Publications by authors named "Stephanie Kehr"

Adipose tissue inflammation and insulin resistance are hallmarks in the development of metabolic diseases resulting from overweight and obesity, such as type 2 diabetes and non-alcoholic fatty liver disease. In obesity, adipocytes predominantly secrete proinflammatory adipokines that further promote adipose tissue dysfunction with negative effects on local and systemic insulin sensitivity. Expression of the serpin vaspin (SERPINA12) is also increased in obesity and type 2 diabetes, but exhibits compensatory roles in inflammation and insulin resistance.

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  • Phospholipid scramblase 4 (PLSCR4) is important for redistributing phospholipids in cell membranes and regulating cell signaling, but its specific function in adipose tissue remains unclear amid the roles of PLSCR1 and PLSCR3.* -
  • PLSCR4 is downregulated in adipose-progenitor cells lacking the tumor suppressor PTEN, which is linked to abnormal fat growth and lipoma development in patients.* -
  • Research shows that decreased PLSCR4 leads to increased lipid accumulation and activation of the PI3K/AKT signaling pathway, suggesting that PLSCR4 might help manage fat cell growth and be relevant in conditions associated with PTEN loss
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  • Kidney stone disease (KSD) is common and can lead to serious health issues, with causes linked to both genetics and environment.
  • A study examined a group of patients who underwent kidney stone procedures and used targeted next generation sequencing (tNGS) to identify genetic factors, finding hereditary issues in 6.8% of cases.
  • The research highlighted that early-onset and recurrent KSD is often tied to genetic factors, while metabolic conditions are more common in those with late-onset stones, thus showing the importance of genetic analysis in understanding KSD risks and severity.
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Small integral membrane protein 10 like 1 (SMIM10L1) was identified by RNA sequencing as the most significantly downregulated gene in Phosphatase and Tensin Homologue (PTEN) knockdown adipose progenitor cells (APCs). PTEN is a tumor suppressor that antagonizes the growth promoting Phosphoinositide 3-kinase (PI3K)/AKT/mechanistic Target of Rapamycin (mTOR) cascade. Diseases caused by germline pathogenic variants in PTEN are summarized as PTEN Hamartoma Tumor Syndrome (PHTS).

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Objective: Human white adipose tissue (AT) is a metabolically active organ with distinct depot-specific functions. Despite their locations close to the gastrointestinal tract, mesenteric AT and epiploic AT (epiAT) have only scarcely been investigated. Here, we aim to characterise these ATs in-depth and estimate their contribution to alterations in whole-body metabolism.

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The tumor suppressor phosphatase and tensin homolog (PTEN) negatively regulates the insulin signaling pathway. Germline PTEN pathogenic variants cause PTEN hamartoma tumor syndrome (PHTS), associated with lipoma development in children. Adipose progenitor cells (APCs) lose their capacity to differentiate into adipocytes during continuous culture, whereas APCs from lipomas of patients with PHTS retain their adipogenic potential over a prolonged period.

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The differential associations of adipose depots with metabolic risk during obesity have been proposed to be controlled by environmental and genetic factors. We evaluated the regional differences in transcriptome signatures between abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) in obese black South African women and tested the hypothesis that 12-week exercise training alters gene expression patterns in a depot-specific manner. Twelve young women performed 12-weeks of supervised aerobic and resistance training.

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Subcutaneous (sc) and visceral (vis) adipose tissue (AT) contribute to the variability in pathophysiological consequences of obesity and adverse fat distribution. To gain insights into the molecular mechanisms distinguishing vis and sc fat, we compared the transcriptome during differentiation of immortalized adipocytes from murine epididymal (epi) and inguinal (ing) AT. RNA was extracted on different days of adipogenesis (-2, 0, 2, 4, 6, 8) and analyzed using Clariom™ D mouse assays (Affymetrix) covering >214,900 transcripts in >66,100 genes.

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Background: Lacerta viridis and Lacerta bilineata are sister species of European green lizards (eastern and western clades, respectively) that, until recently, were grouped together as the L. viridis complex. Genetic incompatibilities were observed between lacertid populations through crossing experiments, which led to the delineation of two separate species within the L.

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Recent advances in the stem cell field allow to obtain many human tissues in vitro. However, hepatic differentiation of induced pluripotent stem cells (iPSCs) still remains challenging. Hepatocyte-like cells (HLCs) obtained after differentiation resemble more fetal liver hepatocytes.

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Background: Small nucleolar RNAs (snoRNAs) are one of the most ancient families amongst non-protein-coding RNAs. They are ubiquitous in Archaea and Eukarya but absent in bacteria. Their main function is to target chemical modifications of ribosomal RNAs.

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Small nucleolar RNAs (snoRNAs) are a class of non-coding RNAs that guide the post-transcriptional processing of other non-coding RNAs (mostly ribosomal RNAs), but have also been implicated in processes ranging from microRNA-dependent gene silencing to alternative splicing. In order to construct an up-to-date catalog of human snoRNAs we have combined data from various databases, de novo prediction and extensive literature review. In total, we list more than 750 curated genomic loci that give rise to snoRNA and snoRNA-like genes.

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Here we present the results of a large-scale bioinformatics annotation of non-coding RNA loci in 48 avian genomes. Our approach uses probabilistic models of hand-curated families from the Rfam database to infer conserved RNA families within each avian genome. We supplement these annotations with predictions from the tRNA annotation tool, tRNAscan-SE and microRNAs from miRBase.

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Coilin protein scaffolds Cajal bodies (CBs)-subnuclear compartments enriched in small nuclear RNAs (snRNAs)-and promotes efficient spliceosomal snRNP assembly. The molecular function of coilin, which is intrinsically disordered with no defined motifs, is poorly understood. We use UV crosslinking and immunoprecipitation (iCLIP) to determine whether mammalian coilin binds RNA in vivo and to identify targets.

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Background: Annotating mammalian genomes for noncoding RNAs (ncRNAs) is nontrivial since far from all ncRNAs are known and the computational models are resource demanding. Currently, the human genome holds the best mammalian ncRNA annotation, a result of numerous efforts by several groups. However, a more direct strategy is desired for the increasing number of sequenced mammalian genomes of which some, such as the pig, are relevant as disease models and production animals.

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Motivation: Although small nucleolar RNAs form an important class of non-coding RNAs, no comprehensive annotation efforts have been undertaken, presumably because the task is complicated by both the large number of distinct small nucleolar RNA families and their relatively rapid pace of sequence evolution.

Results: With snoStrip we present an automatic annotation pipeline developed specifically for comparative genomics of small nucleolar RNAs. It makes use of sequence conservation, canonical box motifs as well as secondary structure and predicts putative targets.

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Ribosomal and small nuclear RNAs (snRNAs) comprise numerous modified nucleotides. The modification patterns are retained during evolution, making it even possible to project them from yeast onto human. The stringent conservation of modification sites and the slow evolution of rRNAs and snRNAs contradicts the rapid evolution of small nucleolar RNA (snoRNA) sequences.

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The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications.

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The overwhelming majority of small nucleolar RNAs (snoRNAs) fall into two clearly defined classes characterized by distinctive secondary structures and sequence motifs. A small group of diverse ncRNAs, however, shares the hallmarks of one or both classes of snoRNAs but differs substantially from the norm in some respects. Here, we compile the available information on these exceptional cases, conduct a thorough homology search throughout the available metazoan genomes, provide improved and expanded alignments, and investigate the evolutionary histories of these ncRNA families as well as their mutual relationships.

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Motivation: Small nucleolar RNAs (snoRNAs) are an abundant class of non-coding RNAs with a wide variety of cellular functions including chemical modification of RNA, telomere maintanance, pre-rRNA processing and regulatory activities in alternative splicing. The main role of box C/D snoRNAs is to determine the targets for 2'-O-ribose methylation, which is important for rRNA maturation and splicing regulation of some mRNAs. The targets are still unknown, however, for many 'orphan' snoRNAs.

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Motivation: Small nucleolar RNAs are an abundant class of non-coding RNAs that guide chemical modifications of rRNAs, snRNAs and some mRNAs. In the case of many 'orphan' snoRNAs, the targeted nucleotides remain unknown, however. The box H/ACA subclass determines uridine residues that are to be converted into pseudouridines via specific complementary binding in a well-defined secondary structure configuration that is outside the scope of common RNA (co-)folding algorithms.

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Background: Schistosomes are trematode parasites of the phylum Platyhelminthes. They are considered the most important of the human helminth parasites in terms of morbidity and mortality. Draft genome sequences are now available for Schistosoma mansoni and Schistosoma japonicum.

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