Frequent pathway mutations of splicing machinery in myelodysplasia

Myelodysplastic syndromes and related disorders (myelodysplasia) are a heterogeneous group of myeloid neoplasms showing deregulated blood cell production with evidence of myeloid dysplasia and a predisposition to acute myeloid leukaemia, whose pathogenesis is only incompletely understood. Here we report whole-exome sequencing of 29 myelodysplasia specimens, which unexpectedly revealed novel pathway mutations involving multiple components of the RNA splicing machinery, including U2AF35, ZRSR2, SRSF2 and SF3B1. In a large series analysis, these splicing pathway mutations were frequent (～45 to ～85%) in, and highly specific to, myeloid neoplasms showing features of myelodysplasia. Conspicuously, most of the mutations, which occurred in a mutually exclusive manner, affected genes involved in the 3'-splice site recognition during pre-mRNA processing, inducing abnormal RNA splicing and compromised haematopoiesis. Our results provide the first evidence indicating that genetic alterations of the major splicing components could be involved in human pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia.     

A comparative study of the innervation of the choroid plexus in amphibia

Summary The aminergic and cholinergic innervation of choroid plexuses in three species of amphibia was investigated. Plexuses of the Japanese toad and the bullfrog had poor innervation by adrenergic nerves of sympathetic origin, but in the clawed toad, these plexuses were heavily innervated by adrenergic axons from ganglion cells located in the plexus stroma. Nerve fibers positive for acetylcholinesterase were not found in the plexuses, except for a few fibers with very weak enzyme activity in the clawed toad.Acknowledgment. The authors are very grateful to Prof. T. Wasano (Professor emeritus of Kyushu University) for his encouragement and advice during the course of the present work.     

Antagonism by thyrotropin-releasing hormone (TRH) of pentobarbital-induced hypothermia in rats with brain lesions

Summary Anesthesia with a large dose of pentobarbital (55 mg/kg, i.p.) caused a sustained decrease in brain temperature (Tb), which was monitored with a probe placed in the midbrain reticular formation. The administration of TRH to the lateral ventricle antagonized this hypothermia. None of the acute surgeries examined in this paper (adrenal-demedullectomy, septal knife cuts, electrolytic lesions of the hypothalamus and midbrain knife cuts) had any essential effect on this antagonism by TRH. These results suggest that centrally-administered TRH exerts its effect on thermoregulation, at least in part, through brain structure(s) caudal to the midbrain.     

A novel class (H3) of histamine receptors on perivascular nerve terminals

Two types of histamine receptor, the H1- and H2-receptors, are found not only on vascular smooth muscle cells but on the perivascular autonomic nerve terminals. Activation of the prejunctional histamine receptors modifies transmitter release from the nerve terminals. Recently, histamine was shown to inhibit its own release from depolarized slices of rat cerebral cortex. This phenomenon was found to be mediated by a novel class of histamine receptor, the H3-receptor, that was pharmacologically distinct from the H1- and H2-receptors. Up to now, there has been no indication whether this third class of histamine receptor is present in any tissue other than the brain. We report here that histamine depresses sympathetic neurotransmission in the guinea-pig mesenteric artery by interacting with histamine H3-receptors on the perivascular nerve terminals. The pharmacological properties of these receptors are similar to those reported for the H3-receptors in the brain. Our data provide evidence for the existence of H3-receptors in the autonomic nervous system.     

Intraperitoneal growth pattern of murine teratocarcinomas

Summary Ascitic teratocarcinomas showed a unique growth pattern, suggesting size regulation in the peritoneal cavity of syngeneic 129/Sv mice.     

Reductive evolution suggested from the complete genome sequence of a plant-pathogenic phytoplasma

The minimal gene set essential for life has long been sought. We report the 860-kb genome of the obligate intracellular plant pathogen phytoplasma (Candidatus Phytoplasma asteris, OY strain). The phytoplasma genome encodes even fewer metabolic functions than do mycoplasma genomes. It lacks the pentose phosphate cycle and, more unexpectedly, ATP-synthase subunits, which are thought to be essential for life. This may be the result of reductive evolution as a consequence of life as an intracellular parasite in a nutrient-rich environment.     

Aging clock: the watchmaker’s masterpiece

The phenomenon of cellular senescence has been known for almost four decades. Yet, until very recently, the molecular mechanisms that lead to senescence have been poorly understood. However, substantial progress has been made in the last few years toward identifying the pathways executing senescence. This r view focuses on two major advances in this field, the telomere aging clock theory and the cell cycle regulatory mechanisms in senescent cells. These recent studies indicate that cellular senescence is a highly elaborate and active process, which presumably works as an anti-oncogenic mechanism.     

Rapid and reversible shape changes of molecular crystals on photoirradiation

The development of actuators based on materials that reversibly change shape and/or size in response to external stimuli has attracted interest for some time. A particularly intriguing possibility is offered by light-responsive materials, which allow remote operation without the need for direct contact to the actuator. The photo-response of these materials is based on the photoisomerization of constituent molecules (typically trans-cis isomerization of azobenzene chromophores), which gives rise to molecular motions and thereby deforms the bulk material. This effect has been used to create light-deformable polymer films and gels, but the response of these systems is relatively slow. Here we report that molecular crystals based on diarylethene chromophores and with sizes ranging from 10 to 100 micrometres exhibit rapid and reversible macroscopic changes in shape and size induced by ultraviolet and visible light. We find that on exposure to ultraviolet light, a single crystal of 1,2-bis(2-ethyl-5-phenyl-3-thienyl)perfluorocyclopentene changes from a square shape to a lozenge shape, whereas a rectangular single crystal of 1,2-bis(5-methyl-2-phenyl-4-thiazolyl)perfluorocyclopentene contracts by about 5-7 per cent. The deformed crystals are thermally stable, and switch back to their original state on irradiation with visible light. We find that our crystals respond in about 25 microseconds (that is, about five orders of magnitude faster than the response time of the azobenzene-based polymer systems) and that they can move microscopic objects, making them promising materials for possible light-driven actuator applications.