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Neuropeptides may exert trophic effects during development, and then neurotransmitter roles in the developed nervous system. One way to associate peptide‐deficiency phenotypes with either role is first to assess potential phenotypes in so‐called constitutive knockout mice, and then proceed to specify, regionally and temporally, where and when neuropeptide expression is required to prevent these phenotypes. We have previously demonstrated that the well‐known constellation of behavioral and metabolic phenotypes associated with constitutive pituitary adenylate cyclase‐activating peptide (PACAP) knockout mice are accompanied by transcriptomic alterations of two types: those that distinguish the PACAP‐null phenotype from wild‐type (WT) in otherwise quiescent mice (cPRGs), and gene induction that occurs in response to acute environmental perturbation in WT mice that do not occur in knockout mice (aPRGs). Comparing constitutive PACAP knockout mice to a variety of temporally and regionally specific PACAP knockouts, we show that the prominent hyperlocomotor phenotype is a consequence of early loss of PACAP expression, is associated with Fos overexpression in hippocampus and basal ganglia, and that a thermoregulatory effect previously shown to be mediated by PACAP‐expressing neurons of medial preoptic hypothalamus is independent of PACAP expression in those neurons in adult mice. In contrast, PACAP dependence of weight loss/hypophagia triggered by restraint stress, seen in constitutive PACAP knockout mice, is phenocopied in mice in which PACAP is deleted after neuronal differentiation. Our results imply that PACAP has a prominent role as a trophic factor early in development determining global central nervous system characteristics, and in addition a second, discrete set of functions as a neurotransmitter in the fully developed nervous system that support physiological and psychological responses to stress. [ABSTRACT FROM AUTHOR]

Despite extensive research, the rewarding effects of cannabinoids are still debated. Here, we used a newly established animal procedure called optogenetic intracranial self-stimulation (ICSS) (oICSS) to re-examine the abuse potential of cannabinoids in mice. A specific adeno-associated viral vector carrying a channelrhodopsin gene was microinjected into the ventral tegmental area (VTA) to express light-sensitive channelrhodopsin in dopamine (DA) neurons of transgenic dopamine transporter (DAT)-Cre mice. Optogenetic stimulation of VTA DA neurons was highly reinforcing and produced a classical "sigmoidal"-shaped stimulation-response curve dependent upon the laser pulse frequency. Systemic administration of cocaine dose-dependently enhanced oICSS and shifted stimulation-response curves upward, in a way similar to previously observed effects of cocaine on electrical ICSS. In contrast, Δ9 -tetrahydrocannabinol (Δ9 -THC), but not cannabidiol, dose-dependently decreased oICSS responding and shifted oICSS curves downward. WIN55,212-2 and ACEA, two synthetic cannabinoids often used in laboratory settings, also produced dose-dependent reductions in oICSS. We then examined several new synthetic cannabinoids, which are used recreationally. XLR-11 produced a cocaine-like increase, AM-2201 produced a Δ9 -THC-like reduction, while 5F-AMB had no effect on oICSS responding. Immunohistochemistry and RNAscope in situ hybridization assays indicated that CB1 Rs are expressed mainly in VTA GABA and glutamate neurons, while CB2 Rs are expressed mainly in VTA DA neurons. Together, these findings suggest that most cannabinoids are not reward enhancing, but rather reward attenuating or aversive in mice. Activation of CB1 R and/or CB2 R in different populations of neurons in the brain may underlie the observed actions. [ABSTRACT FROM AUTHOR]

We have recently reported the expression of functional cannabinoid CB2 receptors (CB2 Rs) in midbrain dopamine (DA) neurons in mice. However, little is known whether CB2 Rs are similarly expressed in rat brain because significant species differences in CB2 R structures and expression are found. In situ hybridization and immunohistochemical assays detected CB2 gene and receptors in DA neurons of the ventral tegmental area (VTA), which was up-regulated in cocaine self-administration rats. Electrophysiological studies demonstrated that activation of CB2 Rs by JWH133 inhibited VTA DA neuronal firing in single dissociated neurons. Systemic administration of JWH133 failed to alter, while local administration of JWH133 into the nucleus accumbens inhibited cocaine-enhanced extracellular DA and i.v. cocaine self-administration. This effect was blocked by AM630, a selective CB2 R antagonist. These data suggest that CB2 Rs are expressed in VTA DA neurons and functionally modulate DA neuronal activities and cocaine self-administration behavior in rats. [ABSTRACT FROM AUTHOR]

Summary: Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic haematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients receiving haploidentical HSCT (haplo‐HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo‐HSCT patients. From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo‐HSCT at Peking University Institute of Haematology were screened for HEV using HEV serology. HEV RNA was assessed in blood samples when HEV‐IgG and/or IgM antibodies were positive. Acute HEV infection was identified in 7 patients (3·9%), 1 of whom had developed a chronic HEV infection. The median time from haplo‐HSCT to HEV infection was 17·5 (range, 6–55) months. HEV infection was confirmed by the presentation of anti‐HEV IgM + anti‐HEV IgG (rising) (n = 5) or HEV‐RNA + anti‐HEV IgM + anti‐HEV IgG (n = 2). None of the patients died of HEV infection directly: 2 patients with HEV infection died showing signs of ongoing hepatitis, and 5 patients cleared HEV with a median duration of HEV infection of 1·5 (range, 1·0–5·7) months. In conclusion, HEV infection is a rare but serious complication after haplo‐HSCT. We recommend screening of HEV in haplo‐HSCT. [ABSTRACT FROM AUTHOR]

ABSTRACT This work has obtained polyaniline/manganese dioxide (PANI/MnO2) nanofibers microsphere by interfacial chemical synthesis with 4-amino-thiophenol (4-ATP) as the structure-directing agent on the Au substrate. The cyclic voltammograms, galvanostatic charge-discharge, and electrochemical impedance spectroscopy were used to determine their capacitive performance. Powder X-ray diffraction, thermogravimetry and differential scanning calorimetry, Fourier transformed infrared spectroscopy, Brunauer-Emmett-Teller surface area measurements, and scanning electron microscope were performed for physical and chemical characterization. The effect of 4-ATP and acids on the capacitive performance of PANI/MnO2 nanofibers microsphere was elucidated. The as-prepared PANI/MnO2 was nanofiber about 30 nm diameters, and they further self-assembled into sphere. Its specific capacitance is up to 765 F g−1 at 1.0 mA cm−2 in 1.0 M Na2SO4 solution. And it shows a high stability with a capacitance fade of only 14.9% after 400 charge-discharge cycles. The symmetric capacitor of PANI/MnO2 (PM10+)/PANI/MnO2 (PM10−) is assembled in 1.0 M Na2SO4 solution, and its capacitive performance is compared with that of PANI (+)/PANI (−) and MnO2 (+)/MnO2 (−). © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40575. [ABSTRACT FROM AUTHOR]

Pre-clinical studies suggest that negative allosteric modulators ( NAMs) of the metabotropic glutamate receptor subtype 5 ( mGluR5), including 2-methyl-6-(phenylethynyl)pyridine ( MPEP), 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine ( MTEP) and fenobam are highly effective in attenuating drug-taking and drug-seeking behaviors. However, both MPEP and MTEP have no translational potential for use in humans because of their off-target effects and short half-lives. Here, we report that 3-fluoro-5-[(6-methylpyridin-2-yl)ethynyl]benzonitrile ( MFZ 10-7), a novel mGluR5 NAM, is more potent and selective than MPEP, MTEP and fenobam in both in vitro binding and functional assays. Similar to MTEP, intraperitoneal administration of MFZ 10-7 inhibited intravenous cocaine self-administration, cocaine-induced reinstatement of drug-seeking behavior and cocaine-associated cue-induced cocaine-seeking behavior in rats. Although MFZ 10-7 and MTEP lowered the rate of oral sucrose self-administration, they did not alter total sucrose intake. Further, MFZ 10-7 appeared to be more potent than MTEP in inducing downward shifts in the cocaine dose-response curve, but less effective than MTEP in attenuating sucrose-induced reinstatement of sucrose-seeking behavior. MFZ 10-7 and MTEP had no effect on basal locomotor behavior. These findings not only provide additional evidence supporting an important role for mGluR5 in cocaine reward and addiction, but also introduce a new tool for both in vitro and in vivo investigations with which to further characterize this role. [ABSTRACT FROM AUTHOR]

The selectivities to pathogenic Klebsiella strains of different isolation media were compared by known standard strains. The modified MacConkey-inositol-carbenicillin (MCIC) medium (Named MCIAC, MacConkey-inositol-adonitol-carbenicillin) supplemented with adonitol gave no false-negative colonies, and exhibited higher selectivity. MCIC and Simmons citrate agar with inositol (SCAI) media gave two false-negative colonies, respectively. These three media all gave two false-positive colonies, respectively. Salmonella Shigella medium gave four false-negative colonies and five false-positive colonies. Violet red bile glucose agar medium gave the most false-positive colonies, although it gave no false-negative colonies. One hundred samples of powdered milk were examined by MCIAC, MCIC and SCAI plates. The typical positive colonies were further identified using Vitek GNI Auto Microbic system and API 20E system. The results showed that the specificity of the MCIAC medium was higher than MCIC and SCAI media. PRACTICAL APPLICATIONS MacConkey-inositol-carbenicillin (MCIC) is the most commonly used selective medium for the detection of Klebsiella. But some inositol-nonfermenting Klebsiella strains would be missed when selected by this medium. We improved the MCIC medium by supplementing with 1% adonitol. The new modified medium (MacConkey-inositol-adonitol-carbenicillin, MCIAC) had advantages over other selective Klebsiella media in having a higher selectivity and an incubation time of only 16–24 h. MCIAC could be routinely used for pathogenic Klebsiella selection of powdered milk and other food samples. [ABSTRACT FROM AUTHOR]

Abstract: β-Amyloid protein (Aβ), a major protein component of brain senile plaques in Alzheimer''s disease, is known to be directly responsible for the production of reactive oxygen species (ROS) and induction of apoptosis. In this study, the protective effect of puerarin, an isoflavone purified from the radix of the Chinese herb Pueraria lobata, on Aβ-induced rat pheochromocytoma (PC12) cultures was investigated. Although exposure of PC12 cells to 50μM Aβ25–35 caused significant viability loss and apoptotic rate increase, pretreatment of the cells with puerarin for 24h reduced the viability loss and apoptotic rate. Puerarin (1μM) significantly inhibited Aβ25–35-induced apoptosis of PC12 cells. Preincubation of the cell with puerarin also restored the ROS and mitochondrial membrane potential levels that had been altered as a result of Aβ25–35 treatment. Puerarin was also found to increase the Bcl-2/Bax ratio and reduce caspase-3 activation. These results suggest that puerarin could attenuate Aβ25–35-induced PC12 cell injure and apoptosis and could also promote the survival of PC12 cells. Therefore, puerarin may act as an intracellular ROS scavenger, and its antioxidant properties may protect against Aβ25–35-induced cell injury. [Copyright &y& Elsevier]

Fusion of the egg and the sperm cells in plants produces a zygote that develops into an embryo. Screening of ethyl methanesulfonate-mutagenized populations of Arabidopsis led to the identification ofEMBRYONIC FACTOR 1(FAC1), a locus that gives a zygote-lethal phenotype when mutated. TheFAC1gene was identified by positional cloning and confirmed by a genetic complementation test against a T-DNA insertion allele. It encodes an AMP deaminase (AMPD) that is known in human and yeast to convert AMP to IMP to maintain the energy potential. Expression ofFAC1in a yeastAMPDmutant after removal of its N-terminal putative transmembrane domain complemented the mutant phenotype, suggesting a functional conservancy but a structural divergence through evolution. Although a low level ofFAC1expression was observed in all organs tested, using a reporter construct we observed a significantly increasedFAC1expression in the zygote, early embryo and endosperm. Furthermore, during somatic embryogenesis, a high level ofFAC1expression was observed in developing embryos including putative embryogenic cells.FAC1, therefore, represents one of the earliest expressed genes known in plants. It may act through AMP depletion to provide sufficient energy for the zygote to proceed through development. [ABSTRACT FROM AUTHOR]

Zhang H-Y, Nanji AA, Luk JM, Huang X-R, Lo C-M, Chen YX, Yuen S-T, Lan HY, Lau GKK. Macrophage migration inhibitory factor expression correlates with inflammatory changes in human chronic hepatitis B infection.Liver International: 2005: 25: 571–579.© Blackwell Munksgaard 2005Macrophage migration inhibitory factor (MIF) has emerged to be a pivotal cytokine in immune-mediated diseases.To investigate the role of MIF in chronic hepatitis B infection, we studied two groups of hepatitis B surface antigen positive patients: group 1 (immune tolerant,n=16) and group 2 (immune clearance,n=16). Serum level of MIF was measured by enzyme-linked immunosorbent assay and intrahepatic expression of MIF, macrophage and T-cell localisation were detected by double immunohistochemistry.An increased serum MIF correlated significantly with increased serum alanine aminotransferase activity (r=0.73,P<0.001) and the severity of necroinflammatory injury (r=0.642,P<0.001). In group 2, there was marked MIF mRNA expression in all KP-1+ macrophages and CD45RO+ activated T cells and, to a lesser extent, in hepatocytes within inflammatory areas. In contrast to its mRNA expression, the cytoplasmic MIF protein level in hepatocytes, infiltrating macrophages and T cells within the inflammatory area was reduced, which probably contributed to the increased serum MIF level.Our data suggested that MIF played a role in sustaining cell-mediated hepatic injury during the immune-clearance phase of chronic hepatitis B infection. [ABSTRACT FROM AUTHOR]

We have recently reported the expression of functional cannabinoid CB 2 receptors (CB 2 Rs) in midbrain dopamine (DA) neurons in mice. However, little is known whether CB 2 Rs are similarly expressed in rat brain because significant species differences in CB 2 R structures and expression are found. In situ hybridization and immunohistochemical assays detected CB 2 gene and receptors in DA neurons of the ventral tegmental area (VTA), which was up-regulated in cocaine self-administration rats. Electrophysiological studies demonstrated that activation of CB 2 Rs by JWH133 inhibited VTA DA neuronal firing in single dissociated neurons. Systemic administration of JWH133 failed to alter, while local administration of JWH133 into the nucleus accumbens inhibited cocaine-enhanced extracellular DA and i.v. cocaine self-administration. This effect was blocked by AM630, a selective CB 2 R antagonist. These data suggest that CB 2 Rs are expressed in VTA DA neurons and functionally modulate DA neuronal activities and cocaine self-administration behavior in rats., (© 2016 Society for the Study of Addiction.)