In brief, this publication describes the detailed gene-level execution of zygote development in the first two hours after the fusion of two sexual gametes via RNA-seq transcriptome analysis. Two major conclusions are: 1) the majority of differentially regulated genes during zygote development is under the control of the GSM1/GSP1 heterodimeric homeobox transcription factors; and 2) the transition from gamete to zygote is executed by transcriptional activation of zygote-specific genes and post-transcriptional inhibition of vegetative/gamete-specific transcripts.
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For the first time, we have provided in vivo evidence of demyelination in individuals with non-traumatic spinal cord injury. This was done using an MRI technique called myelin water imaging that is specifically sensitive to changes in myelination (validated in more conventional diseases associated with demyelination, like multiple sclerosis).This is important because it would suggest demyelination is a pathophysiological process of non-traumatic spinal cord injury and that targeting myelin...
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Carbonic anhydrase IX (CAIX) is a hypoxia inducible factor 1-induced, cell surface pH regulating enzyme with an established role in tumor progression and clinical outcome. However, the molecular basis of CAIX-mediated tumor progression remains unclear. Here, we have utilized proximity dependent biotinylation (BioID) to map the CAIX ‘interactome’ in breast cancer cells in order to identify physiologically relevant CAIX-associating proteins…
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REVIEW: Genes and Molecular Pathways Underpinning Ciliopathies

Motile and non-motile (primary) cilia are nearly ubiquitous cellular organelles. The dysfunction of cilia causes diseases known as ciliopathies. The number of reported ciliopathies (currently 35) is increasing, as is the number of established (187) and candidate (241) ciliopathy-associated genes. The characterization of ciliopathy-associated proteins and phenotypes has improved our knowledge of ciliary functions. In particular, investigating ciliopathies has helped…
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Our well-powered study had two major findings, both of which have profound implications across multiple fields.  First, we found that mild life-long reduction in circulating insulin improves glucose homeostasis and insulin sensitivity in old mice. This demonstrates that at least some age-dependent insulin resistance is caused by the hypersecretion of insulin itself. This simple observation is the first clear evidence of causality to one of the most important chicken-and-egg debates in the metabolism field...
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Mutations in genes encoding epigenetic regulators as well as mutations in the histones they modify are increasingly recognized as drivers of transformation. Mutations in DNA methylation regulators have been identified as frequent early events in the generation of acute myeloid leukemia (AML) clones and are also found at high frequency in expanded, but apparently otherwise normal clones of blood cells in older people.
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KCNQ5 is a highly conserved gene encoding an important channel for neuronal function; it is widely expressed in the brain and generates M-type current. Exome sequencing identified de novo heterozygous missense mutations in four probands with intellectual disability, abnormal neurological findings, and treatment-resistant epilepsy (in two of four). Comprehensive analysis of this potassium channel for the four variants expressed in…
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Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis-derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype-specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to…
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Read the Publication  This week we profile a recent publication in Nature Communications from Dr. Craig Brown (left) and Dr. Kelly Tennant (right). Can you provide a brief overview of your lab’s current research focus? The primary goal of our research is to understand the mechanisms of brain repair. In particular, we are interested in how stroke and co-morbidities like diabetes…
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Myelin Regulatory Factor Drives Remyelination in Multiple Sclerosis

Remyelination is limited in the majority of multiple sclerosis (MS) lesions despite the presence of oligodendrocyte precursor cells (OPCs) in most lesions. This observation has led to the view that a failure of OPCs to fully differentiate underlies remyelination failure. OPC differentiation requires intricate transcriptional regulation, which may be disrupted in chronic MS lesions. The expression of few transcription factors…
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