First determination of the CPCP content of D→π+π−π+π−D \to \pi^+\pi^-\pi^+\pi^- and updated determination of the CPCP contents of D→π+π−π0D \to \pi^+\pi^-\pi^0 and D→K+K−π0D \to K^+K^-\pi^0

Quantum-correlated $\psi(3770) \to D\bar{D}$ decays collected by the CLEO-c experiment are used to perform a first measurement of $F_+^{4\pi}$, the fractional $CP$-even content of the self-conjugate decay $D \to \pi^+\pi^-\pi^+\pi^-$, obtaining a value of $0.737 \pm 0.028$. An important input to the measurement comes from the use of $D \to K^0_{\rm S}\pi^+\pi^-$ and $D \to K^0_{\rm L}\pi^+\pi^-$ decays to tag the signal mode. This same technique is applied to the channels $D \to\pi^+\pi^-\pi^0$ and $D \to K^+K^-\pi^0$, yielding $F_+^{\pi\pi\pi^0} = 1.014 \pm 0.045 \pm 0.022$ and $F_+^{KK\pi^0} = 0.734 \pm 0.106 \pm 0.054$, where the first uncertainty is statistical and the second systematic. These measurements are consistent with those of an earlier analysis, based on $CP$-eigenstate tags, and can be combined to give values of $F_+^{\pi\pi\pi^0} = 0.973 \pm 0.017$ and $F_+^{KK\pi^0} = 0.732 \pm 0.055$. The results will enable the three modes to be included in a model-independent manner in measurements of the unitarity triangle angle $\gamma$ using $B^\mp \to DK^\mp$ decays, and in time-dependent studies of $CP$ violation and mixing in the $D\bar{D}$ system.Comment: Minor revisions following journal acceptanc

Individual differences in visual and olfactory cue preference and use by cats (Felis catus)

Highlights • Eight cats were trained in a T-maze using a two-alternative forced choice procedure. • Cats could use either an olfactory or visual cue to locate a food reward. • Cues were then put in conflict to determine which was preferred for the task. • Most cats used the visual cue to learn the location of the food. • Preferences were stable, repeatable and rapidly learned. -------------------------------------------------------------------------------- Abstract Animals are constantly presented with stimuli through different sensory challenges, which may sometimes contain contradictory information and so they must decide which is more salient in a given situation. Both vision and olfaction are extensively utilised by the domestic cat (Felis catus) in a variety of biological contexts, but which modality tends to take priority when the two channels contain information of similar potential value is unknown, as is the tendency for different individuals to use different cues in relation to the same situation. Such individual difference may have important clinical implications as it may help to explain why animals living within the same house may respond differently to the same environment. For example a change in the olfactory features of the environment may be stressful to an individual who has a bias towards using this sensory modality, but have no significant impact on individuals who rely more on visual cues for orientation. Eight cats were trained in a T-maze using a two-alternative forced choice procedure. The positive and negative stimuli presented both visual and olfactory information. Thus, there were two cues that the cats could use in order to make the discrimination. After reaching criterion for their training stimuli the six successful cats were presented with a feature mismatch test in which the positive visual stimuli were combined with the negative olfactory stimuli and vice versa. This investigated which cues were of greater salience to them. Four out of six cats showed a significant preference (P = 0.022- 0.006) for the visual cue, but one individual showed a consistent preference for using the olfactory cue (P = 0.019). To investigate whether the cats using visual cues had learned anything about the olfactory stimulus, four were given an additional test in which they were presented with the olfactory stimulus alone. Three out of four cats successfully made this discrimination, (P = 0.006-0.003, unsuccessful cat P = 0.076). This demonstrated that the cats had the potential to use olfactory cues in the absence of visual ones. These results highlight the importance of considering sensory preferences as an individual trait, which may vary substantially from population level effects

CACNA1C: Association with pychiatric disorders, behavior, and neurogenesis

Large-scale genome-wide association studies have consistently shown that genetic variation in CACNA1C, a gene that encodes calcium voltage-gated channel subunit alpha1C, increases risk for psychiatric disorders. CACNA1C encodes the Cav1.2 subunit of voltage-gated calcium channels, which themselves have been functionally implicated in a broad spectrum of neuropsychiatric syndromes. Research has concentrated on uncovering the underlying biological mechanisms that could be responsible for this increased risk. This review presents an overview of recent findings regarding Cacna1c variation in animal models, particularly focusing on behavioral phenotypes associated with neurodevelopmental disorders such as cognition, anxiety and depressive phenotypes, and fear conditioning. The impact of reduced gene dosage of Cacna1c on adult hippocampal neurogenesis is also assessed, including new data from a novel Cacna1c+/− rat model

FMRP and CYFIP1 at the synapse and their role in psychiatric vulnerability

There is increasing awareness of the role genetic risk variants have in mediating vulnerability to psychiatric disorders such as schizophrenia and autism. Many of these risk variants encode synaptic proteins, influencing biological pathways of the postsynaptic density and, ultimately, synaptic plasticity. Fragile X Mental Retardation 1 (FMR1) and Cytoplasmic FRMP-Interacting Protein (CYFIP1) contain two such examples of highly penetrant risk variants and encode synaptic proteins with shared functional significance. In this Review, we will discuss the biological actions of FMRP and CYFIP1, including their regulation of i) protein translation and specifically FMRP targets, ii) dendritic and spine morphology and iii) forms of synaptic plasticity such as long-term depression. We draw upon a range of preclinical studies that have used genetic dosage models of FMR1 and CYFIP1 to determine their biological function. In parallel, we discuss how clinical studies of Fragile X Syndrome or 15q11.2 deletion patients have informed our understanding of FMRP and CYFIP1 proteins, and highlight the latest psychiatric genomic findings that continue to implicate FMRP and CYFIP1. Lastly, we assess the current limitations in our understanding of FMRP and CYFIP1 biology and how they must be addressed before mechanism-led therapeutic strategies can be developed for psychiatric disorders

The regulation of cytokine networks in hippocampal CA1 differentiates extinction from those required for the maintenance of contextual fear memory after recall

We investigated the distinctiveness of gene regulatory networks in CA1 associated with the extinction of contextual fear memory (CFM) after recall using Affymetrix GeneChip Rat Genome 230 2.0 Arrays. These data were compared to previously published retrieval and reconsolidation-attributed, and consolidation datasets. A stringent dual normalization and pareto-scaled orthogonal partial least-square discriminant multivariate analysis together with a jack-knifing-based cross-validation approach was used on all datasets to reduce false positives. Consolidation, retrieval and extinction were correlated with distinct patterns of gene expression 2 hours later. Extinction-related gene expression was most distinct from the profile accompanying consolidation. A highly specific feature was the discrete regulation of neuroimmunological gene expression associated with retrieval and extinction. Immunity–associated genes of the tyrosine kinase receptor TGFβ and PDGF, and TNF families’ characterized extinction. Cytokines and proinflammatory interleukins of the IL-1 and IL-6 families were enriched with the no-extinction retrieval condition. We used comparative genomics to predict transcription factor binding sites in proximal promoter regions of the retrieval-regulated genes. Retrieval that does not lead to extinction was associated with NF-κB-mediated gene expression. We confirmed differential NF-κBp65 expression, and activity in all of a representative sample of our candidate genes in the no-extinction condition. The differential regulation of cytokine networks after the acquisition and retrieval of CFM identifies the important contribution that neuroimmune signalling plays in normal hippocampal function. Further, targeting cytokine signalling upon retrieval offers a therapeutic strategy to promote extinction mechanisms in human disorders characterised by dysregulation of associative memory

Beta-decay properties of 25^{25}Si and 26^{26}P

The $\beta$-decay properties of the neutron-deficient nuclei $^{25}$Si and $^{26}$P have been investigated at the GANIL/LISE3 facility by means of charged-particle and $\gamma$-ray spectroscopy. The decay schemes obtained and the Gamow-Teller strength distributions are compared to shell-model calculations based on the USD interaction. B(GT) values derived from the absolute measurement of the $\beta$-decay branching ratios give rise to a quenching factor of the Gamow-Teller strength of 0.6. A precise half-life of 43.7 (6) ms was determined for $^{26}$P, the $\beta$- (2)p decay mode of which is described

Serum, urinary, and salivary nitric oxide in rheumatoid arthritis: complexities of interpreting nitric oxide measures

Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary nitrite and nitrate (NOx) in patients with RA and normal subjects, and we examined the relationships of these measures to disease activity. Serum, urine, and NOx levels as well as renal creatinine, NOx clearance and fractional excretion rates were compared in 25 RA patients and 20 age- and gender-matched healthy controls. Subjects were hospitalized for 3 days and placed on a NOxrestricted diet. NOx was assayed using nitrate reductase and the Griess reagent. RA activity was assessed using standard clinical and laboratory measures. While consuming a restricted diet for 3 days to eliminate the effects of oral intake of NOx, 24 hour urinary NOx excretion decreased in both RA patients and healthy controls. Urine NOx levels at all time points were not significantly different between RA patients and normal subjects. Serum NOx levels also decreased during the 3 days of NOx restriction, but RA patients had higher serum NOx levels at all time points compared with the control group. Likewise, serum NOx/creatinine ratios were higher in RA patients than in controls. Although basal salivary flow rate and tear flow were lower in RA patients, salivary NOx levels did not differ between normal and RA subjects. While renal creatinine clearance was not different between the two groups, we found that RA patients had lower renal NOx clearance and lower renal NOx fractional excretion. After correction of p values for multiple comparisons, there were no significant relationships for the RA group between measures of disease activity and the urinary NOx, serum NOx, or urinary NOx clearance. Despite interest in the use of NO as a marker of disease activity, alterations in renal NOx clearance and fractional excretion in RA make it difficult to assess in vivo NO production even with strict dietary restriction of NOx intake

High index contrast photonic platforms for on-chip Raman spectroscopy

Nanophotonic waveguide enhanced Raman spectroscopy (NWERS) is a sensing technique that uses a highly confined waveguide mode to excite and collect the Raman scattered signal from molecules in close vicinity of the waveguide. The most important parameters defining the figure of merit of an NWERS sensor include its ability to collect the Raman signal from an analyte, i.e. "the Raman conversion efficiency" and the amount of "Raman background" generated from the guiding material. Here, we compare different photonic integrated circuit (PIC) platforms capable of on-chip Raman sensing in terms of the aforementioned parameters. Among the four photonic platforms under study, tantalum oxide and silicon nitride waveguides exhibit high signal collection efficiency and low Raman background. In contrast, the performance of titania and alumina waveguides suffers from a strong Raman background and a weak signal collection efficiency, respectively

The Evaluation of V_{ud}, Experiment and Theory

The value of the V_{ud} matrix element of the Cabibbo-Kobayashi-Maskawa (CKM) matrix can be derived from nuclear superallowed beta decays, neutron decay, and pion beta decay. We survey current world data for all three. Today, the most precise value of V_{ud} comes from the nuclear decays; however, the precision is limited not by experimental error but by the estimated uncertainty in theoretical corrections. Experimental uncertainty does limit the neutron-decay result, which, though statistically consistent with the nuclear result, is approximately a factor of three poorer in precision. The value obtained for $V_{ud}$ leads to a result that differs at the 98% confidence level from the unitarity condition for the CKM matrix. We examine the reliability of the small calculated corrections that have been applied to the data, and assess the likelihood of even higher quality nuclear data becoming available to confirm or deny the discrepancy. Some of the required experiments depend upon the availability of intense radioactive beams. Others are possible today.Comment: 21 pages, 1 figure, LaTe