Neuroimmune Crosstalk: A Role for Neuropeptide Y in Inflammatory Bowel Disease

Neuropeptide Y (NPY) is a 36-amino acid peptide widely expressed in the central and peripheral nervous systems. In addition to other cells, NPY is also synthesized and co-released from sympathetic nerve fibers functioning as a potent sympathetic neuromodulator. NPY has been implicated in playing important roles in the regulation of energy balance, appetite, anxiety, vascular tone, and immune cell functioning. In addition, immune cells of both the innate and adaptive immune systems express functional NPY receptors. Some immune cells can produce and secrete NPY, and genetic alteration of these receptors results in altered immune cell functioning. Its direct association with the immune system, its presence in sympathetic neurons innervating primary and secondary immune organs and its close association with vasculature, make NPY a candidate for mediating, at least in part, the neuroimmune crosstalk. The gene expression results presented here suggest that DSS is a valid model of human IBD and that pain-related behavior in the open field is closely associated with DSS-induced gene changes. Furthermore, the data suggest that NPY signaling via its Y1 receptor plays some regulatory role in the immune process induced by DSS. Y2 receptor antagonism resulted in a mild attenuation of immune activity but also slightly attenuated pain-related behavior in the open field. In sum, it appears that NPY signaling via its Y1 and Y2 receptors plays a role in various features of DSS induced disease

Search for nearby stars among proper motion stars selected by optical-to-infrared photometry. I. Discovery of LHS 2090 at spectroscopic distance of d=6pc

We present the discovery of a previously unknown very nearby star - LHS 2090 at a distance of only d=6 pc. In order to find nearby (i.e. d < 25 pc) red dwarfs, we re-identified high proper motion stars ($\mu >$ 0.18 arcsec/yr) from the NLTT catalogue (Luyten \cite{luyten7980}) in optical Digitized Sky Survey data for two different epochs and in the 2MASS data base. Only proper motion stars with large $R-K_s$ colour index and with relatively bright infrared magnitudes ($K_s<10$) were selected for follow-up spectroscopy. The low-resolution spectrum of LHS 2090 and its large proper motion (0.79 arcsec/yr) classify this star as an M6.5 dwarf. The resulting spectroscopic distance estimate from comparing the infrared $JHK_s$ magnitudes of LHS 2090 with absolute magnitudes of M6.5 dwarfs is $6.0\pm1.1$ pc assuming an uncertainty in absolute magnitude of $\pm$0.4 mag.Comment: 3 pages, 1 figure, accepted for publication in Astronomy and Astrophysics Letter

The Solar Neighborhood XV: Discovery of New High Proper Motion Stars with mu >= 0.4"/yr between Declinations -47 degrees and 00 degrees

We report the discovery of 152 new high proper motion systems (mu >= 0.4"/yr) in the southern sky (Declination = -47 degrees to 00 degrees) brighter than UKST plate R_{59F} =16.5 via our SuperCOSMOS-RECONS (SCR) search. This paper complements Paper XII in The Solar Neighborhood series, which covered the region from Declination = -90 degrees to -47 degrees and discussed all 147 new systems from the southernmost phase of the search. Among the total of 299 systems from both papers, there are 148 (71 in Paper XII, 77 in this paper) new systems moving faster than 0.5"/yr that are additions to the classic ``LHS'' (Luyten Half Second) sample. These constitute an 8% increase in the sample of all stellar systems with mu >= 0.5"/yr in the southern sky. As in Paper XII, distance estimates are provided for the systems reported here based upon a combination of photographic plate magnitudes and 2MASS photometry, assuming all stars are on the main sequence. Two SCR systems from the portion of the sky included in this paper are anticipated to be within 10 pc, and an additional 23 are within 25 pc. In total, the results presented in Paper XII and here for this SCR sweep of the entire southern sky include five new systems within 10 pc and 38 more between 10 and 25 pc. The largest number of nearby systems have been found in the slowest proper motion bin, 0.6"/yr > mu >= 0.4"/yr, indicating that there may be a large population of low proper motion systems very near the Sun.Comment: 36 pages, 5 figures, accepted for publication in Astronomical Journa

Behavioral and Neuroanatomical Abnormalities in Pleiotrophin Knockout Mice

Pleiotrophin (PTN) is an extracellular matrix-associated protein with neurotrophic and neuroprotective effects that is involved in a variety of neurodevelopmental processes. Data regarding the cognitive-behavioral and neuroanatomical phenotype of pleiotrophin knockout (KO) mice is limited. The purpose of this study was to more fully characterize this phenotype, with emphasis on the domains of learning and memory, cognitive-behavioral flexibility, exploratory behavior and anxiety, social behavior, and the neuronal and vascular microstructure of the lateral entorhinal cortex (EC). PTN KOs exhibited cognitive rigidity, heightened anxiety, behavioral reticence in novel contexts and novel social interactions suggestive of neophobia, and lamina-specific decreases in neuronal area and increases in neuronal density in the lateral EC. Initial learning of spatial and other associative tasks, as well as vascular density in the lateral EC, was normal in the KOs. These data suggest that the absence of PTN in vivo is associated with disruption of specific cognitive and affective processes, raising the possibility that further study of PTN KOs might have implications for the study of human disorders with similar features

Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism.

OBJECTIVE: Brown adipose tissue (BAT) thermogenesis is critical in maintaining body temperature. The dorsomedial hypothalamus (DMH) integrates cutaneous thermosensory signals and regulates adaptive thermogenesis. Here, we study the function and synaptic connectivity of input from DMH cholinergic neurons to sympathetic premotor neurons in the raphe pallidus (Rpa). METHODS: In order to selectively manipulate DMH cholinergic neuron activity, we generated transgenic mice expressing channelrhodopsin fused to yellow fluorescent protein (YFP) in cholinergic neurons (choline acetyltransferase (ChAT)-Cre::ChR2-YFP) with the Cre-LoxP technique. In addition, we used an adeno-associated virus carrying the Cre recombinase gene to delete the floxed Chat gene in the DMH. Physiological studies in response to optogenetic stimulation of DMH cholinergic neurons were combined with gene expression and immunocytochemical analyses. RESULTS: A subset of DMH neurons are ChAT-immunopositive neurons. The activity of these neurons is elevated by warm ambient temperature. A phenotype-specific neuronal tracing shows that DMH cholinergic neurons directly project to serotonergic neurons in the Rpa. Optical stimulation of DMH cholinergic neurons decreases BAT activity, which is associated with reduced body core temperature. Furthermore, elevated DMH cholinergic neuron activity decreases the expression of BAT uncoupling protein 1 (Ucp1) and peroxisome proliferator-activated receptor γ coactivator 1 α (Pgc1α) mRNAs, markers of BAT activity. Injection of M2-selective muscarinic receptor antagonists into the 4th ventricle abolishes the effect of optical stimulation. Single cell qRT-PCR analysis of retrogradely identified BAT-projecting neurons in the Rpa shows that all M2 receptor-expressing neurons contain tryptophan hydroxylase 2. In animals lacking the Chat gene in the DMH, exposure to warm temperature reduces neither BAT Ucp1 nor Pgc1α mRNA expression. CONCLUSION: DMH cholinergic neurons directly send efferent signals to sympathetic premotor neurons in the Rpa. Elevated cholinergic input to this area reduces BAT activity through activation of M2 mAChRs on serotonergic neurons. Therefore, the direct DMH(ACh)-Rpa(5-HT) pathway may mediate physiological heat-defense responses to elevated environmental temperature.We thank Althea Cavanaugh and Licheng Wu for technical supports. This work was supported by NIDDK (RO1DK092246) to Y.-H.J. and New York obesity nutrition research center to J.H.J.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S2212877815000617

The Solar Neighborhood XII: Discovery of New High Proper Motion Stars with 1.0"/yr > mu >= 0.4"/yr between Declinations -90 degrees and -47 degrees

We report the discovery of 141 new high proper motion systems (1.0"/yr > mu >= 0.4"/yr) in the southern sky (Declination = -90 degrees to -47 degrees) brighter than UKST plate R_{59F} = 16.5 via our SuperCOSMOS-RECONS (SCR) search. When combined with the nine systems having mu >= 1.0"/yr and/or late spectral type from the initial phases of this effort (Hambly et al. 2004, Henry et al. 2004), we find that 73 of the 150 total systems are moving faster than 0.5"/yr, and are therefore new members of the classic "LHS" (Luyten Half Second) sample. These constitute a 21% increase in the sample of stars with mu >= 0.5"/yr in the declination region searched, thereby comprising an important addition to this long-neglected region of the sky. Distance estimates are provided for the entire sample, based upon a combination of photographic plate magnitudes and 2MASS photometry, using the relations presented in Hambly et al. (2004) for the presumed main sequence stars. Three systems are anticipated to be within 10 pc, and an additional 15 are within 25 pc. Eight of these 18 nearby systems have proper motions falling between 0.4"/yr and 0.6"/yr, hinting at a large population of nearby stars with fast, but not extremely high, proper motions that have not been thoroughly investigated.Comment: 45 pages, 6 figures, accepted for publication in Astronomical Journal (January 2005

A Hot Uranus Orbiting the Super Metal-rich Star HD77338 and the Metallicity - Mass Connection

We announce the discovery of a low-mass planet orbiting the super metal-rich K0V star HD77338 as part of our on-going Calan-Hertfordshire Extrasolar Planet Search. The best fit planet solution has an orbital period of 5.7361\pm0.0015 days and with a radial velocity semi-amplitude of only 5.96\pm1.74 m/s, we find a minimum mass of 15.9+4.7-5.3 Me. The best fit eccentricity from this solution is 0.09+0.25-0.09, and we find agreement for this data set using a Bayesian analysis and a periodogram analysis. We measure a metallicity for the star of +0.35\pm0.06 dex, whereas another recent work (Trevisan et al. 2011) finds +0.47\pm0.05 dex. Thus HD77338b is one of the most metal-rich planet host stars known and the most metal-rich star hosting a sub-Neptune mass planet. We searched for a transit signature of HD77338b but none was detected. We also highlight an emerging trend where metallicity and mass seem to correlate at very low masses, a discovery that would be in agreement with the core accretion model of planet formation. The trend appears to show that for Neptune-mass planets and below, higher masses are preferred when the host star is more metal-rich. Also a lower boundary is apparent in the super metal-rich regime where there are no very low-mass planets yet discovered in comparison to the sub-solar metallicity regime. A Monte Carlo analysis shows that this, low-mass planet desert, is statistically significant with the current sample of 36 planets at around the 4.5\sigma\ level. In addition, results from Kepler strengthen the claim for this paucity of the lowest-mass planets in super metal-rich systems. Finally, this discovery adds to the growing population of low-mass planets around low-mass and metal-rich stars and shows that very low-mass planets can now be discovered with a relatively small number of data points using stable instrumentation.Comment: 25 pages, 15 figures, 5 tables, accepted for publication in Ap

Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage

Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer?s disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease.FUNDING: Acknowledgements The authors are grateful to the participants in the Religious Order Study, the Memory and Aging Project. Z.C. and R.H.R. were supported by grants from the Leonard Wolfson Foundation. M.R. was supported by the United Kingdom Medical Research Council (MRC) through the award of a Tenure Track Clinician Scientist Fellowship (MR/ N008324/1). J.H. was supported by the UK Dementia Research Institute which receives its funding from DRI Limited, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. J.H. has also been funded by the Medical Research Council (award MR/N026004/1), Wellcome Trust (award 202903/Z/16/Z), Dolby Family Fund and National Institute for Health Research University College London Hospitals Biomedical Research Centre. J.B. is supported through the Science and Technology Agency, Séneca Foundation, CARM, Spain (research project 00007/COVI/20)

Hepatitis B Sero-Prevalence and Risk Behaviors Among Immigrant Men in a Population-Based Household Survey in Low-Income Neighborhoods of Northern California

Background Despite an effective vaccine, 60,000 new HBV infections were reported in the US in 2004; 95% in adults. We evaluate HBV sero-prevalence, risk behaviors and self-reported vaccination among Latino immigrant, Asian immigrant and US born low income men in five northern California counties. Methods Population based, cross sectional survey of HBV sero-prevalence and risk behaviors in men aged 18 to 35 years. Results Among 1,512 men screened, Asian immigrants were most likely to have had prior HBV infection (15.1%) and chronic infection (3.8%) compared to US born (prior 5.1%, chronic 0.6%) and Latino immigrant men (prior 2.0%, chronic 0.3%.) Reported HBV vaccination was lowest for Latino immigrants (12%) compared to Asian immigrants and US born men (35% in both.) Latino immigrants reported less educational attainment, medical insurance coverage and access to a physician in the last six months. Discussion Healthcare providers should routinely screen Asian immigrants for HBV regardless of their self reported vaccination status. Latino immigrants may comprise an important group of under-vaccinated, at risk persons in California. HBV testing and vaccination of immigrants soon after US arrival should be encouraged