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Alabi, N.

Publications and source records attributed to Alabi, N..

3 recordsLinked to original sources

Sex dimorphism in the aged metabolic phenotype of smoothelin-like 1 (SMTNL1) deficient mice

Smoothelin-like 1 (SMTNL1) is expressed in smooth and skeletal muscle tissues as well as a variety of steroid hormone-sensitive tissues. SMTNL1 can play a sex-dependent regulatory role in skeletal muscle metabolism in mice. Previous studies have documented appreciable changes in muscle morphology and metabolic function of young male mice with genetic deletion of Smtnl1. SMTNL1 can also impact the energy metabolism and insulin sensitivity of female mice during pregnancy. Therefore, we investigated the metabolic outcome of global SMTNL1 knockout (KO) in male and female mice with advancing age using a comprehensive lab animal monitoring system (CLAMS). With ageing, body weight gain was markedly higher with a concomitant increase in whole body adiposity as well as specific white adipose depots in the absence of SMTNL1. Moreover, this genotypic difference in whole body adiposity was greater in the female cohort. The deletion of SMTNL1 was also associated with delayed satiety in mice fed a high fat diet, which was more pronounced in the female mice. A significant genotypic difference was also revealed for the metabolic energy balance in 12 month old animals of both sexes. The KO animals were metabolically less efficient and displayed a preference for carbohydrate catabolism. However, reduced glucose tolerance was observed only in the female group with the deletion of SMTNL1. Taken together, the current findings establish a novel role for SMTNL1 in modulating adiposity and energy metabolism with ageing in a sex dimorphic way.

biochemistry↗

A Clinically Useful and Biologically Informative Genomic Classifier for Papillary Thyroid Cancer

Clinical management of papillary thyroid cancer depends on estimations of prognosis. Standard care, which relies on prognostication based on clinicopathologic features, is inaccurate. We applied a machine learning algorithm (HighLifeR) to 502 cases annotated by The Cancer Genome Atlas Project to derive an accurate molecular prognostic classifier. Unsupervised analysis of the 82 genes that were most closely associated with recurrence after surgery enabled identification of three unique molecular subtypes. One subtype had a high recurrence rate, an immunosuppressed microenvironment, and enrichment of the EZH2-HOTAIR pathway. Two other unique molecular subtypes with a lower rate of recurrence were identified, including one subtype with a paucity of BRAFV600E mutations and a high rate of RAS mutations. The genomic risk classifier, in addition to tumor size and lymph node status, enabled effective prognostication that outperformed the American Thyroid Association clinical risk stratification. The genomic classifier we derived can potentially be applied preoperatively to direct clinical decision-making. Distinct biological features of molecular subtypes also have implications regarding sensitivity to radioactive iodine, EZH2 inhibitors, and immune checkpoint inhibitors.

cancer biology↗

A draft genome of Alliaria petiolata (garlic mustard) as a model system for invasion genetics

The emerging field of invasion genetics examines the genetic causes and consequences of biological invasions, but few study systems are available that integrate deep ecological knowledge with genomic tools. Here we report on the de novo assembly and annotation of a genome for the biennial herb Alliaria petiolata (M. Bieb.) Cavara & Grande (Brassicaceae), which is widespread in Eurasia and invasive across much of temperate North America. Our goal was to sequence and annotate a genome to complement resources available from hundreds of published ecological studies, a global field survey, and hundreds of genetic lines maintained in Germany and Canada. We sequenced a genotype (EFCC-3-20) collected from the native range near Venice, Italy and sequenced paired-end and mate pair libraries at ~70 x coverage. A de novo assembly resulted in a highly continuous draft genome (N50 = 121 Mb; L50 = 2) with 99.7 % of the 1.1 Gb genome mapping to scaffolds of at least 50 Kb in length. A total of 64,770 predicted genes in the annotated genome include 99 % of plant BUSCO genes and 98 % of transcriptome reads. Consistent with previous reports of (auto)hexaploidy in western Europe, we found that almost one third of BUSCO genes (390/1440) mapped to two or more scaffolds despite < 2 % genome-wide average heterozygosity. The continuity and gene space quality of our draft assembly will enable molecular and functional genomic studies of A. petiolata to address questions relevant to invasion genetics and conservation strategies.

genomics↗