Transition from proliferation to quiescence brings about extensive changes in cellular behavior and structure. However, the genes that are crucial for establishing and/or maintaining quiescence are largely unknown. The fission yeast Schizosaccharomyces pombe is an excellent model in which to study this problem, because it becomes quiescent under nitrogen starvation. Here, we characterize 610 temperature-sensitive mutants, and identify 33 genes that are required for entry into and maintenance of quiescence. These genes cover a broad range of cellular functions in the cytoplasm, membrane and nucleus. They encode proteins for stress-responsive and cell-cycle kinase signaling pathways, for actin-bound and osmo-controlling endosome formation, for RNA transcription, splicing and ribosome biogenesis, for chromatin silencing, for biosynthesis of lipids and ATP, for cell-wall and membrane morphogenesis, and for protein trafficking and vesicle fusion. We specifically highlight Fcp1, a CTD phosphatase of RNA polymerase II, which differentially affects the transcription of genes that are involved in quiescence and proliferation. We propose that the transcriptional role of Fcp1 is central in differentiating quiescence from proliferation.

Keratinocytes produce not only interleukin 1 (IL-1) but also IL-1 receptor antagonist (IL-1ra), a competitive inhibitor of IL-1. Because little is known about the presence of IL-1ra in the stratum corneum, we examined the content of IL-1ra in the stratum corneum, especially the balance between IL-1 and IL-1ra. IL-1 alpha and IL-1ra, but not IL-1 beta, were detected in the tape-stripped stratum corneum of healthy volunteers by enzyme-linked immunosorbent assays. IL-1 alpha and IL-1ra were bioactive as determined by thymocyte co-stimulation assay, and their molecular masses were 17 and 20 kDa, respectively, suggesting that the stratum corneum contains active forms of IL-1 alpha and IL-1ra produced by keratinocytes. The stratum corneum of an unexposed area, the inner side of the upper arm. contained more IL-1 alpha than a sun-exposed area, the face. In contrast, the stratum corneum of the sun-exposed area contained a markedly higher amount of IL-1ra than that of the unexposed area. The ratio of IL-1ra to IL-1 alpha was 8 in the unexposed area, and over 100 in the sun-exposed area. Therefore, IL-1 alpha activity was dominant in the unexposed area, and in contrast, IL-1ra activity was dominant in the sun-exposed area. An elevated level of IL-1ra was detected in the stratum corneum of the sun-exposed area independently of age. In the unexposed area, however, IL-1a increased, but IL-1ra decreased, with age, resulting in a significant decline of the ratio of IL-1ra to IL-1a with increasing age. Irradiation of 2 MED of ultraviolet B to the back skin, an unexposed area, resulted in striking elevation of IL-1ra in the stratum corneum in desquamating scales. These data suggest that IL-1ra in the epidermis may be inducible by chronic UV irradiation, although IL-1ra production in the epidermis may decrease with aging in the absence of any stimulus. IL-1ra in the epidermis may play a role in the regulation of IL-1-induced inflammatory responses, and an appropriate balance between IL-1 and IL-1ra may help to maintain homeostasis of the skin.

Many debilitating neuropsychiatric and neurodegenerative disorders are characterized by dopamine neurotransmitter dysregulation. Monitoring subsecond dopamine release accurately and for extended, clinically relevant timescales is a critical unmet need. Especially valuable has been the development of electrochemical fast-scan cyclic voltammetry implementing microsized carbon fiber probe implants to record fast millisecond changes in dopamine concentrations. Nevertheless, these well-established methods have only been applied in primates with acutely (few hours) implanted sensors. Neurochemical monitoring for long timescales is necessary to improve diagnostic and therapeutic procedures for a wide range of neurological disorders. Strategies for the chronic use of such sensors have recently been established successfully in rodents, but new infrastructures are needed to enable these strategies in primates. Here we report an integrated neurochemical recording platform for monitoring dopamine release from sensors chronically implanted in deep brain structures of nonhuman primates for over 100 days, together with results for behavior-related and stimulation-induced dopamine release. From these chronically implanted probes, we measured dopamine release from multiple sites in the striatum as induced by behavioral performance and reward-related stimuli, by direct stimulation, and by drug administration. We further developed algorithms to automate detection of dopamine. These algorithms could be used to track the effects of drugs on endogenous dopamine neurotransmission, as well as to evaluate the long-term performance of the chronically implanted sensors. Our chronic measurements demonstrate the feasibility of measuring subsecond dopamine release from deep brain circuits of awake, behaving primates in a longitudinally reproducible manner.

IFN-gamma is the most abundant cytokine in infectious and noninfectious uveitis, with a remarkable difference between the two groups. The data suggest that cytokines in AqH of infectious uveitis are locally produced, whereas in noninfectious uveitis, IFN-gamma is produced both in the eye and the peripheral blood.