diaphragm citrate synthase activity and hemodynamic function in rats with heart failure...
March 2017: Brazilian Journal of Cardiovascular Surgery
Nunya Chotiwan, Connie D Brewster, Tereza Magalhaes, James Weger-Lucarelli, Nisha K Duggal, Claudia Rückert, Chilinh Nguyen, Selene M Garcia Luna, Joseph R Fauver, Barb Andre, Meg Gray, William C Black, Rebekah C Kading, Gregory D Ebel, Guillermina Kuan, Angel Balmaseda, Thomas Jaenisch, Ernesto T A Marques, Aaron C Brault, Eva Harris, Brian D Foy, Sandra L Quackenbush, Rushika Perera, Joel Rovnak
Understanding the dynamics of Zika virus transmission and formulating rational strategies for its control require precise diagnostic tools that are also appropriate for resource-poor environments. We have developed a rapid and sensitive loop-mediated isothermal amplification (LAMP) assay that distinguishes Zika viruses of Asian and African lineages. The assay does not detect chikungunya virus or flaviviruses such as dengue, yellow fever, or West Nile viruses. The assay conditions allowed direct detection of Zika virus RNA in cultured infected cells; in mosquitoes; in virus-spiked samples of human blood, plasma, saliva, urine, and semen; and in infected patient serum, plasma, and semen samples without the need for RNA isolation or reverse transcription...
May 3, 2017: Science Translational Medicine
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