Publications by authors named "Nico Weber"

7 Publications

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The Endometrial Transcription Landscape of MRKH Syndrome.

Front Cell Dev Biol 2020 24;8:572281. Epub 2020 Sep 24.

Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany.

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (OMIM 277000) is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. While genetic causes have been identified for a small subset of patients and epigenetic mechanisms presumably contribute to the pathogenic unfolding, too, the etiology of the syndrome has remained largely enigmatic. A comprehensive understanding of gene activity in the context of the disease is crucial to identify etiological components and their potential interplay. So far, this understanding is lacking, primarily due to the scarcity of samples and suitable tissue. In order to close this gap, we profiled endometrial tissue of uterus rudiments in a large cohort of MRKH patients using RNA-seq and thereby provide a genome-wide view on the altered transcription landscape of the MRKH syndrome. Differential and co-expression analyses of the data identified cellular processes and candidate genes that converge on a core network of interconnected regulators that emerge as pivotal for the perturbed expression space. With these results and browsable access to the rich data through an online tool we seek to accelerate research to unravel the underlying biology of the syndrome.
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http://dx.doi.org/10.3389/fcell.2020.572281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542331PMC
September 2020

Glucocorticoid administration restores salience network activity in patients with spider phobia.

Depress Anxiety 2018 10 12;35(10):925-934. Epub 2018 Aug 12.

Division of Systems Neuroscience of Psychopathology, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.

Background: Glucocorticoids reduce phobic fear in patients with anxiety disorders. Although the neurobiology of anxiety disorders is not fully understood, convergent structural and functional neuroimaging studies have identified abnormalities in various brain regions, including those in the salience network (SN) and default mode network (DMN). Here, we examine the effects of glucocorticoid administration on SN and DMN activity during the processing of phobic stimuli.

Methods: We use functional magnetic resonance imaging to record brain activity in 24 female patients with spider phobia who were administered either 20 mg of cortisol or placebo while viewing pictures of spiders. Fourteen healthy female participants were tested with the same task but without substance administration. Independent component analysis (ICA) performed during stimulus encoding identified the SN and DMN as exhibiting synchronized activation in diverse brain regions; thus, we examined the effects of cortisol on these networks. Furthermore, participants had to rate their level of fear at various time points.

Results: Glucocorticoids reduced phobic fear in patients with spider phobia. The ICA performed during stimulus encoding revealed that activity in the SN and DMN was reduced in placebo-treated patients versus healthy controls. Brain activity in the SN, but not the DMN, was altered in cortisol- versus placebo-treated patients to a level that was similar to that observed in healthy controls.

Conclusions: Activity in both the SN and DMN was reduced in patients with spider phobia. Cortisol administration altered the SN activity to a level that was comparable to that found in healthy controls. This alteration in SN activity might reflect the fear-reducing effects of glucocorticoids in phobia.
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http://dx.doi.org/10.1002/da.22806DOI Listing
October 2018

VHL-dependent alterations in the secretome of renal cell carcinoma: Association with immune cell response?

Oncotarget 2015 Dec;6(41):43420-37

Martin Luther University Halle-Wittenberg, Institute of Medical Immunology, 06112 Halle (Saale), Germany.

Secreted proteins could modulate the interaction between tumor, stroma and immune cells within the tumor microenvironment thereby mounting an immunosuppressive tumor microenvironment. In order to determine the secretome-mediated, von Hippel Lindau (VHL)-regulated cross-talk between tumor cells and T lymphocytes peripheral blood mononuclear cells (PBMC) from healthy donors were either cultured in conditioned media obtained from normoxic and hypoxic human VHL-deficient renal cell carcinoma (RCC) cell line (786-0VHL-) and its wild type (wt) VHL-transfected counterpart (786-0VHL+) or directly co-cultured with both cell lines. An increased T cell proliferation was detected in the presence of 786-0VHL+-conditioned medium. By applying a quantitative proteomic-based approach using differential gel electrophoresis followed by mass spectrometry fourteen proteins were identified to be differentially expressed within the secretome of 786-0VHL- cells when compared to that of 786-0VHL+ cells. All proteins identified were involved in multiple tumor-associated biological functions including immune responses. Functional studies on manganese superoxide dismutase 2 (MnSOD2) demonstrated that it was a regulator of T cell activation-induced oxidative signaling and cell death. Direct effects of soluble MnSOD2 on the growth properties and interleukin 2 (IL-2) secretion of T cells could be demonstrated underlining the critical role of extracellular MnSOD2 levels for T cell proliferation and activation.
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http://dx.doi.org/10.18632/oncotarget.5560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791241PMC
December 2015

Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis.

Nature 2014 Oct 20;514(7523):494-7. Epub 2014 Aug 20.

1] Department of Archaeological Sciences, University of Tübingen, Ruemelinstraße 23, 72070 Tübingen, Germany [2] Senckenberg Centre for Human Evolution and Palaeoenvironment, University of Tübingen, Tübingen 72070, Germany [3] Max Planck Institute for Science and History, Khalaische Straße 10, 07745 Jena, Germany.

Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean.
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http://dx.doi.org/10.1038/nature13591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550673PMC
October 2014

Microbial community analysis using MEGAN.

Methods Enzymol 2013 ;531:465-85

Center for Bioinformatics, University of Tübingen, Tübingen, Germany. Electronic address:

Metagenomics, the study of microbes in the environment using DNA sequencing, depends upon dedicated software tools for processing and analyzing very large sequencing datasets. One such tool is MEGAN (MEtaGenome ANalyzer), which can be used to interactively analyze and compare metagenomic and metatranscriptomic data, both taxonomically and functionally. To perform a taxonomic analysis, the program places the reads onto the NCBI taxonomy, while functional analysis is performed by mapping reads to the SEED, COG, and KEGG classifications. Samples can be compared taxonomically and functionally, using a wide range of different charting and visualization techniques. PCoA analysis and clustering methods allow high-level comparison of large numbers of samples. Different attributes of the samples can be captured and used within analysis. The program supports various input formats for loading data and can export analysis results in different text-based and graphical formats. The program is designed to work with very large samples containing many millions of reads. It is written in Java and installers for the three major computer operating systems are available from http://www-ab.informatik.uni-tuebingen.de.
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http://dx.doi.org/10.1016/B978-0-12-407863-5.00021-6DOI Listing
April 2014

Primary hypertension in childhood.

Curr Hypertens Rep 2013 Oct;15(5):444-52

Pediatric Nephrology, University Children's Hospital, Inselspital and University of Bern, 3010, Bern, Switzerland.

There is growing concern about elevated blood pressure in children and adolescents, because of its association with the obesity epidemic. Moreover, cardiovascular function and blood pressure level are determined in childhood and track into adulthood. Primary hypertension in childhood is defined by persistent blood pressure values ≥ the 95th percentile and without a secondary cause. Preventable risk factors for elevated blood pressure in childhood are overweight, dietary habits, salt intake, sedentary lifestyle, poor sleep quality and passive smoking, whereas non-preventable risk factors include race, gender, genetic background, low birth weight, prematurity, and socioeconomic inequalities. Several different pathways are implicated in the development of primary hypertension, including obesity, insulin resistance, activation of the sympathetic nervous system, alterations in sodium homeostasis, renin-angiotensin system and altered vascular function. Prevention of adult cardiovascular disease should begin in childhood by regularly screening for high blood pressure, counseling for healthy lifestyle and avoiding preventable risk factors.
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http://dx.doi.org/10.1007/s11906-013-0378-8DOI Listing
October 2013

Integrative analysis of environmental sequences using MEGAN4.

Genome Res 2011 Sep 20;21(9):1552-60. Epub 2011 Jun 20.

Center for Bioinformatics, Tübingen University, Tübingen, Germany.

A major challenge in the analysis of environmental sequences is data integration. The question is how to analyze different types of data in a unified approach, addressing both the taxonomic and functional aspects. To facilitate such analyses, we have substantially extended MEGAN, a widely used taxonomic analysis program. The new program, MEGAN4, provides an integrated approach to the taxonomic and functional analysis of metagenomic, metatranscriptomic, metaproteomic, and rRNA data. While taxonomic analysis is performed based on the NCBI taxonomy, functional analysis is performed using the SEED classification of subsystems and functional roles or the KEGG classification of pathways and enzymes. A number of examples illustrate how such analyses can be performed, and show that one can also import and compare classification results obtained using others' tools. MEGAN4 is freely available for academic purposes, and installers for all three major operating systems can be downloaded from www-ab.informatik.uni-tuebingen.de/software/megan.
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http://dx.doi.org/10.1101/gr.120618.111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166839PMC
September 2011