Transcriptional profiling of degraded RNA in cryopreserved and fixed tissue samples obtained at autopsy

BACKGROUND: Traditional multiplexed gene expression methods require well preserved, intact RNA. Such specimens are difficult to acquire in clinical practice where formalin fixation is the standard procedure for processing tissue. Even when special handling methods are used to obtain frozen tissue, there may be RNA degradation; for example autopsy samples where degradation occurs both pre-mortem and during the interval between death and cryopreservation. Although specimens with partially degraded RNA can be analyzed by qRT-PCR, these analyses can only be done individually or at low levels of multiplexing and are laborious and expensive to run for large numbers of RNA targets. METHODS: We evaluated the ability of the cDNA-mediated Annealing, Selection, extension, and Ligation (DASL) assay to provide highly multiplexed analyses of cryopreserved and formalin fixed, paraffin embedded (FFPE) tissues obtained at autopsy. Each assay provides data on 1536 targets, and can be performed on specimens with RNA fragments as small as 60 bp. RESULTS: The DASL performed accurately and consistently with cryopreserved RNA obtained at autopsy as well as with RNA extracted from formalin-fixed paraffin embedded tissue that had a cryopreserved mirror image specimen with high quality RNA. In FFPE tissue where the cryopreserved mirror image specimen was of low quality the assay performed reproducibly on some but not all specimens. CONCLUSION: The DASL assay provides reproducible results from cryopreserved specimens and many FFPE specimens obtained at autopsy. Gene expression analyses of these specimens may be especially valuable for the study of non-cancer endpoints, where surgical specimens are rarely available

Capsaicin- resistant arterial baroreceptors

BACKGROUND: Aortic baroreceptors (BRs) comprise a class of cranial afferents arising from major arteries closest to the heart whose axons form the aortic depressor nerve. BRs are mechanoreceptors that are largely devoted to cardiovascular autonomic reflexes. Such cranial afferents have either lightly myelinated (A-type) or non-myelinated (C-type) axons and share remarkable cellular similarities to spinal primary afferent neurons. Our goal was to test whether vanilloid receptor (TRPV1) agonists, capsaicin (CAP) and resiniferatoxin (RTX), altered the pressure-discharge properties of peripheral aortic BRs. RESULTS: Periaxonal application of 1 μM CAP decreased the amplitude of the C-wave in the compound action potential conducting at <1 m/sec along the aortic depressor nerve. 10 μM CAP eliminated the C-wave while leaving intact the A-wave conducting in the A-δ range (<12 m/sec). These whole nerve results suggest that TRPV1 receptors are expressed along the axons of C- but not A-conducting BR axons. In an aortic arch – aortic nerve preparation, intralumenal perfusion with 1 μM CAP had no effect on the pressure-discharge relations of regularly discharging, single fiber BRs (A-type) – including the pressure threshold, sensitivity, frequency at threshold, or maximum discharge frequency (n = 8, p > 0.50) but completely inhibited discharge of an irregularly discharging BR (C-type). CAP at high concentrations (10–100 μM) depressed BR sensitivity in regularly discharging BRs, an effect attributed to non-specific actions. RTX (≤ 10 μM) did not affect the discharge properties of regularly discharging BRs (n = 7, p > 0.18). A CAP-sensitive BR had significantly lower discharge regularity expressed as the coefficient of variation than the CAP-resistant fibers (p < 0.002). CONCLUSION: We conclude that functional TRPV1 channels are present in C-type but not A-type (A-δ) myelinated aortic arch BRs. CAP has nonspecific inhibitory actions that are unlikely to be related to TRV1 binding since such effects were absent with the highly specific TRPV1 agonist RTX. Thus, CAP must be used with caution at very high concentrations

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

Mapping Exoplanets

The varied surfaces and atmospheres of planets make them interesting places to live, explore, and study from afar. Unfortunately, the great distance to exoplanets makes it impossible to resolve their disk with current or near-term technology. It is still possible, however, to deduce spatial inhomogeneities in exoplanets provided that different regions are visible at different times---this can be due to rotation, orbital motion, and occultations by a star, planet, or moon. Astronomers have so far constructed maps of thermal emission and albedo for short period giant planets. These maps constrain atmospheric dynamics and cloud patterns in exotic atmospheres. In the future, exo-cartography could yield surface maps of terrestrial planets, hinting at the geophysical and geochemical processes that shape them.Comment: Updated chapter for Handbook of Exoplanets, eds. Deeg & Belmonte. 17 pages, including 6 figures and 4 pages of reference

Adrenal adenomatoid tumor in a patient with human immunodeficiency virus

We present the clinical course of a patient with human immunodeficiency virus and an adrenal adenomatoid tumor (AAT). We describe the clinical course and laboratory, radiographic, and microscopic findings of a patient with human immunodeficiency virus (HIV) and an adenomatoid tumor of the right adrenal gland. A review of the literature was also done via electronic searches through PubMed for articles from 1965 to 2008 that contained the following search terms, adenomatoid tumor limited to the English language only. A 22 year-old African-American male with HIV was incidentally found to have a hypermetabolic right adrenal mass. The patient underwent laparoscopic adrenalectomy and the mass had morphological and immunohistochemical features that were consistent with an AAT. A review of the medical literature reveals that almost all cases of AAT were in male patients (96%) with a mean age of 41±11 years (range=22–64) with no significant difference in laterality (right side=46%, left side=50%, unknown=4%). AAT have an average size of 4.2±3.5 cm (range=0.5–14.3 cm). Pre-operative imaging studies do not appear to be able to reliably distinguish AAT from other types of adrenocortical tumors. For reasons that require further research, AAT typically occur in male patients and may be associated with immunosuppression. AAT can be safely removed laparoscopically with no evidence of long-term recurrence even with tumor extension beyond the adrenal capsule

Measurement of the proton form factor by studying e+e−→ppˉe^{+} e^{-}\rightarrow p\bar{p}

Using data samples collected with the BESIII detector at the BEPCII collider, we measure the Born cross section of $e^{+}e^{-}\rightarrow p\bar{p}$ at 12 center-of-mass energies from 2232.4 to 3671.0 MeV. The corresponding effective electromagnetic form factor of the proton is deduced under the assumption that the electric and magnetic form factors are equal $(|G_{E}|= |G_{M}|)$. In addition, the ratio of electric to magnetic form factors, $|G_{E}/G_{M}|$, and $|G_{M}|$ are extracted by fitting the polar angle distribution of the proton for the data samples with larger statistics, namely at $\sqrt{s}=$ 2232.4 and 2400.0 MeV and a combined sample at $\sqrt{s}$ = 3050.0, 3060.0 and 3080.0 MeV, respectively. The measured cross sections are in agreement with recent results from BaBar, improving the overall uncertainty by about 30\%. The $|G_{E}/G_{M}|$ ratios are close to unity and consistent with BaBar results in the same $q^{2}$ region, which indicates the data are consistent with the assumption that $|G_{E}|=|G_{M}|$ within uncertainties.Comment: 13 pages, 24 figure

Observation of the isospin-violating decay J/ψ→ϕπ0f0(980)J/\psi \to \phi\pi^{0}f_{0}(980)

Using a sample of 1.31 billion $J/\psi$ events collected with the BESIII detector at the BEPCII collider, the decays $J/\psi \to \phi \pi^{+}\pi^{-}\pi^{0}$ and $J/\psi \to \phi \pi^{0}\pi^{0}\pi^{0}$ are investigated. The isospin violating decay $J/\psi \to \phi \pi^{0} f_{0}(980)$ with $f_{0}(980) \to \pi\pi$, is observed for the first time. The width of the $f_{0}(980)$ obtained from the dipion mass spectrum is found to be much smaller than the world average value. In the $\pi^{0} f_{0}(980)$ mass spectrum, there is evidence of $f_1(1285)$ production. By studying the decay $J/\psi \to \phi\eta'$, the branching fractions of $\eta' \to \pi^{+}\pi^{-}\pi^{0}$ and $\eta' \to \pi^{0}\pi^{0}\pi^{0}$, as well as their ratio, are also measured.Comment: 10 pages, 10 figures, published in Phys. Rev.

An amplitude analysis of the π0π0\pi^{0}\pi^{0} system produced in radiative J/ψJ/\psi decays

An amplitude analysis of the $\pi^{0}\pi^{0}$ system produced in radiative $J/\psi$ decays is presented. In particular, a piecewise function that describes the dynamics of the $\pi^{0}\pi^{0}$ system is determined as a function of $M_{\pi^{0}\pi^{0}}$ from an analysis of the $(1.311\pm0.011)\times10^{9}$ $J/\psi$ decays collected by the BESIII detector. The goal of this analysis is to provide a description of the scalar and tensor components of the $\pi^0\pi^0$ system while making minimal assumptions about the properties or number of poles in the amplitude. Such a model-independent description allows one to integrate these results with other related results from complementary reactions in the development of phenomenological models, which can then be used to directly fit experimental data to obtain parameters of interest. The branching fraction of $J/\psi \to \gamma \pi^{0}\pi^{0}$ is determined to be $(1.15\pm0.05)\times10^{-3}$, where the uncertainty is systematic only and the statistical uncertainty is negligible.Comment: Submitted to Phys. Rev. D 19 pages, 4 figure