Elevation of Ammonia Contents in the Cerebral Hemisphere under the Blood-Brain Barrier Opening

Elevation of ammonia contents was observed 1 hr following infusion of 4% ammonium acetate only in the cerebral hemisphere where reversible opening of the blood-brain barrier was induced by intracarotid injection of 0.1% deoxycholic acid. This finding suggests that ammonia may contribute to hepatic encephalopathy, when the permeability of the blood-brain barrier is altered

Bile Acid and Ammonia-Induced Brain Edema in Rats

Infusion of bile acid such as chenodeoxycholic acid or deoxycholic acid through the carotid artery of rats produced reversible and unilateral opening of the blood-brain barrier without any tissue damage. Intravenous drip infusion of ammonium acetate during the opening resulted in severe edema of the brain. The results suggest the importance of bile acid and ammonia for the pathogenesis of brain edema frequently observed in acute hepatic failure

Acute optogenetic silencing of orexin/hypocretin neurons induces slow wave sleep in mice

Orexin/hypocretin neurons have a crucial role in the regulation of sleep and wakefulness. To help determine how these neurons promote wakefulness, we generated transgenic mice in which orexin neurons expressed halorhodopsin (orexin/Halo mice), an orange light-activated neuronal silencer. Slice patch-clamp recordings of orexin neurons that expressed halorhodopsin demonstrated that orange light photic illumination immediately hyperpolarized membrane potential and inhibited orexin neuron discharge in proportion to illumination intensity. Acute silencing of orexin neurons in vivo during the day (the inactive period) induced synchronization of the electroencephalogram and a reduction in amplitude of the electromyogram that is characteristic of slow-wave sleep (SWS). In contrast, orexin neuron photoinhibition was ineffective during the night (active period). Acute photoinhibition of orexin neurons during the day in orexin/Halo mice also reduced discharge of neurons in an orexin terminal field, the dorsal raphe (DR) nucleus. However, serotonergic DR neurons exhibited normal discharge rates in mice lacking orexin neurons. Thus, although usually highly dependent on orexin neuronal activity, serotonergic DR neuronal activity can be regulated appropriately in the chronic absence of orexin input. Together, these results demonstrate that acute inhibition of orexin neurons results in time-of-day-dependent induction of SWS and in reduced firing rate of neurons in an efferent projection site thought to be involved in arousal state regulation. The results presented here advance our understanding of the role of orexin neurons in the regulation of sleep/wakefulness and may be relevant to the mechanisms that underlie symptom progression in narcolepsy.National Institutes of Health (U.S.) (Grant R01NS057464

Intermediate-Mass-Elements in Young Supernova Remnants Reveal Neutron Star Kicks by Asymmetric Explosions

The birth properties of neutron stars yield important information on the still debated physical processes that trigger the explosion and on intrinsic neutron-star physics. These properties include the high space velocities of young neutron stars with average values of several 100 km/s, whose underlying "kick" mechanism is not finally clarified. There are two competing possibilities that could accelerate NSs during their birth: anisotropic ejection of either stellar debris or neutrinos. We here present new evidence from X-ray measurements that chemical elements between silicon and calcium in six young gaseous supernova remnants are preferentially expelled opposite to the direction of neutron star motion. There is no correlation between the kick velocities and magnetic field strengths of these neutron stars. Our results support a hydrodynamic origin of neutron-star kicks connected to asymmetric explosive mass ejection, and they conflict with neutron-star acceleration scenarios that invoke anisotropic neutrino emission caused by particle and nuclear physics in combination with very strong neutron-star magnetic fields.Comment: 24 pages, 12 figures, accepted for publication in The Astrophysical Journa

Spermatic Cord Lymphoma: A Case Report and Literature Review

Spermatic cord lymphoma is a rare lethal disease. It has a poor prognosis even in stage I or II disease when treated locally, therefore, multidisciplinary treatment for early stage is recommended. On the other hand, the treatment of choice for stage III or IV spermatic cord lymphoma remains to be determined. It is said that spermatic cord lymphoma is clinicopathologically similar to primary testicular lymphoma, therefore the treatment of spermatic cord lymphoma has often been determined by reference to the recommended treatment for primary testicular lymphoma. Here we report a new case of spermatic cord lymphoma, which was found in stage IV disease. We also review thirty-three cases which have been reported as spermatic cord lymphoma to date, and discuss treatment options

Transcriptionally linked simultaneous overexpression of P450 genes for broad-spectrum herbicide resistance

雑草が獲得した最強の除草剤抵抗性メカニズムの解明 --解毒酵素の一斉活性化--. 京都大学プレスリリース. 2023-06-14.Broad-spectrum herbicide resistance (BSHR), often linked to weeds with metabolism-based herbicide resistance, poses a threat to food production. Past studies have revealed that overexpression of catalytically promiscuous enzymes explains BSHR in some weeds; however, the mechanism of BSHR expression remains poorly understood. Here, we investigated the molecular basis of high-level resistance to diclofop-methyl in BSHR late watergrass (Echinochloa phyllopogon) found in the United States, which cannot be solely explained by the overexpression of promiscuous cytochrome P450 monooxygenases CYP81A12/21. The BSHR late watergrass line rapidly produced 2 distinct hydroxylated diclofop acids, only 1 of which was the major metabolite produced by CYP81A12/21. RNA-seq and subsequent reverse transcription quantitative PCR (RT-qPCR)-based segregation screening identified the transcriptionally linked overexpression of a gene, CYP709C69, with CYP81A12/21 in the BSHR line. The gene conferred diclofop-methyl resistance in plants and produced another hydroxylated diclofop acid in yeast (Saccharomyces cerevisiae). Unlike CYP81A12/21, CYP709C69 showed no other herbicide-metabolizing function except for a presumed clomazone-activating function. The overexpression of the 3 herbicide-metabolizing genes was also identified in another BSHR late watergrass in Japan, suggesting a convergence of BSHR evolution at the molecular level. Synteny analysis of the P450 genes implied that they are located at mutually independent loci, which supports the idea that a single trans-element regulates the 3 genes. We propose that transcriptionally linked simultaneous overexpression of herbicide-metabolizing genes enhances and broadens the metabolic resistance in weeds. The convergence of the complex mechanism in BSHR late watergrass from 2 countries suggests that BSHR evolved through co-opting a conserved gene regulatory system in late watergrass