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Late blight and powdery mildew are two widespread tomato diseases caused by Phytophthora infestans and Oidium neolycopersici, respectively, which reduce the quantity and quality of tomato. MicroRNAs (miRNAs) play critical roles in tomato resistance to various pathogens. Investigating the function of miRNAs is of great significance in controlling tomato diseases. To identify potential miRNAs involved in the interaction of tomato with P. infestans or O. neolycopersici, we analyzed the expression profiles of small RNAs in tomato leaves infected with these two pathogens using RNA-seq technology. A total of 330 and 288 miRNAs exhibited differences in expression levels after exposure to P. infestans and O. neolycopersici, respectively. One hundred and forty-six commonly differentially expressed (DE) miRNAs responsive to P. infestans and O. neolycopersici infestation were detected, including 10 commonly known conserved DE miRNAs and 136 novel miRNAs. Among these known DE miRNAs, sly-miR397 was strongly downregulated in response to P. infestans or O. neolycopersici infection. Silencing of sly-miR397 resulted in enhanced tolerance to the pathogens, whereas overexpression of sly-miR397 showed increased susceptibility. Furthermore, changes in sly-miR397 expression could also affect expression levels of pathogenesis-related genes and reactive oxygen species-scavenging genes, leading to altered necrotic cells and H2O2 levels. In addition, the number of lateral branches significantly changed in transgenic plants. Taken together, our results provide potential miRNA resources for further research of miRNA-disease associations and indicates that sly-miR397 acts as a negative regulator of disease resistance and influences lateral branch development in tomato.

Chemodynamic therapy when combined with chemotherapy opens up a new avenue for treatment of cancer. However, its development is still restricted by low targeting, high dose and toxic side effects. Herein, rational designing and construction of a new multifunctional platform with the core-shell structure 5-ALA@UiO-66-NH-FAM@CP1 (ALA = 5-aminolevulinic acid, CP1 = zirconium-pemetrexed (Zr-MTA)) has been performed. In this platform, CP1 acting as a shell is encapsulated with the UiO-66-NH

Two new coordination polymers (CPs), namely [Cd2(L)(2,2′-bipy)] (1) and [Cd2(L)(H2O)4] (2) (H4L = [1,1′-biphenyl]-2,3,3′,5′-tetracarboxylic acid and 2,2′-bipy = 2,2′-bipyridine), have been successfully synthesized under solvothermal conditions. 1 exhibits a 2D layer that was further extended into a 3D supramolecular framework through the packing interaction. 2 has a 3D 3,3,4-c network with a point symbol of (62·82)(63)2. The sensing results illustrated that both of them could be prospective candidates for developing luminescent sensors for the probing of Fe3+ and CrO42−. The probe effects remained highly selective to the Fe3+ and CrO42− ions even if there are other interfering ions. The limits of detection (LODs) for Fe3+/CrO42− were calculated to be ca. 2.47 × 10−8 M−1/1.12 × 10−8 M−1 and 1.35 × 10−9 M−1/2.23 × 10−8 M−1 for 1 and 2, respectively. The fluorescence resonance energy transfer process may be the major pathway behind the quenching mechanism for Fe3+ and CrO42- ions. The recycling operation indicated that compounds 1 and 2 are promising reusable probes for their effective capability of detecting Fe3+ and CrO42− ions.

With increasing pathogenic bacterial infection that is occurring worldwide, antibacterial therapy has become an important research field. There is great antimicrobial potential in the nanomaterial-based metal–organic framework (MOF) platform because it is highly biocompatible, biodegradable, and nontoxic, and it is now widely used in the anticancer agent industry and in the production of medical products. This review summarizes the possible mechanisms of representative MOF-based nanomaterials, and recounts recent progress in the design and development of MOF-based antibacterial materials for the remedy of postoperative infection. The existing shortcomings and future perspectives of the rapidly growing field of antimicrobial therapy addressing patient quality of life issues are also briefly discussed. Because of their wide applicability, further studies on the use of different MOF antimicrobial therapies will be of great interest.

Olfactory imagery (OI) is defined as the generation of odour images in the mind. There are large inter-individual differences regarding OI abilities. However, the neural representations of OI among individuals with high or low OI abilities are less understood. Participants with high or low OI abilities evaluated using the Vividness of Olfactory Imagery Questionnaire were recruited in this study. Brain activations were measured during a word cueing OI and visual imagery (VI) tasks using functional magnetic resonance imaging (fMRI). In addition, the OI task was divided into two parts. In one part, OI was performed for 8 s (long imagery generation time) and in the other part for 2 s (short imagery generation time). Ratings of the overall imagery vividness were collected at the end of each task. The vividness of OI during short OI was lower among participants with low OI abilities compared to participants with high OI abilities. Brain imaging results showed that participants with low OI ability had stronger brain activation of the supplementary motor area and the superior frontal cortex, compared to participants with higher OI abilities during the short versus long imagery generation time conditions. These results suggest that when generating odour images in a relatively short period of time (e.g., 2 s), people with either high or low OI abilities may have adopted different approaches, resulting in diverse brain activation.

During cochlear development, the Notch ligand JAGGED 1 (JAG1) plays an important role in the specification of the prosensory region, which gives rise to sound-sensing hair cells and neighboring supporting cells (SCs). While JAG1's expression is maintained in SCs through adulthood, the function of JAG1 in SC development is unknown. Here, we demonstrate that JAG1 is essential for the formation and maintenance of Hensen's cells, a highly specialized SC subtype located at the edge of the auditory epithelium. UsingSox2CreERT2/+::Jag1loxP/loxPmice of both genders, we show thatJag1deletion at the onset of differentiation, at embryonic day 14.5, disrupted Hensen's cell formation. Similar loss of Hensen's cells was observed whenJag1was deleted after Hensen's cell formation at postnatal day (P) 0/P1 and fate-mapping analysis revealed that in the absence ofJag1, some Hensen's cells die, but others convert into neighboring Claudius cells. In support of a role for JAG1 in cell survival, genes involved in mitochondrial function and protein synthesis were downregulated in the sensory epithelium of P0 cochlea lackingJag1. Finally, usingFgfr3-iCreERT2::Jag1loxP/loxPmice to deleteJag1at P0, we observed a similar loss of Hensen's cells and found that adultJag1mutant mice have hearing deficits at the low-frequency range.SIGNIFICANCE STATEMENTHensen's cells play an essential role in the development and homeostasis of the cochlea. Defects in the biophysical or functional properties of Hensen's cells have been linked to auditory dysfunction and hearing loss. Despite their importance, surprisingly little is known about the molecular mechanisms that guide their development. Morphologic and fate-mapping analyses in our study revealed that, in the absence of the Notch ligand JAGGED1, Hensen's cells died or converted into Claudius cells, which are specialized epithelium-like cells outside the sensory epithelium. Confirming a link between JAGGED1 and cell survival, transcriptional profiling showed that JAGGED1 maintains genes critical for mitochondrial function and tissue homeostasis. Finally, auditory phenotyping revealed that JAGGED1's function in supporting cells is necessary for low-frequency hearing.

Imagery vividness is one of the key indicators to evaluate the ability to generate mental images. There is large inter-individual variability in olfactory imagery (OI) abilities, however, little is known about the underlying factors for individual OI abilities. Using a word cueing imagery paradigm and the trial-by-trial imagery vividness rating method, participants with high or low OI abilities (differentiated by the Vividness of Olfactory Imagery Questionnaire) completed two OI tasks with either shorter (2 s) or longer (8 s) image generation time. Participants' olfactory function, olfactory-related working memory and episodic recognition memory were measured using validated methods. Moreover, olfactory metacognition was assessed using the Odor Awareness Scale (OAS) and the Importance of Olfaction Questionnaire (IOQ). Compared to participants with high OI abilities, those with low OI abilities reported less vivid odor images during OI tasks. For participants with low OI abilities, the imagery vividness significantly improved as the image generation time increased. There was no difference regarding olfactory perception or olfactory-related memory performances between the high and the low OI ability groups. However, participants with higher OI abilities had significant higher scores on the OAS and the IOQ, indicating a superior olfactory-related metacognition. These results provide evidences supporting the underlying factors that related to variances of subjective ability of generating vivid odor mental images.

During cochlear development, the Notch ligand JAGGED 1 (JAG1) plays an important role in the specification of the prosensory region, which gives rise to sound-sensing hair cells and neighboring supporting cells (SCs). While JAG1’s expression is maintained in SCs through adulthood, the function of JAG1 in SC development is unknown. Here, we demonstrate that JAG1 is essential for the formation and maintenance of Hensen cells (HeCs), a highly specialized SC-subtype located at the edge of the auditory epithelium. Deletion ofJag1at the onset of differentiation, at stage E14.5, disrupted HeC formation. Similar loss of HeCs was observed whenJag1was deleted at P0/P1 and fate-mapping analysis revealed that in the absence ofJag1some HeCs die, but others convert into neighboring Claudius cells. In support of a role for JAG1 in cell survival, genes involved in mitochondrial function and protein synthesis were downregulated in P0 cochlea lackingJag1.

Coordination polymers (CPs) are peculiar class of multidimensional materials which can be employed as photocatalytic materials to decompose lethal aromatic dyes present in waste-water discharge. Herein, four new Zn(II)/Cd(II) coordination polymers (CPs) namely [Cd2(H2O)(H3L)2(2,2′-bipy)2]·H2O (1), [Zn2(HL)(H2O)2(2,2′-bipy)2]·H2O (2), [Cd2(HL)(bmb)0.5(H2O)]·2H2O (3) and [Zn4(L)2(bpz)4·H2bpz]·4H2O (4) (H5L = 3,5-bis(3,4-dicarboxylphenoxy)benzoic acid, 2,2′-bipy = 2,2′-bipyridine, bmb = 1,4-bis(2-methylimidazol-1-yl)butane, bpz = 3,3′,5,5′-tetramethyl-4,4′-bipyrazole), have been synthesized solvothermally and characterized. The single crystal X-ray diffraction reveals that CPs 1 and 2 exhibit 2D supramolecular framework built by the hydrogen bond interactions between adjacent chains. The CP 3 features a 2D double layer while 4 display 3D 3,3,4,4-connected topology with point symbol {4.6.84}{4.6.8}{62.84}{62.8}. All these newly synthesized materials exhibit photocatalytic properties and the results demonstrated that they exhibit efficient photocatalytic performances to selectively degrade methylene blue (MB) among the dyes viz. methylene orange (MO), acid orange (AO), congo red (CR) and acid chrome blue (ACB) under UV irradiation. A mechanistic investigation toward better understanding of the photocatalytic degradation of MB has been carried out using LC-MS studies. Also computational investigation by performing band gap calculations have been accomplished to address the probable mechanistic pathway which further have been assisted with Hirshfeld surface analysis.

Two 2D Cd(II)/Co(II)-based polymers derived from 1-(3,4-dicarboxylphenyl)-4-(5-carboxy-1H-benzimidazol-2-yl) benzene (H3L), namely, [Cd3(H2O)(L)2(phen)2·7H2O] (1) and [Co3(H2O)2(L)2(2,2′-bipy)2·3H2O] (2), have been obtained and characterized. Compound 1 shows a 3D supramolecular network through π···π interactions from the inter-layer phenanthrolines. While 2 has 1D chain construct by the integration of metal center and side substitution of the flexible tricarboxylate linker. Apart from this, the photocatalytic activity of the Cd-based CP 1 was also evaluated under UV light irradiation which revealed efficient photocatalytic activity (52.3%) for methylene blue (MB) degradation without the use of any enhancers. The major intermediate degradation products were authenticated by LC-MS methodology to speculate on their possible degradation mechanisms of MB.

Two new Zn(II) metal-organic-frameworks displaying supramolecular isomerism have been synthesized using 1,3-bis(2-methylimidazolyl)propane (bmp) and 1,3,5-benzenetricarboxylic acid (H3BTC). The isomer [NH2(CH3)2][Zn2O(bmp)(BTC)] (1) adopt 2-fold interpenetrating framework topology defined by bey-type of interpenetration while another isomer [NH2(CH3)2][Zn2O(bmp)(BTC)].1.5DMF (2) adopt 2-fold interpenetrating framework topology defined by CdSO4-type of interpenetration. The difference in topologies of two MOFs can be ascribed to the flexibility of 1,3-bis(2-methylimidazolyl)propane ligand; because of which 2 lies on a crystallographic mirror plane. Both MOFs display efficient photocatalytic properties for the photodegradation of model aromatic dye methyl violet (MV). The photocatalytic mechanism in both the MOFs have been explained by using density of states calculations. Moreover, chromatography-mass spectrometry (LC-MS) has been performed to further validate the potential photodegradation mechanism of MV.

Two new Cu(II)/Co(II) coordination polymer (CPs) namely, [Co2(H2O)2(L)2(2,2′-bipy)2·H2O] (1) and [Cu2(L)2(bbi)] (2) (H2L=3,3′-(1,2-phenylenebis(methyleneoxy)) dibenzoic acid, bbi = 1,1′-(1,4-butanediyl)bis(imidazole), 2,2,’-bipy=2,2,’-bipyridine), have been designed and synthesized. 1 has 1D helical structure built by the connectivity of Co atoms and phenolic-oxygen containing branches of the flexible dicarboxylate linkages, which was further form a 2D supramolecular sheet through the strong π···π stacking interactions and H-bonded interactions. 2 exhibits 2D layer constructed by the double [Cu4L2] chains and anti-conformational bbi ligands. The current results illustrated that the N-donor ligand may play a distinct effect in the formation of these mortifies. The photocatalytic performances to degrade methyl violet (MV) and Rhodamine B (Rh B) under UV irradiation were studied.

Previous studies have shown sex different patterns in behavioral responses to cocaine. Here, we used between-subject experiment design to study whether sex differences exist in the development of behavioral sensitization and tolerance to repeated cocaine, as well as the role of protein kinase A (PKA) signaling cascade in this process. Ambulatory and rearing responses were recorded in male and female rats after 1 to 14 days of administration of saline or cocaine (15 mg/kg; ip). Correspondent PKA-associated signaling in the nucleus accumbens (NAc) and caudate-putamen (CPu) was measured at each time point. Our results showed that females exhibited higher cocaine-induced behavioral responses and developed behavioral sensitization and tolerance faster than males. Whereas females developed behavioral sensitization to cocaine after 2 days and tolerance after 14 days, male rats developed sensitization after 5 days. In addition, cocaine induced a sexual dimorphic pattern in the progression of neuronal adaptations on the PKA cascade signaling in region (NAc vs. CPu) and time (days of cocaine administration)-dependent manners. In general, more PKA signaling cascade changes were found in the NAc of males on day 5 and in the CPu of females with repeated cocaine injection. In addition, in females, behavioral activities positively correlated with FosB levels in the NAc and CPu and negatively correlated with Cdk5 and p35 in the CPu, while no correlation was observed in males. Our studies suggest that repeated cocaine administration induced different patterns of behavioral and molecular responses in the PKA cascade in male and female rats.

Neuregulin 3 (NRG3) and ErbB4 have been linked to nicotine addiction; however, the neuronal mechanisms and behavioral consequences of NRG3–ErbB4 sensitivity to nicotine remain elusive. Recent literature suggests that relapse to smoking is due to a lack of impulsive control, which is thought to be due to altered functioning within the orbitofrontal cortex (OFC). Therefore, we examined circuitry changes within this structure following nicotine application. We report that nicotine controls synaptic plasticity in the OFC through NRG3/ErbB4-dependent regulation of GABAergic inhibition. We observed that both nicotine and NRG3 facilitated the conversion of long-term potentiation into long-term depression at cortical layer 3/5 synapses. Induction of long-term depression by nicotine relied on nicotinic receptor activation and key regulators of NRG3 signaling: (1) release of intracellular calcium, (2) activation of the BACE1 beta-secretase, and (3) ErbB4 receptor activation. Nicotine-induced synaptic plasticity was also associated with accumulation of intracellular GABA and was completely blocked by GABA(A)/GABA(B) antagonists. To test whether these mechanisms underlie OFC-dependent behavior, we evaluated the effects of nicotine in the go/no-go task. Nicotine-impaired stimulus discrimination in this task was rescued by pharmacologic disruption of the NRG3 receptor, ErbB4. Altogether, our data indicate that nicotine-induced synaptic plasticity in the OFC and cognitive changes depend on NRG3–ErbB4 signaling. We propose that nicotine activation of this pathway may contribute to nicotine addiction, particularly in individuals with genetic variation in NRG3.

Oxytocin has a modulatory role in natural and drug reward processes. While the role of oxytocin in pair bonding and reproduction has been extensively studied, sex differences in conditioned and unconditioned behavioral responses to oxytocin treatment have not been fully characterized. Here, we determined whether male and female rats would show similar dose response curves in response to acute oxytocin on measures of locomotor activity, sucrose seeking, and sucrose intake. Male and freely cycling female rats received vehicle or oxytocin (0.1, 0.3, 1, 3 mg/kg, IP) injections before behavioral tests designed to assess general motor activity, as well as sucrose self-administration and seeking. Lower doses of oxytocin decreased motor activity in a novel environment in females relative to males. Likewise, lower doses of oxytocin in females decreased responding for sucrose during maintenance of sucrose self-administration and reinstatement to sucrose-conditioned cues. However, sucrose seeking in response to a sucrose prime was only decreased by the highest oxytocin dose in both sexes. In general, oxytocin had similar effects in both sexes. However, females were more sensitive to lower doses of oxytocin than males. These findings are consistent with the notion that oxytocin regulates many of the same behaviors in males and females, but that the effects are typically more profound in females. Therapeutic use of oxytocin should include sex as a factor in determining dose regimens.

A selective and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for investigating the pharmacokinetics of umbelliferone, apigenin, genkwanin and hydroxygenkwanin after oral administration of Daphne genkwa extract. Plasma samples were treated by protein precipitation with acetonitrile. Analytes were detected by triple-quadrupole MS/MS with an ESI source in negative selection reaction monitoring mode. The transitions of m/z 161 → 133 for umbelliferone, m/z 269 → 117 for apigenin, m/z 283 → 268 for genkwanin and m/z 299 → 284 for hydroxygenkwanin were confirmed for quantification. Chromatographic separation was conducted using an Eclipse XDB-C18 column, and the applied isocratic elution program allowed for simultaneous determination of the four analytes for a total run time of 2.5 min. The linearity was validated over the plasma concentration ranges of 1.421-1421 ng/mL for umbelliferone, 0.845-845 ng/mL for apigenin, 1.025-1025 ng/mL for genkwanin and 0.845-845 ng/mL for hydroxygenkwanin. The extraction recovery rate was >82.7% for each analyte. No apparent matrix effect was observed during the bioanalysis. After full validation, the proposed method was successfully applied to compare the pharmacokinetics of these analytes between normal and arthritic rats.

Addiction to nicotine and the inability to quit smoking are influenced by genetic factors, emphasizing the importance of understanding how genes and drugs of abuse mechanistically impact each other. One well-characterized protein responsible for regulating both response to drugs and gene expression is the transcription factor CREB (cAMP-responsive element binding protein). Previous work indicates that hippocampal-specific alterations in CREB signaling and synaptic plasticity may underlie certain nicotine withdrawal phenotypes. However, the structure of the hippocampus possesses dorsal and ventral subregions, each differing in behavioral, anatomic and gene expression characteristics. This study examines the effects of CREB deletion specifically in the ventral or dorsal hippocampus of animals chronically treated with saline, nicotine, or undergoing 24 h withdrawal. After region-specific viral injections of AAV-GFP or AAV-CRE in CREBloxP/loxP animals, behavioral testing measured anxiety levels, using the Novelty-Induced Hypophagia test, and cognition, using a contextual fear conditioning paradigm. Deletion of CREB in the ventral, but not dorsal, hippocampus resulted in amelioration of nicotine withdrawal-induced anxiety-like behavior in the Novelty-Induced Hypophagia test. In contrast, CREB deletion in the dorsal hippocampus resulted in learning and memory deficits in fear conditioning, whereas CREB deletion in the ventral hippocampus showed an enhancement in learning. Gene expression analysis showed differential treatment- and region-dependent alterations of several CREB target genes that are well-known markers of neuroplasticity within the hippocampus. Collectively, these data provide persuasive evidence towards the distinct roles of CREB within the dorsal and ventral hippocampus separately in mediating select nicotine withdrawal phenotypes.

The orexin/hypocretin system has been implicated in multiple phases of drug addiction. Acute orexin receptor blockade with the orexin-1 receptor (OX1R) antagonist, SB-334867, has been found to reduce cocaine seeking after cocaine self-administration. As repeated drug dosing can have differential effects and is more clinically relevant than acute dosing, in the current study we examined the effects of repeated SB-334867 on cocaine self-administration, extinction, and reinstatement to cocaine seeking in Sprague–Dawley rats. We found that repeated SB-334867 (10 mg/kg/day) had no effect on established cocaine self-administration. Repeated SB-334867 (both 10 and 20 mg/kg) attenuated cocaine seeking during extinction; however, this effect was only observed when animals had no prior experience with SB-334867 and when SB-334867 was administered prior to, but not after, daily extinction sessions. Notably, daily treatment with SB-334867 (10 mg/kg) during extinction increased subsequent cue-induced reinstatement, whereas repeated SB-334867 (20 mg/kg) administration during extinction enabled acute SB-334867 to reduce cue-induced reinstatement. Repeated SB-334867 treatment (10 or 20 mg/kg) failed to affect reinstatement induced by priming injections of cocaine (10 mg/kg). These results show that repeated inhibition of OX1R-mediated signaling exerts a lasting and specific role in mediating environmentally activated cocaine seeking.

Withdrawal from cocaine regulates expression of distinct glutamate re-uptake transporters in the nucleus accumbens (NAc). In this study, we examined the cumulative effect of glutamate re-uptake by multiple excitatory amino acid transporters (EAATs) on drug-seeking at two different stages of withdrawal from self-administered cocaine. Rats were trained on fixed ratio 1 (FR1), progressing to FR5 schedule of reinforcement. After one day of withdrawal, microinfusion of a broad non-transportable EAAT antagonist, DL-threo-beta-benzyloxyaspartate (DL-TBOA), into the NAc shell dose-dependently attenuated self-administration of cocaine. Sucrose self-administration was not affected by DL-TBOA, indicating an effect specific to reinforcing properties of cocaine. The attenuating effect on cocaine seeking was not due to suppression of locomotor response, as DL-TBOA was found to transiently increase spontaneous locomotor activity. Previous studies have established a role for EAAT2-mediated re-uptake on reinstatement of cocaine seeking following extended withdrawal and extinction training. We found that blockade of NAc shell EAATs did not affect cocaine-primed reinstatement of cocaine seeking. These results indicate that behavioral history of withdrawal influences the effect of re-uptake mediated glutamate clearance on cocaine seeking. Dynamic regulation of glutamate availability by re-uptake mechanisms may impact other glutamate signaling pathways to account for such differences.

Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin's impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin's attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin's effect on cocaine seeking may be mediated by different mechanisms in male and females.

Alterations in protein kinase (PKA) protein levels have been implicated in the regulation of responses to and development of cocaine addiction. However, the contribution of differences in PKA intracellular cascade to the known sex differences in responses to cocaine is not well understood. This study examined whether there are intrinsic or cocaine-induced alterations in PKA-mediated responses, such as phosphorylation of cyclic AMP response element binding protein, in male and female rats. To this end, protein levels of PKA and phosphorylated CREB (pCREB) in the caudate putamen (CPu) and nucleus accumbens (NAc) of male and female rats were measured basally or after acute (one 30-mg/kg intraperitoneal injection) or chronic (twice-daily 15-mg/kg injections for 14 days) cocaine administration. Behavioral responses to both cocaine administration paradigms were also studied. Similar to previous findings, ambulatory, rearing, and stereotypic activities were higher in female rats after acute cocaine administration. Sex differences in cocaine-induced responses were also observed after chronic cocaine administration: While males developed a robust sensitization in ambulatory activities to cocaine, females developed tolerance in cocaine-induced rearing and stereotypic activities. In the basal group, females had significantly higher PKA protein levels in the NAc. Regardless of the cocaine administration paradigm, PKA protein levels in the NAc were higher overall in females than in males. Furthermore, after cocaine administration, while pCREB protein levels in male rats were induced for a longer amount of time than in female rats, the magnitude of change on pCREB levels were higher in female than male rats. However, in the CPu, no sex differences in PKA or pCREB protein levels were observed either in the basal group or after acute or chronic cocaine administration. Taken together, these findings suggest that sex differences in basal and cocaine-induced alterations in the PKA signaling regulation in the NAc may contribute to sex differences in the psychomotor responses to cocaine.

Activation of extracellular signal-regulated kinase (ERK) and dopamine- and cAMP-regulated phosphoprotein (DARPP-32) pathways has been implicated in biochemical and behavioral effects induced by various drugs of abuse. In this study, we investigated the phosphorylation pathways of these two proteins in response to acute cocaine administration. A single cocaine administration (30 mg/kg) increased ERK-mediated signaling proteins, phosphoryation of cAMP response element-binding protein (CREB) kinase, pp90 ribosomal S6 kinase (RSK), and c-Fos protein levels in the caudate/putamen of Fischer rats. Acute cocaine administration also induced phosphorylation of the striatal-enriched protein tyrosine phosphatase (STEP) and decreased the phosphorylation of DARPP-32 protein at the Thr-75 site. The phosphorylation states of these inhibitors of ERK and DARPP-32 proteins may thus contribute to the effects of cocaine on ERK- and DARPP-32-mediated cascades, on gene expression and on behaviors.

Background: Sex differences in intracellular dopamine pathways may contribute to the known sex differences in psychomotor responses to cocaine and differential development of dependence. This study aimed to determine whether there are sex differences in the activation of the extracellular signal-regulated kinases (ERK1/2, or p44/p42 MAPK) and PKA phosphorylation-dependent substrates in the nucleus accumbens (NAcc) of male and female rats at baseline or after acute cocaine administration. Methods: 60-day-old male and female Fischer rats were injected with saline or cocaine (30 mg/kg) and sacrificed 5, 15, 30, 45 or 90 minutes later. Total locomotor activity, Stereotypic, rearing, and ambulatory behaviors was measured for 90 minutes using a two-frame automated Photobeam Activity Results: Similar to our previous findings, total locomotor activities were higher in female rats after this single cocaine administration. Females had higher levels of phosphorylated PKA substrates after cocaine administration, and this change lasted longer and had a greater magnitude than in cocaine treated male rats. Furthermore, although cocaine administration increased the phosphorylation of ERK proteins, there were no sex differences in p-ERK protein levels either at baseline or after acute cocaine administration. Conclusion: Taken together, these findings suggest that sex differences in basal and cocaine-induced alterations in PKA signaling activity in the NAcc may contribute to sex differences in psychomotor responses to cocaine. However, not all the components of the DA-intracellular signaling pathway maybe heightened in female rats as ERK phosphorylation patterns did not differ between the sexes.

This paper is aimed to assess the diagnostic value of MRI versus 99 Tcm-methylene diphosphonate (99 Tcm- MDP) bone scan (BS) for osseous metastases in patients with prostate cancer. The computer-based retrieval was conducted on PubMed, EMBASE, EBSCO, Web of Knowledge, the Cochrane Library and Ovid data bases to search for trials about diagnosing osseous metastases of prostate cancer with MRI and 99Tc"m-MDP BS. Selected with time acceptance and time exclusion criteria, the data quality were evaluated with QUADAS quality assessment tool and collected. We used the Meta-Disc software to conduct meta-analysis, and then calculated the pooled sensitivity, specificity and diagnostic odds ratio (DOR), drew the summary receiving operating characteristic (SROC) curve, and measured the area under curve (AUC) and Q value. Then five studies were included, involving 353 patients. The pooled sensitivity of MRI and BS was 0. 95 (95% CI 0. 90~0. 98) and 0. 67 (95% CI 0. 58~0. 75), respectively. The pooled specificity was 0. 97 (95% CI 0. 94~0. 99) and 0. 88 (95% CI 0. 83~0. 91), respectively. The pooled DOR was 402.99 (95% CI 119. 05 ~1364. 15) and 23. 85 (95% CI 1. 32~431. 48), respectively. The AUC was 0. 990 1 and 0. 624 1, respectively. The Q was 0. 958 7 and 0. 593 8. It can well be concluded that MRI is more effective than 99 Tcm-MDP BS in the diagnosis of osseous metastases in patients with prostate cancer.

Background: Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown. Methods: In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level. Results: Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner. Conclusions: These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions.

In the present study, the accuracy of the 4-dimensional model single photon emission computed tomography (4D-MSPECT) and quantitative gated single photon emission computed tomography (QGS) was investigated for assessing left ventricular end-diastolic (EDV), end-systolic volume (ESV) and ejection fraction (EF) from gated myocardial perfusion imaging (G-MPI) using left ventriculography (LVG) as reference. From December 2008 to June 2011, 85 patients, who underwent rest G-MPI and LVG (within 30 days) in West China Hospital, Sichuan University, were retrospectively recruited. EDV, ESV, and EF were calculated from G-MPI using 4D-MSPECT and QGS. Eighty-five patients (47 men, 38 women; age 57 +/- 13 years) were finally analyzed. Correlation between results of G-MPI and LVG was high for EDV, r = 0.89 (4D-MSPECT), r = 0.81 (QGS); ESV, r = 0.97 (4D-MSPECT), R = 0.95(QGS); EF, r = 0.95 (4D-MSPECT), r = 0.93 (QGS). 4D-MSPECT and QGS underestimated EDV significantly compared with LVG [(125 +/- 20) mL (4D-MSPECT), (118 +/- 39) mL (QGS), (131 +/- 33)mL (LVG)]. The ESV, 4D-MSPECT and QGS values did not differ significantly from LVG [(47 +/- 32) mL (4D-MSPECT), (53 +/- 29) mL (QGS), (49 +/- 37) mI (LVG)]. For LVEF, only QGS yielded values were significantly lower than LVG [61% +/- 21% (4D-MSPECT), 55% +/- 17% (QGS), and 63% +/- 19% (LVG)]. EDV, ESV, and EF as determined by 4D-MSPECT and QGS from G-MPI agree well with relevant values with LVG. However, Algorithm-inherent also showed slightly over- or under-estimation of volumes. Therefore, separated normal databases should be set up for each algorithm.

It is generally agreed that practice section is a mandatory part for effective medical imaging technologist education. In order to improve student performance in practice section in medical imaging technologist education, video clips and a computer simulation system were developed and applied. Student performance was evaluated and compared between two classes, one with the application of the video clips and computer simulation system, the other without. The students scored 4.5 points higher in the 4 three-hour practice sections because of the help of video clips and computer simulation. Statistical analysis using independent samples t-tests indicated that the difference was statistically significant. However, there was no significant difference between the scores in other aspects of student performance, including multiple-choice question sections and Q & A section in the term exam. It was concluded that in medical imaging technologist education, video clips and computer simulations that focus on practical procedures improved student performance in practice section.

Although readily available and convenient to use on PET/CT, SUV measurements are influenced by biologic and technologic factors like injected activity and scan duration. The aim of this study was to investigate the effect of varying scan duration on SUV using standard clinical activities of 18F-FDG. Patient PET/CT images were acquired in list-mode for 6 min in forty 18F-FDG oncology patients with known tumor. For each patient, data were sorted into 10 images of different durations (from 10 s to 6 min). SUVmax were measured for the lesions in the images. Tumor SUVmax were statistically analyzed taking the low-noise 6 min SUVmax as standard. For each of the nine scan duration from 10 s to 5 min, the normalized SUVmax were 1.080 ± 0.1611, 1.041 ± 0.1043, 1.005 ± 0.0732, 1.004 ± 0.0696, 1.005 ± 0.0456, 0.995 ± 0.0452, 0.996 ± 0.0299, 1.001 ± 0.0233, and 1.0002 ± 0.0144, respectively. One-sample t test revealed that the SUVmax biases for scan durations greater than 40 s were not statistically significant. It was concluded that scan duration as short as 40 s could be applied without compromising the quality of SUVmax measure.

Drug addiction is a chronic illness characterized by high rates of relapse. Relapse to drug use can be triggered by re-exposure to drug-associated cues, stressful events, or the drug itself after a period of abstinence. Pharmacological intervention to reduce the impact of relapse-instigating factors offers a promising target for addiction treatment. Growing evidence has implicated an important role of the orexin/hypocretin system in drug reward and drug-seeking, including animal models of relapse. Here, we review the evidence for the role of orexins in modulating reward and drug-seeking in animal models of addiction and the potential for orexin receptors as specific targets for anti-relapse medication approaches.

Previous studies have shown that female rats exhibit different patterns of drug seeking during multiple phases of cocaine addiction when compared with males. However, the underlying mechanisms for these sex differences remain largely unknown. Here, we used a cocaine self-administration/reinstatement model to examine neuronal activation, as determined by Fos expression, following cue-induced reinstatement of cocaine seeking in male and female rats. Fos expression revealed both similarities between sexes in some brain regions, as well as selective sexually dimorphic patterns. As compared to no cue control subjects, conditioned cues induced higher Fos expression in the Cg1 region of the anterior cingulate cortex, but lower expression in the nucleus accumbens in both males and females. Females exhibited higher Fos expression than males in multiple brain regions, including the agranular insular cortex, dorsal medial caudate-putamen, nucleus accumbens shell, ventral tegmental area, dorsal subiculum, and ventral CA1 and CA3 regions of the hippocampus. Notably, only Fos expression in the prelimbic cortex, nucleus accumbens shell, basolateral amygdala, and ventral subiculum correlated positively with lever responding in response to conditioned cues across males and females. These findings indicate that while sexually dimorphic Fos activation does occur, the relationship between cue-induced cocaine seeking and neuronal activation may be similar for males and females in key brain regions of the relapse circuit.

This paper is aimed to investigate the influence of gated myocardial perfusion imaging (G-MPI) with 8- and 16-frame acquisition models on the assessment of left ventricular function. Patients prepared for stress and rest G-MPI were prospectively recruited from January 2010 to January 2011 in the Department of Nuclear Medicine of West China Hospital, Sichuan University. Two separate G-MPI studies, one with 8 and the other with 16 frames, were simultaneously acquired during a single gantry orbit using Concurrent Imaging technique. We calculated the left ventricular ejection fraction (EF) and volumes using the Auto Quant software. Forty-eight patients (29 men, 19 women; average age 51 +/- 16 years old) were finally analyzed. The differences in left ventricular EF between 8- and 16-frame were small: 3.27% (95% CI: 6.41%-0.12%) for post-stress and 3.13% (95% CI: 5.93%-0.32%) for rest. Both using 8 and 16 frames, there were significantly larger volumes and lower EF in patients with stress-induced ischemia than without. As for detecting left ventricular EF, 8-frame and 16-frame acquisition models should not be mutually alternated.

Previous studies have shown that female rats exhibit enhanced cocaine seeking during multiple phases of cocaine addiction compared with males. The orexin/hypocretin system recently has been implicated in drug addiction in male rats. Based on the known sex differences in cocaine addiction, in the current study we examined orexin-mediated cocaine seeking during self-administration, extinction, and reinstatement in age-matched male (initial weight 250–300 g) and female (initial weight 175–225 g) Sprague-Dawley rats by using the orexin-1 receptor (OX1R) antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea (SB-334867) (10–30 mg/kg). OX1R blockade had no effect on established cocaine self-administration, but attenuated cocaine seeking during extinction in both male and female rats. It is noteworthy that OX1R blockade potently attenuated cue-induced reinstatement in males but had no effect on females. SB-334867 also reduced cocaine seeking during pharmacological stress-induced (yohimbine, 2.5 mg/kg) and yohimbine + cue-induced reinstatement in both sexes. SB-334867 failed to affect reinstatement induced by cocaine (10 mg/kg) in either male or female rats, but selectively reduced cocaine + cue-induced reinstatement only in males. In separate experiments examining basal and cocaine-induced locomotion, SB-334867 attenuated locomotion in both male and female rats. Finally, assessment of plasma and brain levels of SB-334867 showed that estrus females had slightly higher plasma levels than diestrus females, but no overall sex differences or estrous cycle differences were observed in plasma or brain SB-334867 concentrations. These results show that OX1R signaling plays a role in mediating cocaine seeking, but differs between the sexes for cue-induced reinstatement.

The aim of this study was to determine if progesterone affects spatial and non-spatial working memory in intact male and female rats.Rats received subcutaneous injections of progesterone (500 microg) or vehicle (sesame oil). Four hours after hormone treatments, spatial and non-spatial memories were tested using novel object recognition and spatial object recognition tasks.Vehicle-treated female rats had higher progesterone serum levels than males, but progesterone treatment produced equivalent progesterone serum levels in both sexes. In the object recognition task--a non-spatial memory task-females showed better performance than males, and progesterone had no effect on either sex. However, in the object replacement task--a spatial memory task-progesterone significantly impaired the retention in both male and female rats as compared with vehicle-treated groups.These results suggest that acute progesterone treatment interferes with spatial working memory consolidation, but not recognition (non-spatial) working memory. As such, the observed sexual incongruities in progesterone's effects on working memory suggest that progesterone-based hormone therapies have a negative impact on cognition.

Numerous studies have shown that biochemical and behavioral effects of cocaine are mediated by dopamine D1 receptor (D1R) and NMDA R1 receptor (NR1)-mediated transmissions. In this study, we investigated the physical interactions between D1R and NR1 in response to acute cocaine administration in a time course of 5 minutes to 60 minutes. In the caudate-putamen (CPu) of male Fischer rats, a single cocaine injection (30 mg/kg) reduced D1R-NR1 protein-protein interactions 30 minutes after treatment. In addition, activation or blockade of the NMDA receptor using NMDA (25 mg/kg) or MK-801 (0.25 mg/kg), respectively, also reduced the D1R-NR1 physical interactions. Acute cocaine administration did not alter total D1R or NR1 protein levels in our time course of study. These results indicate that D1R-NR1 physical interaction rather than total protein levels may regulate the intracellular signaling after acute cocaine administration.

An extensive body of literature provides evidence for both sexual dimorphism and menstrual cycle effects in drug abuse patterns and behavioral responses. However, the cellular mechanisms underlying sexually dimorphic responses to and hormonal effects on cocaine use remain unclear. We hypothesized that endogenous hormonal fluctuations during the estrous cycle of rats modulate cocaine's effects on dopamine- and PKA-mediated intracellular responses. To test this hypothesis, intact female rats at different stages of their cycle received a single injection of saline or cocaine (20 mg/kg) and were sacrificed after 15 or 60 min. The nucleus accumbens (NAc) and caudate putamen (CPu) were dissected and analyzed via Western blot for total and phosphorylated (p-thr34) dopamine- and 3'-5'-cyclic AMP-regulated phosphoprotein with molecular weight 32 kDa (DARPP-32), PP1, PP2B (CNA1 and CNB1 subunits), PKA, CREB, cFOS, and Delta-FosB. Our results show that saline-treated rats had estrous cycle-related differences in protein levels of pCREB, DARPP-32, p-thr34-DARPP-32, PP1, and CNA1. Saline-treated female rats in the estrus stage had higher levels of pCREB in the NAc, but cocaine-treatment lowered pCREB levels. The estrous cycle also significantly affected the magnitude of change for p-thr34-DARPP-32 protein levels in both the NAc and CPu. Sixty minutes of cocaine administration increased p-thr34-DARPP-32 levels in the NAc of rats during estrus and proestrus and in the CPu of rats in diestrus. Furthermore, cocaine-induced changes in PP1 protein levels in the NAc were also affected by the stage of the cycle; 60 min of cocaine administration increased PP1 levels in the NAc of rats during diestrus, whereas PP-1 levels decreased in rats during estrus. Taken together, these novel findings suggest that hormonal fluctuations during the estrous cycle may contribute to the previously reported sex differences in the PKA pathway and in behavioral responses to cocaine.

Behavioral and dopamine responses to cocaine are sexually dimorphic: Female rats exhibit higher levels of locomotor and reward-associated behaviors after cocaine administration and dopamine release than do males. Activation of the dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa (DARPP-32) intracellular cascade mediates responses to cocaine.To examine the possibility that acute cocaine administration alters the DARPP-32 cascade in a sexually dimorphic pattern.Male and female rats received either saline or cocaine (30 mg/kg). Protein levels of DARPP-32, phosphorylation of DARPP-32 at the Thr34 site (P-Thr34-DARPP-32), protein phosphatase 1 (PP-1), and protein phosphatase 2B (PP-2B) in nucleus accumbens were measured via Western blot analysis.Females had higher protein levels of DARPP-32, P-Thr34-DARPP-32, calcineurin A (CaN-A; catalytic subunit of PP-2B), and calcineurin B (CaN-B; regulatory subunit of PP-2B) than males 5 min after saline treatment. In females, CaN-A protein levels were also higher at 15 min and PP-1 protein levels were higher 30 min after saline administration than males. In male rats, cocaine significantly increased CaN-A protein levels at 30 min and CaN-B protein levels at 15 min. In females, cocaine administration significantly decreased protein levels of DARPP-32, P-Thr34-DARPP-32, and CaN-A at 45 min but increased PP-1 protein levels at 30 min. Overall, males had higher activation of the DARPP-32 pathway after cocaine administration than did females.These novel results show that basal and cocaine-induced sex differences in the DARPP-32/PP-1 cascade may be responsible for the sexual dimorphism in acute cocaine-induced behavioral responses.

Cocaine is an addictive psychostimulant that induces immediate early gene (IEG) expression by activating dopamine (DA) D1 and glutamate NMDA receptors in the striatum. In this study, we show that a single cocaine administration (30 mg/kg) time-dependently increases ERK phosphorylation, c-Fos and FosB protein expression, and MKP-1 phosphorylation (p-MKP-1), in the caudate-putamen (CPu) and nucleus accumbens (NAc) of Fischer rats. In the CPu, one hour after cocaine injection, the increase in c-Fos and FosB proteins expression is totally abolished by pre-administration of DA-D1 receptor antagonist, SCH23390. In the NAc, SCH23390 also inhibits cocaine-induced c-Fos protein expression. The pre-treatment of NMDA receptor antagonist, MK801, partially reduces cocaine-activated c-Fos protein expression in the CPu. Furthermore, the escalation of p-MKP-1 after acute cocaine administration is dependent on both DA-D1 and NMDA receptors activation in both brain regions examined. Our data suggest that cocaine may modulate ERK pathway signaling through the activation of DA-D1 and NMDA receptors, subsequently influencing the IEG protein expression.

To objectively and quantitatively study the effect of JPEG2000 lossy compression of nuclear medicine image, line source images of various noise levels, actual quadrant-bar phantom images and simulated quadrant-bar phantom images of various noise levels were compressed using a JPEG2000 plug-in at 10 : 1 to 50 : 1 with a 10 : 1 step. Modulation transfer function (MTF), full width at half-maximum (FWHM) and the peak to total count ratio (PTCR) of line spread function of the simulated line source images were analyzed quantitatively. Image quality of the quadrant-bar phantom images was visually evaluated according to quality control procedures and the result was used to verify the quantitative analysis. It was observed that PTCR decreased as compression ratio increased and the higher the noise level, the faster PTCR decreased, which was in accordance with the increase of the width of the smallest bars that can be visually resolved in the actual quadrant-bar phantom images and simulated quadrant-bar phantom images. On the other hand, no significant change of MTF and FWHM was observed as compression ratio increased. It was concluded that PTCR may serve as an objectively quantitative metrics of image quality assessment.

To study the usefulness of JPEG2000 compression for nuclear medicine (NM) image, normal and abnormal static images were compressed using a JPEG2000 plug-in. For lossless algorithm, the compressing ratio (CR) was calculated. For lossy algorithm, images were visually analyzed by NM physicians and ROC curves were generated. The area under ROC curve (AUC) was used as the index of image diagnostic quality. Paired sample t tests were performed to compare the AUCs. It was found that the lossless CR was (1.34+/-0.05) : 1. For lossy algorithm, the AUC decreased with the increase of CR. Comparison between the original and the compressed images revealed no significant difference for 10:1 CR but significant difference for bigger CRs. It was concluded that lossless compression has little usefulness for NM image because of very low CR. While lossy compression isused, the diagnostic quality of static NM images is preserved at CRs 50 : 1,40 : 1, 30 : 1,20 : 1 up to 10 : 1. For other types of NM image, CR should be increased or decreased according to their characteristics, especially the level of intrinsic statistical noise of NM image.