LRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells.

Adult neural stem cells (NSCs) must tightly regulate quiescence and proliferation. Single-cell analysis has suggested a continuum of cell states as NSCs exit quiescence. Here we capture and characterize in vitro primed quiescent NSCs and identify LRIG1 as an important regulator.

Targeting of early endosomes by autophagy facilitates EGFR recycling and signalling.

Despite recently uncovered connections between autophagy and the endocytic pathway, the role of autophagy in regulating endosomal function remains incompletely understood. Here, we find that the ablation of autophagy-essential players disrupts EGF-induced endocytic trafficking of EGFR. Cells lacking ATG7 or ATG16L1 exhibit increased levels of phosphatidylinositol-3-phosphate (PI(3)P), a key determinant of early endosome maturation.

Interplay of autophagy, receptor tyrosine kinase signalling and endocytic trafficking.

Vesicular trafficking events play key roles in the compartmentalization and proper sorting of cellular components. These events have crucial roles in sensing external signals, regulating protein activities and stimulating cell growth or death decisions. Although mutations in vesicle trafficking players are not direct drivers of cellular transformation, their activities are important in facilitating oncogenic pathways.

Suppression of autophagy impedes glioblastoma development and induces senescence.

The function of macroautophagy/autophagy during tumor initiation or in established tumors can be highly distinct and context-dependent. To investigate the role of autophagy in gliomagenesis, we utilized a KRAS-driven glioblastoma mouse model in which autophagy is specifically disrupted via RNAi against Atg7, Atg13 or Ulk1. Inhibition of autophagy strongly reduced glioblastoma development, demonstrating its critical role in promoting tumor formation.

Solubility parameter-based screening methods for early-stage formulation development of itraconazole amorphous solid dispersions.

Objectives: This article uses conventional and newly extended solubility parameter (δ) methods to identify polymeric materials capable of forming amorphous dispersions with itraconazole (itz).

Methods: Combinations of itz and Soluplus, Eudragit E PO (EPO), Kollidon 17PF (17PF) or Kollidon VA64 (VA64) were prepared as amorphous solid dispersions using quench cooling and hot melt extrusion. Storage stability was evaluated under a range of conditions using differential scanning calorimetry and powder X-ray diffraction.

Post-genomic approaches to understanding the mechanisms of environmentally induced phenotypic plasticity.

Post-genomic techniques offer new and detailed insights into the mechanisms underpinning all biological processes, including phenotypic plasticity and environmentally relevant phenotypes. Although they require access to genomic resources it is now possible to create these for species of comparative or environmental interest even within a modest research project. Here we describe an open transcript screen for genes responding to environmental cold that might account for the acquired cold-specific phenotype in all its complex manifestations.

Hypoxia-inducible myoglobin expression in nonmuscle tissues.

Myoglobin (Myg) is an oxygen-binding hemoprotein that is widely thought to be expressed exclusively in oxidative skeletal and cardiac myocytes, where it plays a key role in coping with chronic hypoxia. We now show in a hypoxia-tolerant fish model, that Myg is also expressed in a range of other tissues, including liver, gill, and brain. Moreover, expression of Myg transcript was substantially enhanced during chronic hypoxia, the fold-change induction being far greater in liver than muscle.

Coping with cold: An integrative, multitissue analysis of the transcriptome of a poikilothermic vertebrate.

How do organisms respond adaptively to environmental stress? Although some gene-specific responses have been explored, others remain to be identified, and there is a very poor understanding of the system-wide integration of response, particularly in complex, multitissue animals. Here, we adopt a transcript screening approach to explore the mechanisms underpinning a major, whole-body phenotypic transition in a vertebrate animal that naturally experiences extreme environmental stress. Carp were exposed to increasing levels of cold, and responses across seven tissues were assessed by using a microarray composed of 13,440 cDNA probes.

Isolation increases milt production in goldfish.

Milt volume in goldfish is increased by female steroid and prostaglandin pheromones, by exposure to males with elevated gonadotropin levels, and by isolation from conspecifies. This study examined various aspects of the isolation effect on milt volume and serum gonadotropin II (GTH II). The latency of isolation-induced milt increase in this study (12-24 hr) was longer than the latencies to pheromone-induced milt increase in previous work (0.