Testable two-loop radiative neutrino mass model based on an LLQdcQdcLLQd^cQd^c effective operator

A new two-loop radiative Majorana neutrino mass model is constructed from the gauge-invariant effective operator $L^i L^j Q^k d^c Q^l d^c \epsilon_{ik} \epsilon_{jl}$ that violates lepton number conservation by two units. The ultraviolet completion features two scalar leptoquark flavors and a color-octet Majorana fermion. We show that there exists a region of parameter space where the neutrino oscillation data can be fitted while simultaneously meeting flavor-violation and collider bounds. The model is testable through lepton flavor-violating processes such as ${\mu} \to e{\gamma}$, $\mu \to eee$, and $\mu N \to eN$ conversion, as well as collider searches for the scalar leptoquarks and color-octet fermion. We computed and compiled a list of necessary Passarino-Veltman integrals up to boxes in the approximation of vanishing external momenta and made them available as a Mathematica package, denoted as ANT.Comment: 42 pages, 11 figures, typo in Eq. (4.9) as well as wrong chirality structures in Secs. 4.5 and 5.2 corrected, final results unchange

WHEN A FIRE LEADS TO A DRINK: ENHANCEMENT OF ALCOHOL-SEEKING BY MICROINJECTIONS OF NICOTINE DIRECTLY INTO THE REWARD NEUROCIRCUITRY

poster abstractAlcohol addiction is a cyclical disorder that is characterized by periods of alcohol consumption and abstinence. The periods of abstinence are frequently brief, and the rate of relapse to alcohol consumption is typically higher than 95% within a year. Most alcoholics are not just alcoholics. The vast majority (80-95%) of alcoholics also concurrently use, or are dependent on, nicotine. During periods of alcohol abstinence, nicotine use dramatically increases. The use of nicotine can potentiate self-reported craving for alcohol and the amount of alcohol used following a relapse episode. The goal of the present project was to determine the biological basis of nicotine’s ability to stimulate alcohol (EtOH)-seeking in a rodent model of alcoholism (alcohol-preferring [P] rat). Specifically, the current project examined the effect of nicotine on EtOH-seeking when administered directly into the brain reward neurocircuit (posterior Ventral Tegmental Area – pVTA). In order to determine the neurotransmitter systems regulating nicotine’s ability to enhance EtOH-seeking when administered into the pVTA, two subsequent studies examined the effect of co-administration of nicotine with a acetylcholine nicotine receptor (AchN) antagonist (mecamylamine (MEC)) or with a serotonin-3 (5HT3) receptor antagonist (zacopride (Zac)). Nicotine binds with high affinity to both the AchN and 5HT3 receptors. The data collected indicated that at very low concentrations nicotine microinjected into the pVTA increased EtOH-seeking in P rats. Co-administration of mecamylamine or zacopride blocked nicotine’s ability to potentiate EtOH-seeking. Overall, the results show that nicotine can enhance alcohol-seeking behaviors through activation of the AchN and 5-HT3 receptors in pVTA. The clinical implication of the data set would be that to reduce the amount of alcohol-craving, which could lead to relapse, nicotine use should also be terminated

Ethanol increases glutamate neurotransmission in the posterior ventral tegmental area of female Wistar rats

Background— The posterior ventral tegmental area (pVTA) mediates the reinforcing and stimulating effects of ethanol (EtOH). Electrophysiological studies indicated that exposure to EtOH increased glutamate synaptic function in the VTA. The current study determined the neurochemical effects of both acute and repeated EtOH exposure on glutamate neurotransmission in the pVTA. Methods— Adult female Wistar rats were implanted with microdialysis probes in the pVTA. During microdialysis, rats received acute i.p. injection of saline or EtOH (0.5, 1.0 or 2.0 g/kg) and extracellular glutamate levels were measured in the pVTA. The effects of repeated daily injections of EtOH (0.5, 1.0, or 2.0 g/kg) on basal extracellular glutamate concentrations in the pVTA and on glutamate response to a subsequent EtOH challenge were also examined. Results— The injection of 0.5 g/kg EtOH significantly increased (120–125 % of baseline), whereas injection of 2.0 g/kg EtOH significantly decreased (80% of baseline) extracellular glutamate levels in the pVTA. The dose of 1.0 g/kg EtOH did not alter extracellular glutamate levels. Seven repeated daily injections of each dose of EtOH increased basal extracellular glutamate concentrations (from 4.1 ± 0.5 to 9.2 ± 0.5 μM) and reduced glutamate clearance in the pVTA (from 30 ± 2% to 17 ± 2%), but failed to alter glutamate response to a 2.0 g/kg EtOH challenge. Conclusion— The results suggest that the low dose of EtOH can stimulate the release of glutamate in the pVTA, and repeated EtOH administration increased basal glutamate transmission in the pVTA, as a result of reduced glutamate clearance

Molar incisor hypomineralisation: current knowledge and practice

Background Molar incisor hypomineralisation (MIH) is a common developmental dental condition that presents in childhood. Areas of poorly formed enamel affect one or more first permanent molars and can cause opacities on the anterior teeth. MIH presents a variety of challenges for the dental team as well as functional and social impacts for affected children. Objectives Here, we provide an up‐to‐date review of the epidemiology, aetiology, diagnosis and clinical management of MIH. Materials and methods A review of the contemporary basic science and clinical literature, relating to MIH, was undertaken using information obtained (up to 10 April 2020) from the electronic databases PubMed, Scopus, Web of Science and the Cochrane Library. Results There is a growing body of evidence relating to the aetiology, presentation and clinical management of MIH. Current knowledge appears to be focused on potential genetic aspects, as well as the development and validation of indices for the diagnosis and management of MIH. There has also been increasing recognition of the global and individual burden of this common condition. Conclusions Dental health professionals should regularly appraise the basic science and clinical MIH literature to ensure that they provide the best possible short‐ and long‐term care for their young patients

How safe is sex with condoms? An in-depth investigation of the condom use pattern during the last sex act in an urban area of Bangladesh

The policy of condom intervention is based on achieving ejaculation inside a condom, a "mechanical" goal of sexual interaction. However, most research on condom use has focused upon a simplistic reliance on survey results of condom use during the last sex act. Interviews with 20 hotel-based female sex workers and 15 (male) clients were conducted to explore patterns of claimed condom use during the last sex act. The Health Belief Model guided this study and was found deficient in providing an understanding of condom use. The clients' (male) perceptions of sexuality and "the male's right" to engage in sexual intercourse in commercial settings increased condom use. The invisibility of AIDS reduced participants' perceived susceptibility to and severity of suffering from the disease, while using condoms at any time during intercourse was perceived as being beneficial. Condom interventions need to be based on deeper understanding of the complexity of people's lives

The reinforcing effects of ethanol within the posterior ventral tegmental area depend on dopamine neurotransmission to forebrain cortico-limbic systems

Ethanol can be self-infused directly into the posterior ventral tegmental area (pVTA) and these effects involve activation of local dopamine neurons. However, the neuro-circuitry beyond the pVTA involved in these reinforcing effects has not been explored. Intra-pVTA microinjection of ethanol increases dopamine release in the nucleus accumbens (NAC), medial prefrontal cortex (mPFC) and ventral pallidum (VP). The present study tested the hypothesis that the reinforcing effects of ethanol within the pVTA involve the activation of dopamine projections from the pVTA to the NAC, VP and mPFC. Following the acquisition of self-infusions of 200 mg% ethanol into the pVTA, either the dopamine D2 receptor antagonist sulpiride (0, 10 or 100 μM) or the D1 receptor antagonist SCH-23390 (0, 10 or 100 μM) was microinjected into the ipsilateral NAC shell (NACsh), NAC core (NACcr), VP or mPFC immediately prior to the self-infusion sessions to assess the involvement of the different dopamine projections in the reinforcing effects of ethanol. Microinjection of each compound at higher concentration into the NACsh, VP or mPFC, but not the NACcr, significantly reduced the responses on the active lever (from 40-50 to approximately 20 responses). These results indicate that activation of dopamine receptors in the NACsh, VP or mPFC, but not the NACcr, is involved in mediating the reinforcing effects of ethanol in the pVTA, suggesting that the 'alcohol reward' neuro-circuitry consist of, at least in part, activation of the dopamine projections from the pVTA to the NACsh, VP and mPFC

Microinjections of acetaldehyde or salsolinol into the posterior ventral tegmental area increase dopamine release in the nucleus accumbens shell

BACKGROUND: Published findings indicate that acetaldehyde (ACD; the first metabolite of ethanol [EtOH]) and salsolinol (SAL; formed through the nonenzymatic condensation of ACD and dopamine [DA]) can be formed following EtOH consumption. Both ACD and SAL exhibit reinforcing properties within the posterior ventral tegmental area (pVTA) and both exhibit an inverted "U-shaped" dose-response curve. The current study was undertaken to examine the dose-response effects of microinjections of ACD or SAL into the pVTA on DA efflux in the nucleus accumbens shell (AcbSh). METHODS: For the first experiment, separate groups of male Wistar rats received pulse microinjections of artificial cerebrospinal fluid (aCSF) or 12-, 23-, or 90-μM ACD into the pVTA, while extracellular DA levels were concurrently measured in the AcbSh. The second experiment was similarly conducted, except rats were given microinjections of aCSF or 0.03-, 0.3-, 1.0-, or 3.0-μM SAL, while extracellular levels of DA were measured in the AcbSh. RESULTS: Both ACD and SAL produced a dose-dependent inverted "U-shaped" response on DA release in the AcbSh, with 23-μM ACD (200% baseline) and 0.3-μM SAL (300% baseline) producing maximal peak responses with higher concentrations of ACD (90 μM) and SAL (3.0 μM) producing significantly lower DA efflux. CONCLUSIONS: The findings from the current study indicate that local application of intermediate concentrations of ACD and SAL stimulated DA neurons in the pVTA, whereas higher concentrations may be having secondary effects within the pVTA that inhibit DA neuronal activity. The present results parallel the studies on the reinforcing effects of ACD and SAL in the pVTA and support the idea that the reinforcing effects of ACD and SAL within the pVTA are mediated by activating DA neurons

Sequencing and characterization of the guppy (Poecilia reticulata) transcriptome

Background: Next-generation sequencing is providing researchers with a relatively fast and affordable option for developing genomic resources for organisms that are not among the traditional genetic models. Here we present a de novo assembly of the guppy (Poecilia reticulata) transcriptome using 454 sequence reads, and we evaluate potential uses of this transcriptome, including detection of sex-specific transcripts and deployment as a reference for gene expression analysis in guppies and a related species. Guppies have been model organisms in ecology, evolutionary biology, and animal behaviour for over 100 years. An annotated transcriptome and other genomic tools will facilitate understanding the genetic and molecular bases of adaptation and variation in a vertebrate species with a uniquely well known natural history. Results: We generated approximately 336 Mbp of mRNA sequence data from male brain, male body, female brain, and female body. The resulting 1,162,670 reads assembled into 54,921 contigs, creating a reference transcriptome for the guppy with an average read depth of 28×. We annotated nearly 40% of this reference transcriptome by searching protein and gene ontology databases. Using this annotated transcriptome database, we identified candidate genes of interest to the guppy research community, putative single nucleotide polymorphisms (SNPs), and male-specific expressed genes. We also showed that our reference transcriptome can be used for RNA- sequencing-based analysis of differential gene expression. We identified transcripts that, in juveniles, are regulated differently in the presence and absence of an important predator, Rivulus hartii, including two genes implicated in stress response. For each sample in the RNA-seq study, >50% of high-quality reads mapped to unique sequences in the reference database with high confidence. In addition, we evaluated the use of the guppy reference transcriptome for gene expression analyses in a congeneric species, the sailfin molly (Poecilia latipinna). Over 40% of reads from the sailfin molly sample aligned to the guppy transcriptome. Conclusions: We show that next-generation sequencing provided a reliable and broad reference transcriptome. This resource allowed us to identify candidate gene variants, SNPs in coding regions, and sex-specific gene expression, and permitted quantitative analysis of differential gene expression

The reinforcing effects of ethanol within the nucleus accumbens shell involve activation of local GABA and serotonin receptors

Ethanol is reinforcing within the nucleus accumbens shell (NACsh), but the underlying mechanisms remain unclear. Ethanol can potentiate the function of the GABAA, GABAB, and serotonin-3 (5-HT3) receptors. Therefore, the current study tested the hypothesis that activation of these receptors would be involved in the reinforcing effects of ethanol in the NACsh. An intracranial self-administration (ICSA) procedure was used to assess the reinforcing effects of ethanol in the NACsh of alcohol preferring (P) rats. The ICSA consisted of seven sessions: four sessions to establish 150 mg% ethanol self-infusion into the NACsh; sessions 5 and 6 with co-infusion of ethanol plus one concentration of the GABAA antagonist bicuculline (10 or 100 µM), the GABAB antagonist SCH 50911 (50, 75 or 100 µM), or the 5-HT3 receptor antagonist zacopride (10 or 100 µM); and session 7 with 150 mg% ethanol alone. All groups self-infused ethanol into the NACsh and readily discriminated the active from inactive lever during the acquisition sessions. Co-infusion of 100 µM, but not 10 µM, bicuculline or zacopride significantly decreased active responses during sessions 5 and 6. Co-infusion of 75 µM, but not 50 or 100 µM, SCH 50911 significantly attenuated responses for ethanol. Overall, the results suggest that the reinforcing effects of ethanol in the NACsh may be modulated by activation of local GABAA, GABAB and 5-HT3 receptors

Cocaine influences alcohol-seeking behavior and relapse drinking in alcohol-preferring (P) rats

BACKGROUND: The results of several studies suggest that there may be common neurocircuits regulating drug-seeking behaviors. Common biological pathways regulating drug-seeking would explain the phenomenon that seeking for 1 drug can be enhanced by exposure to another drug of abuse. The objective of this study was to assess the time course effects of acute cocaine administration on ethanol (EtOH) seeking and relapse. METHODS: Alcohol-preferring (P) rats were allowed to self-administer 15% EtOH and water. EtOH-seeking was assessed through the use of the Pavlovian spontaneous recovery (PSR) model, while EtOH-relapse drinking was assessed through the use of the alcohol-deprivation effect. RESULTS: Cocaine (0, 1, or 10 mg/kg), injected immediately, 30 minutes, or 4 hours prior to the first PSR testing session, dose-dependently increased responding on the EtOH lever compared to extinction responses and responding by saline controls. Under relapse conditions, cocaine given immediately prior to the relapse session had no effect (1 mg/kg) or reduced responding (10 mg/kg). In contrast, cocaine given 4 hours prior to the relapse session markedly enhanced EtOH responding compared to saline. CONCLUSIONS: The enhanced expression of EtOH-seeking and EtOH-relapse behaviors may be a result of a priming effect of cocaine on neuronal circuits mediating these behaviors. The effect of cocaine on EtOH-relapse drinking is indicative of the complex interactions that can occur between drugs of abuse; production of conflicting behaviors (immediate), and priming of relapse/seeking (4-hour delay)