Mood selectively moderates the implicit alcohol association-drinking relation in college student heavy episodic drinkers

Multiple studies indicate that implicit alcohol-related associations (i.e., indices of relatively fast, spontaneous processes) predict drinking. An important next step is to investigate moderators of the implicit association-drinking relationship. Mood state has been proposed as a moderator of this relationship: implicit associations have been theorized to be stronger predictors of drinking under positive mood states. From the same theoretical perspective, explicit measures (indices of relatively slow, reflective processes) have been proposed to be stronger predictors of drinking under negative mood states. The current study evaluated these hypotheses by investigating whether mood state (manipulated via exposure to a brief video clip) moderated the relations between three types of implicit alcohol-related associations (alcohol excite, alcohol approach, and drinking identity), their explicit counterparts, and drinking in a taste test that included beer and soft drinks. A sample of 152 undergraduate social drinkers (81 men; 71 women) completed baseline measures of implicit alcohol-related associations, their explicit counterparts, and typical drinking behaviors. Participants then viewed a mood-state-inducing video clip (positive, neutral, or negative), and completed the taste test. Results were mixed but generally indicated that prediction of drinking by baseline implicit alcohol excite (but not alcohol approach or drinking identity) associations was moderated by mood. Specifically, implicit alcohol excite associations were more negatively associated with drinking after viewing the sad video and more positively associated with drinking after watching the happy/neutral video. Moderation was also observed for the explicit counterpart of alcohol excite. Findings are discussed in terms of models of negative reinforcement drinking

Neuromuscular synaptic function in mice lacking major subsets of gangliosides

Gangliosides are a family of sialylated glycosphingolipids enriched in the outer leaflet of neuronal membranes, in particular at synapses. Therefore, they have been hypothesized to play a functional role in synaptic transmission. We have measured in detail the electrophysiological parameters of synaptic transmission at the neuromuscular junction (NMJ) ex vivo of a GD3-synthase knockout mouse, expressing only the O- and a-series gangliosides, as well as of a GM2/GD2-synthase*GD3-synthase double-knockout (dKO) mouse, lacking all gangliosides except GM3. No major synaptic deficits were found in either null-mutant. However, some extra degree of rundown of acetylcholine release at high intensity use was present at the dKO NMJ and a temperature-specific increase in acetylcholine release at 35 °C was observed in GD3-synthase knockout NMJs, compared with wild-type. These results indicate that synaptic transmission at the NMJ is not crucially dependent on the particular presence of most ganglioside family members and remains largely intact in the sole presence of GM3 ganglioside. Rather, presynaptic gangliosides appear to play a modulating role in temperature- and use-dependent fine-tuning of transmitter output

Association between an insulin-like growth factor I gene promoter polymorphism and bone mineral density in the elderly: the Rotterdam Study

Studies of the roles of variants of the IGF-I gene in the regulation of bone mineral density (BMD) have yielded conflicting results. We examined the role of a microsatellite repeat polymorphism in one of the promoter regions of the IGF-I gene in relation to femoral BMD in elderly women and men from the Rotterdam Study. We studied 5648 and 4134 individuals at baseline and follow-up ( approximately 2 yr later), respectively. Femoral BMD measurements were performed using dual energy x-ray absorptiometry. In women, baseline BMD levels were, on the average, 0.02 g/cm(2) [95% confidence interval (CI) for difference, -0.03, -0.00 g/cm(2)] lower in individuals without the 192-bp allele as compared with the homozygotes for the allele (P = 0.03). The mean rate of BMD change from baseline to follow-up was -6.9 mg/cm(2) (95% CI, -10.8, -3.0), -4.5 mg/cm(2) (95% CI, -6.4, -2.5), and -2.3 mg/cm(2) (95% CI, -4.2, 0.3) in noncarriers, heterozygotes, and homozygotes for the 192-bp allele, respectively (P trend = 0.03). Adjustment for age and body mass index did not essentially change this relation. No such effects were observed in men. Our findings suggest that this promoter polymorphism or another functional polymorphism in linkage disequilibrium may be a genetic determinant of BMD levels and rate of bone loss in postmenopausal women

Specific heat study of single crystalline Pr0.63_{0.63} Ca0.37_{0.37} MnO3_{3} in presence of a magnetic field

We present the results of a study of specific heat on a single crystal of Pr$_{0.63}$Ca$_{0.37}$MnO$_3$ performed over a temperature range 3K-300K in presence of 0 and 8T magnetic fields. An estimate of the entropy and latent heat in a magnetic field at the first order charge ordering (CO) transition is presented. The total entropy change at the CO transition which is $\approx$ 1.8 J/mol K at 0T, decreases to $\sim$ 1.5 J/mol K in presence of 8T magnetic field. Our measurements enable us to estimate the latent heat $L_{CO}$ $\approx$ 235 J/mol involved in the CO transition. Since the entropy of the ferromagnetic metallic (FMM) state is comparable to that of the charge-ordered insulating (COI) state, a subtle change in entropy stabilises either of these two states. Our low temperature specific heat measurements reveal that the linear term is absent in 0T and surprisingly not seen even in the metallic FMM state.Comment: 8 pages (in RevTEX format), 12 figures (in postscript format) Submitted to Phys. Rev.

Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity

The study of rare families with inherited pain insensitivity can identify new human-validated analgesic drug targets. Here, a 66-yr-old female presented with nil requirement for postoperative analgesia after a normally painful orthopaedic hand surgery (trapeziectomy). Further investigations revealed a lifelong history of painless injuries, such as frequent cuts and burns, which were observed to heal quickly. We report the causative mutations for this new pain insensitivity disorder: the co-inheritance of (i) a microdeletion in dorsal root ganglia and brain-expressed pseudogene, FAAH-OUT, which we cloned from the fatty-acid amide hydrolase (FAAH) chromosomal region; and (ii) a common functional single-nucleotide polymorphism in FAAH conferring reduced expression and activity. Circulating concentrations of anandamide and related fatty-acid amides (palmitoylethanolamide and oleoylethanolamine) that are all normally degraded by FAAH were significantly elevated in peripheral blood compared with normal control carriers of the hypomorphic single-nucleotide polymorphism. The genetic findings and elevated circulating fatty-acid amides are consistent with a phenotype resulting from enhanced endocannabinoid signalling and a loss of function of FAAH. Our results highlight previously unknown complexity at the FAAH genomic locus involving the expression of FAAH-OUT, a novel pseudogene and long non-coding RNA. These data suggest new routes to develop FAAH-based analgesia by targeting of FAAH-OUT, which could significantly improve the treatment of postoperative pain and potentially chronic pain and anxiety disorders. - 2019 The Author(s)Medical Research Council (Career Development Award G1100340 to JJC); Wellcome Trust ( 200183/Z/15/Z to JJC, 095698Z/11/Z and 202747/Z/16/Z to DLHB); Alzheimer's Society (research fellowship to JTB), University of Cambridge Academic Foundation Programme (to MCL); Molecular Nociception Group (to MCL); National Institutes of Health (Bethesda, MD, USA) Ruth L. Kirschstein Institutional National Research Service Award (to MCL); Wellcome Trust funded London Pain Consortium (to JDR); Colciencias through a Francisco Jose de Caldas Scholarship (LASPAU, Harvard University) (to JDR); Canadian Institutes of Health Research (CIHR; to MNH); CIHR (postdoctoral funding to MM)

Methods for interpreting lists of affected genes obstained in a DNA microarray experiment

Background - The aim of this paper was to describe and compare the methods used and the results obtained by the participants in a joint EADGENE (European Animal Disease Genomic Network of Excellence) and SABRE (Cutting Edge Genomics for Sustainable Animal Breeding) workshop focusing on post analysis of microarray data. The participating groups were provided with identical lists of microarray probes, including test statistics for three different contrasts, and the normalised log-ratios for each array, to be used as the starting point for interpreting the affected probes. The data originated from a microarray experiment conducted to study the host reactions in broilers occurring shortly after a secondary challenge with either a homologous or heterologous species of Eimeria. Results - Several conceptually different analytical approaches, using both commercial and public available software, were applied by the participating groups. The following tools were used: Ingenuity Pathway Analysis, MAPPFinder, LIMMA, GOstats, GOEAST, GOTM, Globaltest, TopGO, ArrayUnlock, Pathway Studio, GIST and AnnotationDbi. The main focus of the approaches was to utilise the relation between probes/genes and their gene ontology and pathways to interpret the affected probes/genes. The lack of a well-annotated chicken genome did though limit the possibilities to fully explore the tools. The main results from these analyses showed that the biological interpretation is highly dependent on the statistical method used but that some common biological conclusions could be reached. Conclusion - It is highly recommended to test different analytical methods on the same data set and compare the results to obtain a reliable biological interpretation of the affected genes in a DNA microarray experimen

On the magnetism of Ln{2/3}Cu{3}Ti{4}O{12} (Ln = lanthanide)

The magnetic and thermodynamic properties of the complete Ln$_{2/3}$Cu$_3$Ti$_4$O$_{12}$ series were investigated. Here $Ln$ stands for the lanthanides La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb. %Most of the compounds were prepared as single phase polycrystalline powder %without any traces of impurities. Marginal amounts of %impurities $(< 2$ were detected $Ln=$ Gd, Er, and Tm. %Significant amounts of impurity phases were found for $Ln=$ Ce and Yb. All the samples investigated crystallize in the space group $Im\bar{3}$ with lattice constants that follow the lanthanide contraction. The lattice constant of the Ce compound reveals the presence of Ce$^{4+}$ leading to the composition Ce$_{1/2}$Cu$_3$Ti$_4$O$_{12}$. From magnetic susceptibility and electron-spin resonance experiments it can be concluded that the copper ions always carry a spin $S=1/2$ and order antiferromagnetically close to 25\,K. The Curie-Weiss temperatures can approximately be calculated assuming a two-sublattice model corresponding to the copper and lanthanide ions, respectively. It seems that the magnetic moments of the heavy rare earths are weakly coupled to the copper spins, while for the light lanthanides no such coupling was found. The $4f$ moments remain paramagnetic down to the lowest temperatures, with the exception of the Tm compound, which indicates enhanced Van-Vleck magnetism due to a non-magnetic singlet ground state of the crystal-field split $4f$ manifold. From specific-heat measurements we accurately determined the antiferromagnetic ordering temperature and obtained information on the crystal-field states of the rare-earth ions. The heat-capacity results also revealed the presence of a small fraction of Ce$^{3+}$ in a magnetic $4f^1$ state.Comment: 10 pages, 10 figure

Insulin-like growth factor I gene promoter polymorphism, collagen type II alpha1 (COL2A1) gene, and the prevalence of radiographic osteoarthritis: the Rotterdam Study

OBJECTIVE: To examine the role of an IGF-I gene promoter polymorphism in the prevalence of radiographic osteoarthritis (ROA), and study its interaction with the COL2A1 gene. METHODS: Individuals genotyped for IGF-I (n = 1546) and COL2A1 gene polymorphisms (n = 808) were selected from a random sample (n = 1583) derived from the Rotterdam study. The presence of ROA was defined as a Kellgren score of 2 or more in at least one of four joints (knee, hip, hand, and spine). Genotype specific odds ratios (OR) were adjusted for age, sex, body mass index, and bone mineral density using logistic regression. Interaction with the COL2A1 genotype was tested. RESULTS: Overall, no association was found between the IGF-I polymorphism and ROA. In subjects aged 65 years or younger (n = 971), the prevalence of ROA increased with the absence of the 192 base pair (bp) allele (p for trend = 0.03). Compared with homozygotes for the 192 bp allele, the prevalence of ROA was 1.4 times higher in heterozygotes (95% confidence interval, 1.0 to 1.8) and 1.9 times higher in non-carriers (1.1 to 3.3). There was evidence of interaction between the IGF-I and COL2A1 genes. Individuals with the risk genotype of both genes had an increased prevalence of ROA (OR 3.4 (1.1 to 10.7)). No effect was observed in subjects older than 65 years. CONCLUSIONS: SUBJECTS: with genetically determined low IGF-I expression (non-carriers of the 192 bp allele) may be at increased risk of ROA before the age of 65 years. Furthermore, an interaction between the IGF-I and COL2A1 genes is suggested

Colossal dielectric constants in transition-metal oxides

Many transition-metal oxides show very large ("colossal") magnitudes of the dielectric constant and thus have immense potential for applications in modern microelectronics and for the development of new capacitance-based energy-storage devices. In the present work, we thoroughly discuss the mechanisms that can lead to colossal values of the dielectric constant, especially emphasising effects generated by external and internal interfaces, including electronic phase separation. In addition, we provide a detailed overview and discussion of the dielectric properties of CaCu3Ti4O12 and related systems, which is today's most investigated material with colossal dielectric constant. Also a variety of further transition-metal oxides with large dielectric constants are treated in detail, among them the system La2-xSrxNiO4 where electronic phase separation may play a role in the generation of a colossal dielectric constant.Comment: 31 pages, 18 figures, submitted to Eur. Phys. J. for publication in the Special Topics volume "Cooperative Phenomena in Solids: Metal-Insulator Transitions and Ordering of Microscopic Degrees of Freedom