Recent CIG publications Archive

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Genome Res.: auth.: group Dessimoz

 2019 Jun 24. doi: 10.1101/gr.243212.118. [Epub ahead of print]

OMA standalone: orthology inference among public and custom genomes and transcriptomes.

Abstract

Genomes and transcriptomes are now typically sequenced by individual laboratories but analyzing them often remains challenging. One essential step in many analyses lies in identifying orthologs-corresponding genes across multiple species-but this is far from trivial. The Orthologous MAtrix (OMA) database is a leading resource for identifying orthologs among publicly available, complete genomes. Here, we describe the OMA pipeline available as a standalone program for Linux and Mac. When run on a cluster, it has native support for the LSF, SGE, PBS Pro, and Slurm job schedulers and can scale up to thousands of parallel processes. Another key feature of OMA standalone is that users can combine their own data with existing public data by exporting genomes and precomputed alignments from the OMA database, which currently contains over 2100 complete genomes. We compare OMA standalone to other methods in the context of phylogenetic tree inference, by inferring a phylogeny of Lophotrochozoa, a challenging clade within the protostomes. We also discuss other potential applications of OMA standalone, including identifying gene families having undergone duplications/losses in specific clades, and identifying potential drug targets in nonmodel organisms. OMA standalone is available under the permissive open source Mozilla Public License Version 2.0.

PMID: 31235654
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FASEB J.: auth.: W. Wahli

 2019 Jun 25:fj201802681RR. doi: 10.1096/fj.201802681RR. [Epub ahead of print]

The PPAR-microbiota-metabolic organ trilogy to fine-tune physiology.

Oh HYP#1,2Visvalingam V#2Wahli W2,3,4.

Abstract

The human gut is colonized by commensal microorganisms, predominately bacteria that have coevolved in symbiosis with their host. The gut microbiota has been extensively studied in recent years, and many important findings on how it can regulate host metabolism have been unraveled. In healthy individuals, feeding timing and type of food can influence not only the composition but also the circadian oscillation of the gut microbiota. Host feeding habits thus influence the type of microbial-derived metabolites produced and their concentrations throughout the day. These microbial-derived metabolites influence many aspects of host physiology, including energy metabolism and circadian rhythm. Peroxisome proliferator-activated receptors (PPARs) are a group of ligand-activated transcription factors that regulate various metabolic processes such as fatty acid metabolism. Similar to the gut microbiota, PPAR expression in various organs oscillates diurnally, and studies have shown that the gut microbiota can influence PPAR activities in various metabolic organs. For example, short-chain fatty acids, the most abundant type of metabolites produced by anaerobic fermentation of dietary fibers by the gut microbiota, are PPAR agonists. In this review, we highlight how the gut microbiota can regulate PPARs in key metabolic organs, namely, in the intestines, liver, and muscle. Knowing that the gut microbiota impacts metabolism and is altered in individuals with metabolic diseases might allow treatment of these patients using noninvasive procedures such as gut microbiota manipulation.-Oh, H. Y. P., Visvalingam, V., Wahli, W. The PPAR-microbiota-metabolic organ trilogy to fine-tune physiology.

KEYWORDS:

circadian rhythm; intestines; liver; muscle

PMID: 31237779

 

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Diabetologia.: co-auth.: B.Thorens

 2019 Jun 13. doi: 10.1007/s00125-019-4911-4. [Epub ahead of print]

Fostering improved human islet research: a European perspective.

KEYWORDS:

Beta cells; Diabetes research; Human islets

PMID: 31197398

 

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Dev Neurobiol.: auth.: group Herr

 2019 Jun 17. doi: 10.1002/dneu.22704. [Epub ahead of print]

Cortical and commissural defects upon HCF-1 loss in Nkx2.1-derived embryonic neurons and glia.

Abstract

Formation of the cerebral cortex and commissures involves a complex developmental process defined by multiple molecular mechanisms governing proliferation of neuronal and glial precursors, neuronal and glial migration, and patterning events. Failure in any of these processes can lead to malformations. Here, we study the role of HCF-1 in these processes. HCF-1 is a conserved metazoan transcriptional co-regulator long implicated in cell proliferation and more recently in human metabolic disorders and mental retardation. Loss of HCF-1 in a subset of ventral telencephalic Nkx2.1-positive progenitors leads to reduced numbers of GABAergic interneurons and glia, owing not to decreased proliferation but rather to increased apoptosis before cell migration. The loss of these cells leads to development of severe commissural and cortical defects in early postnatal mouse brains. These defects include mild and severe structural defects of the corpus callosum and anterior commissure, respectively, and increased folding of the cortex resembling polymicrogyria. Hence, in addition to its well-established role in cell proliferation, HCF-1 is important for organ development, here the brain. This article is protected by copyright. All rights reserved.

KEYWORDS:

GABAergic neurons; Nkx2.1; anterior commissure; corpus callosum; cortex; glia; polymicrogyria

PMID: 31207118

 

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Cardiovasc Diabetol.: co-auth.: W. Wahli

 2019 Jun 4;18(1):71. doi: 10.1186/s12933-019-0864-7.

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.

Abstract

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

KEYWORDS:

Atherogenic dyslipidemia; Diabetes; Inflammation; PROMINENT; Pemafibrate (K-877); Remnant cholesterol; Residual cardiovascular risk; SPPARMalpha; Selective peroxisome proliferator-activated receptor alpha modulator; Triglycerides; Visceral obesity

PMID: 31164165
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Diabetes Metab.: co-auth.: W. Wahli

 2019 Jun 1. pii: S1262-3636(19)30088-6. doi: 10.1016/j.diabet.2019.05.005. [Epub ahead of print]

Regulation of hepatokine gene expression in response to fasting and feeding: Influence of PPAR-α and insulin-dependent signalling in hepatocytes.

Abstract

AIM:

– In hepatocytes, the peroxisome proliferator-activated receptor (PPAR)-α and insulin receptor (IR) are critical for transcriptional responses to fasting and feeding, respectively. The present report analyzes the effects of nutritional status (fasting vs feeding) on the expression of a large panel of hepatokines in hepatocyte-specific PPAR-α (Pparα hep-/-) and IR (IRhep-/-) null mice.

METHODS:

– Pparαhep-/- and IRhep-/- mice, and their wild-type littermates, were subjected to fasting or feeding metabolic challenges, then analyzed for hepatokine gene expression. Experiments were conducted in mice of both genders.

RESULTS:

– Our data confirmed that PPAR-α is essential for regulating fasting-induced Fgf21 and Angptl4 expression. In mice lacking PPAR-α, fasting led to increased Igfbp1 and Gdf15 gene expression. In the absence of hepatic IR, feeding induced overexpression of Igfbp1, follistatin (Fst) and adropin (Enho), and reduced activin E (Inhbe) expression. Gender had only a modest influence on hepatokine gene expression in the liver.

CONCLUSION:

– The present results highlight the potential roles of hepatokines as a class of hormones that substantially influence nutritional regulation in both female and male mice.

KEYWORDS:

Hepatokines; Insulin receptor; Nutritional regulation; PPAR-α

PMID: 31163275