De Novo Mutations in YWHAG Cause Early-Onset Epilepsy

Read the Publication  This week we profile a recent publication in the American Journal of Human Genetics from the laboratory of Dr. Matthew Farrer (pictured) at the Centre for Applied Neurogenetics Can you provide a brief overview of your lab’s current research focus? The focus of the lab is ‘applied neurogenetics’. One aspect is making recent advances in human genome…
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Bacterial sporulation allows starving cells to differentiate into metabolically dormant spores that can survive extreme conditions. Following asymmetric division, the mother cell engulfs the forespore, surrounding it with two bilayer membranes. During the engulfment process, an essential channel, the so-called feeding tube apparatus, is thought to cross both membranes to create a direct conduit between the mother cell and the…
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β-cell dysfunction and apoptosis associated with islet inflammation play a key role in the pathogenesis of type 2 diabetes (T2D). Growing evidence suggests that islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to islet inflammation and β-cell death in T2D. We recently showed the role of interleukin-1β (IL-1β)/Fas/caspase-8 apoptotic pathway in amyloid-induced β-cell death. In this…
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Infants born preterm are highly susceptible to various environmental stressors during their first few weeks of life. Their brain, in particular their cerebellum, are in active growth and any changes that might interfere with this growth process may lead to developmental problems. Despite our capacity to detect and diagnose…
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ReMixT: Clone-Specific Genomic Structure Estimation in Cancer

Somatic evolution of malignant cells produces tumors composed of multiple clonal populations, distinguished in part by rearrangements and copy number changes affecting chromosomal segments. Whole genome sequencing mixes the signals of sampled populations, diluting the signals of clone-specific aberrations, and complicating estimation of clone-specific genotypes. We introduce ReMixT, a method to unmix tumor and contaminating normal signals and jointly predict…
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Circulating Tumor DNA Reveals Clinically-Actionable Somatic Genome of Metastatic Bladder Cancer

Exciting new treatment options have recently emerged for metastatic bladder cancer. However, because each patient’s cancer has distinct ‘molecular’ features, patient responses to these new therapies are highly variable. Therefore, efforts are underway to develop tools for determining the ideal therapy for each individual based…
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Glycosyl Cations versus Allylic Cations in Spontaneous and Enzymatic Hydrolysis

This work has allowed the first direct comparison of fundamental rates of two key classes of biologically relevant reactions: glycosyl transfer and prenyl transfer. On the way we have uncovered a new class of non-sugar substrate for the enzymes we most study, the glycosidases (aka glycoside hydrolases). This opens up potential to engineer these enzymes…
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Can We Predict Protein from mRNA Levels?

Recent advances of genomic, proteomic, and metabolomics technologies have stimulated a large body of biomedical studies focused on the identification of molecular biomarkers that can reduce the challenges and costs associated with the prediction, diagnosis, and management of various diseases. In general, these technologies have been used separately and the integration of the information distilled from these platforms to jointly address…
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New Class of Glycoside Hydrolase Mechanism-Based Covalent Inhibitors: Glycosylation Transition State Conformations

The design of covalent inhibitors in glycoscience research is important for the development of chemical biology probes. Here we report the synthesis of a new carbocyclic mechanism-based covalent inhibitor of an α-glucosidase. The enzyme efficiently catalyzes its alkylation via either an allylic cation or a cationic transition state. We show this allylic covalent inhibitor has different catalytic proficiencies for pseudoglycosylation…
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Oral sucrose is administered routinely to reduce pain of minor procedures in premature infants and is recommended as standard care in international guidelines. No human or animal studies on effects of early repeated sucrose exposure on long-term brain development have been done in the context of pain. We evaluated the effects of repeated neonatal sucrose treatment before an intervention on…
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