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https://www.readbyqxmd.com/read/28167275/single-amino-acid-fingerprinting-of-the-human-antibody-repertoire-with-high-density-peptide-arrays
#1
Laura K Weber, Andrea Palermo, Jonas Kügler, Olivier Armant, Awale Isse, Simone Rentschler, Thomas Jaenisch, Jürgen Hubbuch, Stefan Dübel, Alexander Nesterov-Mueller, Frank Breitling, Felix F Loeffler
The antibody species that patrol in a patient's blood are an invaluable part of the immune system. While most of them shield us from life-threatening infections, some of them do harm in autoimmune diseases. If we knew exactly all the antigens that elicited all the antibody species within a group of patients, we could learn which ones correlate with immune protection, are irrelevant, or do harm. Here, we demonstrate an approach to this question: First, we use a plethora of phage-displayed peptides to identify many different serum antibody binding peptides...
February 3, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28132741/respiratory-muscle-training-improves-chemoreflex-response-heart-rate-variability-and-respiratory-mechanics-in-rats-with-heart-failure
#2
Rodrigo B Jaenisch, Edson Quagliotto, Chalyne Chechi, Leonardo Calegari, Fernando Dos Santos, Audrey Borghi-Silva, Pedro Dal Lago
BACKGROUND: The aim of the present report was to evaluate respiratory muscle training (RMT) effects on hemodynamic function, chemoreflex response, heart rate variability, and respiratory mechanics in rats with heart failure (HF rats). METHODS: Wistar rats were divided into 4 groups: sedentary-sham (Sed-Sham, n = 8), respiratory muscle trained-sham (RMT-Sham, n = 8), sedentary-HF (Sed-HF, n = 8) and respiratory muscle trained-HF (RMT-HF, n = 8). Animals were submitted to an RMT protocol performed 30 minutes per day, 5 days per week for 6 weeks, whereas the sedentary animals did not exercise...
November 11, 2016: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28074830/tet1-in-nucleus-accumbens-opposes-depression-and-anxiety-like-behaviors
#3
Jian Feng, Catherine J Pena, Immanuel Purushothaman, Olivia Engmann, Deena Walker, Amber N Brown, Orna Issler, Marie Doyle, Eileen Harrigan, Ezekiell Mouzon, Vincent Vialou, Li Shen, Meelad M Dawlaty, Rudolf Jaenisch, Eric J Nestler
Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here, we examined a possible role for the DNA dioxygenase, ten eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28041895/induction-of-expansion-and-folding-in-human-cerebral-organoids
#4
Yun Li, Julien Muffat, Attya Omer, Irene Bosch, Madeline A Lancaster, Mriganka Sur, Lee Gehrke, Juergen A Knoblich, Rudolf Jaenisch
An expansion of the cerebral neocortex is thought to be the foundation for the unique intellectual abilities of humans. It has been suggested that an increase in the proliferative potential of neural progenitors (NPs) underlies the expansion of the cortex and its convoluted appearance. Here we show that increasing NP proliferation induces expansion and folding in an in vitro model of human corticogenesis. Deletion of PTEN stimulates proliferation and generates significantly larger and substantially folded cerebral organoids...
December 20, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28028355/from-blood-to-breath-new-horizons-for-esophageal-cancer-biomarkers
#5
EDITORIAL
Roger Yazbeck, Simone E Jaenisch, David I Watson
Esophageal cancer is a lethal cancer encompassing adenocarcinoma and squamous cell carcinoma sub-types. The global incidence of esophageal cancer is increasing world-wide, associated with the increased prevalence of associated risk factors. The asymptomatic nature of disease often leads to late diagnosis and five-year survival rates of less than 15%. Current diagnostic tools are restricted to invasive and costly endoscopy and biopsy for histopathology. Minimally and non-invasive biomarkers of esophageal cancer are needed to facilitate earlier detection and better clinical management of patients...
December 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27989770/human-naive-pluripotent-stem-cells-model-x-chromosome-dampening-and-x-inactivation
#6
Anna Sahakyan, Rachel Kim, Constantinos Chronis, Shan Sabri, Giancarlo Bonora, Thorold W Theunissen, Edward Kuoy, Justin Langerman, Amander T Clark, Rudolf Jaenisch, Kathrin Plath
Naive human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X chromosome state has remained unresolved. Here, we show that the inactive X chromosome (Xi) of primed hESCs was reactivated in naive culture conditions. Like cells of the blastocyst, the resulting naive cells contained two active X chromosomes with XIST expression and chromosome-wide transcriptional dampening and initiated XIST-mediated X inactivation upon differentiation. Both establishment of and exit from the naive state (differentiation) happened via an XIST-negative XaXa intermediate...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/27905428/stem-cells-and-interspecies-chimaeras
#7
Jun Wu, Henry T Greely, Rudolf Jaenisch, Hiromitsu Nakauchi, Janet Rossant, Juan Carlos Izpisua Belmonte
Chimaeras are both monsters of the ancient imagination and a long-established research tool. Recent advances, particularly those dealing with the identification and generation of various kinds of stem cells, have broadened the repertoire and utility of mammalian interspecies chimaeras and carved out new paths towards understanding fundamental biology as well as potential clinical applications.
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27803317/jointly-reduced-inhibition-and-excitation-underlies-circuit-wide-changes-in-cortical-processing-in-rett-syndrome
#8
Abhishek Banerjee, Rajeev V Rikhye, Vincent Breton-Provencher, Xin Tang, Chenchen Li, Keji Li, Caroline A Runyan, Zhanyan Fu, Rudolf Jaenisch, Mriganka Sur
Rett syndrome (RTT) arises from loss-of-function mutations in methyl-CpG binding protein 2 gene (Mecp2), but fundamental aspects of its physiological mechanisms are unresolved. Here, by whole-cell recording of synaptic responses in MeCP2 mutant mice in vivo, we show that visually driven excitatory and inhibitory conductances are both reduced in cortical pyramidal neurons. The excitation-to-inhibition (E/I) ratio is increased in amplitude and prolonged in time course. These changes predict circuit-wide reductions in response reliability and selectivity of pyramidal neurons to visual stimuli, as confirmed by two-photon imaging...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27768957/cns-disease-models-with-human-pluripotent-stem-cells-in-the-crispr-age
#9
REVIEW
Julien Muffat, Yun Li, Rudolf Jaenisch
In vitro differentiation of human pluripotent stem cells provides a systematic platform to investigate the physiological development and function of the human nervous system, as well as the etiology and consequence when these processes go awry. Recent development in three-dimensional (3D) organotypic culture systems allows modeling of the complex structure formation of the human CNS, and the intricate interactions between various resident neuronal and glial cell types. Combined with an ever-expanding genome editing and regulation toolkit such as CRISPR/Cas9, it is now a possibility to study human neurological disease in the relevant molecular, cellular and anatomical context...
December 2016: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/27668937/efficient-derivation-of-microglia-like-cells-from-human-pluripotent-stem-cells
#10
Julien Muffat, Yun Li, Bingbing Yuan, Maisam Mitalipova, Attya Omer, Sean Corcoran, Grisilda Bakiasi, Li-Huei Tsai, Patrick Aubourg, Richard M Ransohoff, Rudolf Jaenisch
Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages that have been recognized to have a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human (h) embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions...
November 2016: Nature Medicine
https://www.readbyqxmd.com/read/27662091/editing-dna-methylation-in-the-mammalian-genome
#11
X Shawn Liu, Hao Wu, Xiong Ji, Yonatan Stelzer, Xuebing Wu, Szymon Czauderna, Jian Shu, Daniel Dadon, Richard A Young, Rudolf Jaenisch
Mammalian DNA methylation is a critical epigenetic mechanism orchestrating gene expression networks in many biological processes. However, investigation of the functions of specific methylation events remains challenging. Here, we demonstrate that fusion of Tet1 or Dnmt3a with a catalytically inactive Cas9 (dCas9) enables targeted DNA methylation editing. Targeting of the dCas9-Tet1 or -Dnmt3a fusion protein to methylated or unmethylated promoter sequences caused activation or silencing, respectively, of an endogenous reporter...
September 22, 2016: Cell
https://www.readbyqxmd.com/read/27559725/dengue-in-the-context-of-the-integrated-management-of-childhood-illness
#12
Jacqueline Deen, Martin W Weber, Thomas Jaenisch
No abstract text is available yet for this article.
August 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27424783/molecular-criteria-for-defining-the-naive-human-pluripotent-state
#13
Thorold W Theunissen, Marc Friedli, Yupeng He, Evarist Planet, Ryan C O'Neil, Styliani Markoulaki, Julien Pontis, Haoyi Wang, Alexandra Iouranova, Michaël Imbeault, Julien Duc, Malkiel A Cohen, Katherine J Wert, Rosa Castanon, Zhuzhu Zhang, Yanmei Huang, Joseph R Nery, Jesse Drotar, Tenzin Lungjangwa, Didier Trono, Joseph R Ecker, Rudolf Jaenisch
Recent studies have aimed to convert cultured human pluripotent cells to a naive state, but it remains unclear to what extent the resulting cells recapitulate in vivo naive pluripotency. Here we propose a set of molecular criteria for evaluating the naive human pluripotent state by comparing it to the human embryo. We show that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. We also show that induction of the naive state is accompanied by genome-wide DNA hypomethylation, which is reversible except at imprinted genes, and that the X chromosome status resembles that of the human preimplantation embryo...
October 6, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27317898/a-conversation-with-rudolf-jaenisch
#14
Parker B Antin
No abstract text is available yet for this article.
July 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/27188341/reduced-tonic-inhibition-after-stroke-promotes-motor-performance-and-epileptic-seizures
#15
Nadine Jaenisch, Lutz Liebmann, Madlen Guenther, Christian A Hübner, Christiane Frahm, Otto W Witte
Stroke survivors often recover from motor deficits, either spontaneously or with the support of rehabilitative training. Since tonic GABAergic inhibition controls network excitability, it may be involved in recovery. Middle cerebral artery occlusion in rodents reduces tonic GABAergic inhibition in the structurally intact motor cortex (M1). Transcript and protein abundance of the extrasynaptic GABAA-receptor complex α4β3δ are concurrently reduced (δ-GABAARs). In vivo and in vitro analyses show that stroke-induced glutamate release activates NMDA receptors, thereby reducing KCC2 transporters and down-regulates δ-GABAARs...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27152442/induced-pluripotent-stem-cells-meet-genome-editing
#16
REVIEW
Dirk Hockemeyer, Rudolf Jaenisch
It is extremely rare for a single experiment to be so impactful and timely that it shapes and forecasts the experiments of the next decade. Here, we review how two such experiments-the generation of human induced pluripotent stem cells (iPSCs) and the development of CRISPR/Cas9 technology-have fundamentally reshaped our approach to biomedical research, stem cell biology, and human genetics. We will also highlight the previous knowledge that iPSC and CRISPR/Cas9 technologies were built on as this groundwork demonstrated the need for solutions and the benefits that these technologies provided and set the stage for their success...
May 5, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27137347/in-vitro-development-and-validation-of-a-non-invasive-13-c-stable-isotope-assay-for-ornithine-decarboxylase
#17
Simone Jaenisch, Michelle Squire, Ross Butler, Roger Yazbeck
Oesophageal cancer is a significant cause of cancer related mortality, with increasing incidence worldwide. Ornithine decarboxylase (ODC) is an enzyme involved in polyamine synthesis and cellular proliferation, and ODC expression and activity has been implicated as a prognostic marker of oesophageal cancer. This study aimed to develop and optimise an in vitro (13)C-stable isotope assay for ODC activity as a non-invasive marker of oesophageal cancer. Experiments were performed in triplicate (n  =  3/group/cell line) using Caco2, HeLa, Flo-1, OE33, TE7 and OE21 cell lines (colorectal, cervical, oesophageal adenocarcinoma and oesophageal squamous carcinoma respectively)...
May 3, 2016: Journal of Breath Research
https://www.readbyqxmd.com/read/27096366/parkinson-associated-risk-variant-in-distal-enhancer-of-%C3%AE-synuclein-modulates-target-gene-expression
#18
Frank Soldner, Yonatan Stelzer, Chikdu S Shivalila, Brian J Abraham, Jeanne C Latourelle, M Inmaculada Barrasa, Johanna Goldmann, Richard H Myers, Richard A Young, Rudolf Jaenisch
Genome-wide association studies (GWAS) have identified numerous genetic variants associated with complex diseases, but mechanistic insights are impeded by a lack of understanding of how specific risk variants functionally contribute to the underlying pathogenesis. It has been proposed that cis-acting effects of non-coding risk variants on gene expression are a major factor for phenotypic variation of complex traits and disease susceptibility. Recent genome-scale epigenetic studies have highlighted the enrichment of GWAS-identified variants in regulatory DNA elements of disease-relevant cell types...
May 5, 2016: Nature
https://www.readbyqxmd.com/read/27090089/mapping-global-environmental-suitability-for-zika-virus
#19
Jane P Messina, Moritz Ug Kraemer, Oliver J Brady, David M Pigott, Freya M Shearer, Daniel J Weiss, Nick Golding, Corrine W Ruktanonchai, Peter W Gething, Emily Cohn, John S Brownstein, Kamran Khan, Andrew J Tatem, Thomas Jaenisch, Christopher Jl Murray, Fatima Marinho, Thomas W Scott, Simon I Hay
Zika virus was discovered in Uganda in 1947 and is transmitted by Aedes mosquitoes, which also act as vectors for dengue and chikungunya viruses throughout much of the tropical world. In 2007, an outbreak in the Federated States of Micronesia sparked public health concern. In 2013, the virus began to spread across other parts of Oceania and in 2015, a large outbreak in Latin America began in Brazil. Possible associations with microcephaly and Guillain-Barré syndrome observed in this outbreak have raised concerns about continued global spread of Zika virus, prompting its declaration as a Public Health Emergency of International Concern by the World Health Organization...
April 19, 2016: ELife
https://www.readbyqxmd.com/read/27070912/zika-virus-outbreak-in-rio-de-janeiro-brazil-clinical-characterization-epidemiological-and-virological-aspects
#20
Patrícia Brasil, Guilherme Amaral Calvet, André Machado Siqueira, Mayumi Wakimoto, Patrícia Carvalho de Sequeira, Aline Nobre, Marcel de Souza Borges Quintana, Marco Cesar Lima de Mendonça, Otilia Lupi, Rogerio Valls de Souza, Carolina Romero, Heruza Zogbi, Clarisse da Silveira Bressan, Simone Sampaio Alves, Ricardo Lourenço-de-Oliveira, Rita Maria Ribeiro Nogueira, Marilia Sá Carvalho, Ana Maria Bispo de Filippis, Thomas Jaenisch
BACKGROUND: In 2015, Brazil was faced with the cocirculation of three arboviruses of major public health importance. The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between diseases caused by ZIKV, Dengue (DENV) and Chikungunya (CHIKV) and the lack of validated serological assays for ZIKV make accurate diagnosis difficult. METHODOLOGY / PRINCIPAL FINDINGS: The outpatient service for acute febrile illnesses in Fiocruz initiated a syndromic clinical observational study in 2007 to capture unusual presentations of DENV infections...
April 2016: PLoS Neglected Tropical Diseases
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