CRISPR-Cas enzymes enable RNA-guided bacterial immunity and are widely used for biotechnological applications including genome editing. In particular, the Class 2 CRISPR-associated enzymes (Cas9, Cas12 and Cas13 families), have been deployed for numerous research, clinical and agricultural applications. However, the immense genetic and biochemical diversity of these proteins in the public domain poses a barrier for researchers seeking to leverage their activities.
View Article and Find Full Text PDFThe nervous system plays a critical role in maintaining whole-organism homeostasis; neurons experiencing mitochondrial stress can coordinate the induction of protective cellular pathways, such as the mitochondrial unfolded protein response (UPR), between tissues. However, these studies largely ignored nonneuronal cells of the nervous system. Here, we found that UPR activation in four astrocyte-like glial cells in the nematode, , can promote protein homeostasis by alleviating protein aggregation in neurons.
View Article and Find Full Text PDFThe nervous system plays a critical role in maintaining whole-organism homeostasis; neurons experiencing mitochondrial stress can coordinate the induction of protective cellular pathways, such as the mitochondrial unfolded protein response (UPR), between tissues. However, these studies largely ignored non-neuronal cells of the nervous system. Here, we found that UPR activation in four, astrocyte-like glial cells in the nematode, , can promote protein homeostasis by alleviating protein aggregation in neurons.
View Article and Find Full Text PDFAutophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion.
View Article and Find Full Text PDF5-Hydroxymethylcytosine (5hmC) is a newly discovered DNA base present at detectable levels in most mammalian cell types and tissues. It is generated by Tet-enzyme-mediated oxidation of 5-methylcytosine (5mC). 5hmC is important both because of its potential role in regulating gene expression and because it may be an intermediate in DNA demethylation.
View Article and Find Full Text PDF5-hydroxymethylcytosine (5hmC) is a modified base present at low levels in diverse cell types in mammals. 5hmC is generated by the TET family of Fe(II) and 2-oxoglutarate-dependent enzymes through oxidation of 5-methylcytosine (5mC). 5hmC and TET proteins have been implicated in stem cell biology and cancer, but information on the genome-wide distribution of 5hmC is limited.
View Article and Find Full Text PDFWe report the crystal structure of two variants of Drosophila melanogaster insulin-like peptide 5 (DILP5) at a resolution of 1.85 Å. DILP5 shares the basic fold of the insulin peptide family (T conformation) but with a disordered B-chain C terminus.
View Article and Find Full Text PDFBackground: Phase 1 oncology trial participants often are excluded from hospice. However, it is not known whether they would benefit from hospice services. The objectives of the current study were to define the palliative care needs of these patients and to determine whether their needs are greater than those of other cancer patients.
View Article and Find Full Text PDFBackground: The requirement that patients give up curative treatment makes hospice enrollment unappealing for some patients and may particularly limit use among African-American patients. The current study was conducted to determine whether African-American patients with cancer are more likely than white patients to have preferences for cancer treatment that exclude them from hospice and whether they are less likely to want specific hospice services.
Methods: Two hundred eighty-three patients who were receiving treatment for cancer at 6 oncology clinics within the University of Pennsylvania Cancer Network completed conjoint interviews measuring their perceived need for 5 hospice services and their preferences for continuing cancer treatment.