Highlights d mTOR and AMPK modulation by rapamycin, metformin, and a-KG induces anagen hair growth d Autophagy induction is necessary and sufficient for anagen entry and hair growth d Autophagy is increased during anagen phase of the natural hair follicle cycle d Aged mice fed the autophagy-inducing metabolite a-KB are protected from hair loss
Substantial progress has been made in elucidating the molecular processes that impart a temporal control to physiology and behavior in most eukaryotes. In Drosophila, dorsal and ventral neuronal networks act in concert to convey rhythmicity. Recently, the hierarchical organization among the different circadian clusters has been addressed, but how molecular oscillations translate into rhythmic behavior remains unclear. The small ventral lateral neurons can synchronize certain dorsal oscillators likely through the release of pigment dispersing factor (PDF), a neuropeptide central to the control of rhythmic rest-activity cycles. In the present study, we have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the potassium channel slowpoke (slo) to examine the relevance of specific neuronal populations involved in the circadian control of behavior. We show that altered neuronal function associated with the null mutation specifically impaired PDF accumulation in the dorsal protocerebrum and, in turn, desynchronized molecular oscillations in the dorsal clusters. However, molecular oscillations in the small ventral lateral neurons are properly running in the null mutant, indicating that slo is acting downstream of these core pacemaker cells, most likely in the output pathway. Surprisingly, disrupted PDF signaling by slo dysfunction directly affects the structure of the underlying circuit. Our observations demonstrate that subtle structural changes within the circadian network are responsible for behavioral arrhythmicity.circadian circuitry ͉ Drosophila ͉ pigment dispersing factor ͉ potassium channels ͉ slowpoke R hythmicity in rest-activity cycles in Drosophila is under control of the circadian clock, which is based on selfsustaining, cell-autonomous transcriptional negative feedback loops. These feedback loops ultimately give rise to rhythms in the abundance, phosphorylation state, and nuclear localization of key intracellular proteins, such as period (PER) and timeless (TIM) (1). To date, several neuronal clusters have been shown to include a molecular oscillator. The one best understood encompasses the small ventral lateral neurons (LNvs), comprised of five cells, of which four rhythmically release the neuropeptide pigment dispersing factor (PDF) at their dorsal terminals. Other oscillators within the fly brain include the dorsal lateral neurons (LNds) together with the dorsal neurons (DN1-3) (2). Ablation of all LNvs by overexpression of proapoptotic genes, as well as null mutations on the pdf gene or its receptor, cause behavioral arrhythmicity a few days upon transfer to constant conditions (3-6) likely through the gradual loss of synchronization among the components of the small LNv cluster (7).The question of how the intracellular molecular oscillations taking place within specific neuronal clusters ultimately drive rhythmic locomotor activity has only recently been approached in Drosophila (7-11). Molecular oscillations must be somehow transduced into neuronal function to...
Plant seeds store triacylglycerols in discrete organelles called oil bodies. An oil body stores a matrix of triacylglycerols surrounded by phospholipids and alkaline proteins termed oleosins. Oil bodies in rice seeds are present in embryos and aleurone layers. They do not coalesce in crowded environments, as observed on electron microscopy. The detected isoelectric point of purified rice oil bodies is pH 6.2. This implies that rice oil bodies possess a negatively charged surface at neutral pH. The suspension of rice oil bodies in pH 6.5 buffer induces aggregation. Presumably, the negatively charged surface causes electrostatic repulsion that maintains rice oil bodies as discrete organelles. Rice oil bodies lose their integrity on trypsin treatment. Undoubtedly, oleosins play an important role in the stability of oil bodies. There are two oleosin isoforms in rice oil bodies. Antibodies raised against these two homologous isoforms do not cross-recognize each other. Both isoforms are restricted to oil bodies, as detected on immuno-assaying. Partial amino acid sequences of these two isoforms were obtained, and compared with the deduced sequences of two maize and two rice oleosin genes. The comparison confirmed that the two major proteins in rice oil bodies are the two oleosin isoforms.
The Distal-less gene is known for its role in proximodistal patterning of Drosophila limbs. However, Distal-less has a second critical function during Drosophila limb development, that of distinguishing the antenna from the leg. The antenna-specifying activity of Distal-less is genetically separable from the proximodistal patterning function in that certain Distal-less allelic combinations exhibit antenna-to-leg transformations without proximodistal truncations. Here, we show that Distal-less acts in parallel with homothorax, a previously identified antennal selector gene, to induce antennal differentiation. While mutations in either Distal-less or homothorax cause antenna-to-leg transformations, neither gene is required for the others expression, and both genes are required for antennal expression of spalt. Coexpression of Distal-less and homothorax activates ectopic spalt expression and can induce the formation of ectopic antennae at novel locations in the body, including the head, the legs, the wings and the genital disc derivatives. Ectopic expression of homothorax alone is insufficient to induce antennal differentiation from most limb fields, including that of the wing. Distal-less therefore is required for more than induction of a proximodistal axis upon which homothorax superimposes antennal identity. Based on their genetic and biochemical properties, we propose that Homothorax and Extradenticle may serve as antenna-specific cofactors for Distal-less.
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