Some Implications of Believing that Happiness Involves the Absence of Pain: Negative Hedonic Beliefs Exacerbate the Effects of Stress on Well-Being

One common belief about happiness, espoused to varying degrees by both researchers and laypeople alike, is that happiness involves a lack of negative hedonic experiences. In the current investigation, we examine whether individual differences in endorsement of this belief, termed negative hedonic belief, moderate the effects of stress on happiness and several indicators of well-being. It was predicted that because stress involves the experience of negative hedonic states, increased stress would be more robustly associated with decreased happiness and well-being among those endorsing negative hedonic beliefs. Results from three studies utilizing both retrospective and prospective research designs generally support this prediction and suggest that endorsing the belief that happiness involves a lack of negative hedonic experiences is associated with more negative outcomes in response to the experience of heightened life stress

Tissue microarrays: one size does not fit all

<p>Abstract</p> <p>Background</p> <p>Although tissue microarrays (TMAs) are commonly employed in clinical and basic-science research, there are no guidelines for evaluating the appropriateness of a TMA for a given biomarker and tumor type. Furthermore, TMA performance across multiple biomarkers has not been systematically explored.</p> <p>Methods</p> <p>A simulated TMA with between 1 and 10 cores was designed to study tumor expression of 6 biomarkers with varied expression patterns (B7-H1, B7-H3, survivin, Ki-67, CAIX, and IMP3) using 100 patients with clear cell renal cell carcinoma (RCC). We evaluated agreement between whole tissue section and TMA immunohistochemical biomarker quantification to assess how many TMA cores are necessary to adequately represent RCC whole tissue section expression. Additionally, we evaluated associations of whole tissue section and TMA expression with RCC-specific death.</p> <p>Results</p> <p>The number of simulated TMA cores necessary to adequately represent whole tissue section quantification is biomarker specific. Although 2-3 cores appeared adequate for B7-H3, Ki-67, CAIX, and IMP3, even as many as 10 cores resulted in poor agreement for B7-H1 and survivin compared to RCC whole tissue sections. While whole tissue section B7-H1 was significantly associated with RCC-specific death, no significant associations were detected using as many as 10 TMA cores, suggesting that TMAs can result in false-negative findings if the TMA is not optimally designed.</p> <p>Conclusions</p> <p>Prior to TMA analysis, the number of TMA cores necessary to accurately represent biomarker expression on whole tissue sections should be established as there is not a one-size-fits-all TMA. We illustrate the use of a simulated TMA as a cost-effective tool for this purpose.</p

The pathogenic role of c‑Kit+ mast cells in the spinal motor neuron‑vascular niche in ALS

Degeneration of motor neurons, glial cell reactivity, and vascular alterations in the CNS are important neuropathological features of amyotrophic lateral sclerosis (ALS). Immune cells trafficking from the blood also infiltrate the affected CNS parenchyma and contribute to neuroinflammation. Mast cells (MCs) are hematopoietic-derived immune cells whose precursors differentiate upon migration into tissues. Upon activation, MCs undergo degranulation with the ability to increase vascular permeability, orchestrate neuroinflammation and modulate the neuroimmune response. However, the prevalence, pathological significance, and pharmacology of MCs in the CNS of ALS patients remain largely unknown. In autopsy ALS spinal cords, we identified for the first time that MCs express c-Kit together with chymase, tryptase, and Cox-2 and display granular or degranulating morphology, as compared with scarce MCs in control cords. In ALS, MCs were mainly found in the niche between spinal motor neuron somas and nearby microvascular elements, and they displayed remarkable pathological abnormalities. Similarly, MCs accumulated in the motor neuron-vascular niche of ALS murine models, in the vicinity of astrocytes and motor neurons expressing the c-Kit ligand stem cell factor (SCF), suggesting an SCF/c-Kit-dependent mechanism of MC differentiation from precursors. Mechanistically, we provide evidence that fully differentiated MCs in cell cultures can be generated from the murine ALS spinal cord tissue, further supporting the presence of c-Kit+ MC precursors. Moreover, intravenous administration of bone marrow-derived c-Kit+ MC precursors infiltrated the spinal cord in ALS mice but not in controls, consistent with aberrant trafficking through a defective microvasculature. Pharmacological inhibition of c-Kit with masitinib in ALS mice reduced the MC number and the influx of MC precursors from the periphery. Our results suggest a previously unknown pathogenic mechanism triggered by MCs in the ALS motor neuron-vascular niche that might be targeted pharmacologically

Evolution of variants of yeast site-specific recombinase Flp that utilize native genomic sequences as recombination target sites

As a tool in directed genome manipulations, site-specific recombination is a double-edged sword. Exquisite specificity, while highly desirable, makes it imperative that the target site be first inserted at the desired genomic locale before it can be manipulated. We describe a combination of computational and experimental strategies, based on the tyrosine recombinase Flp and its target site FRT, to overcome this impediment. We document the systematic evolution of Flp variants that can utilize, in a bacterial assay, two sites from the human interleukin 10 gene, IL10, as recombination substrates. Recombination competence on an end target site is acquired via chimeric sites containing mixed sequences from FRT and the genomic locus. This is the first time that a tyrosine site-specific recombinase has been coaxed successfully to perform DNA exchange within naturally occurring sequences derived from a foreign genomic context. We demonstrate the ability of an Flp variant to mediate integration of a reporter cassette in Escherichia coli via recombination at one of the IL10-derived sites

Genome-wide analysis of DNA methylation patterns in horse

Background: DNA methylation is an epigenetic regulatory mechanism that plays an essential role in mediating biological processes and determining phenotypic plasticity in organisms. Although the horse reference genome and whole transcriptome data are publically available the global DNA methylation data are yet to be known. Results: We report the first genome-wide DNA methylation characteristics data from skeletal muscle, heart, lung, and cerebrum tissues of thoroughbred (TH) and Jeju (JH) horses, an indigenous Korea breed, respectively by methyl-DNA immunoprecipitation sequencing. The analysis of the DNA methylation patterns indicated that the average methylation density was the lowest in the promoter region, while the density in the coding DNA sequence region was the highest. Among repeat elements, a relatively high density of methylation was observed in long interspersed nuclear elements compared to short interspersed nuclear elements or long terminal repeat elements. We also successfully identified differential methylated regions through a comparative analysis of corresponding tissues from TH and JH, indicating that the gene body regions showed a high methylation density. Conclusions: We provide report the first DNA methylation landscape and differentially methylated genomic regions (DMRs) of thoroughbred and Jeju horses, providing comprehensive DMRs maps of the DNA methylome. These data are invaluable resource to better understanding of epigenetics in the horse providing information for the further biological function analyses.open1

Early Planet Formation in Embedded Disks (eDisk). VIII. A Small Protostellar Disk around the Extremely Low-Mass and Young Class 0 Protostar, IRAS 15398-3359

Protostellar disks are a ubiquitous part of the star formation process and the future sites of planet formation. As part of the Early Planet Formation in Embedded Disks (eDisk) large program, we present high-angular resolution dust continuum ($\sim40\,$mas) and molecular line ($\sim150\,$mas) observations of the Class 0 protostar, IRAS 15398-3359. The dust continuum is small, compact, and centrally peaked, while more extended dust structures are found in the outflow directions. We perform a 2D Gaussian fitting to find the deconvolved size and $2\sigma$ radius of the dust disk to be $4.5\times2.8\,\mathrm{au}$ and $3.8\,\mathrm{au}$, respectively. We estimate the gas+dust disk mass assuming optically thin continuum emission to be $0.6-1.8\,M_\mathrm{jup}$, indicating a very low-mass disk. The CO isotopologues trace components of the outflows and inner envelope, while SO traces a compact, rotating disk-like component. Using several rotation curve fittings on the PV diagram of the SO emission, the lower limits of the protostellar mass and gas disk radius are $0.022\,M_\odot$ and $31.2\,\mathrm{au}$ from our Modified 2 single power-law fitting. A conservative upper limit of the protostellar mass is inferred to be $0.1\,M_\odot$. The protostellar mass-accretion rate and the specific angular momentum at the protostellar disk edge are found to be between $1.3-6.1\times10^{-6}\,M_\odot\,\mathrm{yr^{-1}}$ and $1.2-3.8\times10^{-4}\,\mathrm{km\,s^{-1}\,pc}$, respectively, with an age estimated between $0.4-7.5\times10^{4}\,$yr. At this young age with no clear substructures in the disk, planet formation would likely not yet have started. This study highlights the importance of high-resolution observations and systematic fitting procedures when deriving dynamical properties of deeply embedded Class 0 protostars.Comment: 28 pages, 16 figures. Accepted for publication in ApJ as one of the first-look papers of the eDisk ALMA Large Progra

Early Planet Formation in Embedded Disks (eDisk) VI: Kinematic Structures around the Very Low Mass Protostar IRAS 16253-2429

Precise estimates of protostellar masses are crucial to characterize the formation of stars of low masses down to brown-dwarfs (BDs; M* < 0.08 Msun). The most accurate estimation of protostellar mass uses the Keplerian rotation in the circumstellar disk around the protostar. To apply the Keplerian rotation method to a protostar at the low-mass end, we have observed the Class 0 protostar IRAS 16253-2429 using the Atacama Large Millimeter/submillimeter Array (ALMA) in the 1.3 mm continuum at an angular resolution of 0.07" (10 au), and in the 12CO, C18O, 13CO (J=2-1), and SO (J_N = 6_5-5_4) molecular lines, as part of the ALMA Large Program Early Planet Formation in Embedded Disks (eDisk). The continuum emission traces a non-axisymmetric, disk-like structure perpendicular to the associated 12CO outflow. The position-velocity (PV) diagrams in the C18O and 13CO lines can be interpreted as infalling and rotating motions. In contrast, the PV diagram along the major axis of the disk-like structure in the 12CO line allows us to identify Keplerian rotation. The central stellar mass and the disk radius are estimated to be ~0.12-0.17 Msun and ~13-19 au, respectively. The SO line suggests the existence of an accretion shock at a ring (r~28 au) surrounding the disk and a streamer from the eastern side of the envelope. IRAS 16253-2429 is not a proto-BD but has a central stellar mass close to the BD mass regime, and our results provide a typical picture of such very low-mass protostars.Comment: 41 pages, 14 figure

Early Planet Formation in Embedded Disks (eDisk) V: Possible Annular Substructure in a Circumstellar Disk in the Ced110 IRS4 System

We have observed the Class 0/I protostellar system Ced110 IRS4 at an angular resolution of $0.05''$ ($\sim$10 au) as a part of the ALMA large program; Early Planet Formation in the Embedded Disks (eDisk). The 1.3 mm dust continuum emission reveals that Ced110 IRS4 is a binary system with a projected separation of $\sim$250 au. The continuum emissions associated with the main source and its companion, named Ced110 IRS4A and IRS4B respectively, exhibit disk-like shapes and likely arise from dust disks around the protostars. The continuum emission of Ced110 IRS4A has a radius of $\sim$110 au ($\sim0.6''$), and shows bumps along its major axis with an asymmetry. The bumps can be interpreted as an shallow, ring-like structure at a radius of $\sim$40 au ($\sim0.2''$) in the continuum emission, as demonstrated from two-dimensional intensity distribution models. A rotation curve analysis on the C$^{18}$O and $^{13}$CO $J=2$-1 lines reveals the presence of a Keplerian disk within a radius of 120 au around Ced110 IRS4A, which supports the interpretation that the dust continuum emission arises from a disk. The ring-like structure in the dust continuum emission might indicate a possible, annular substructure in the surface density of the embedded disk, although the possibility that it is an apparent structure due to the optically thick continuum emission cannot be ruled out.Comment: 32 pages, 23 figures. Accepted for publication in ApJ as one of the first-look papers of the eDisk ALMA Large Progra

Early Planet Formation in Embedded Disks (eDisk). II. Limited Dust Settling and Prominent Snow Surfaces in the Edge-on Class I Disk IRAS 04302+2247

While dust disks around optically visible, Class II protostars are found to be vertically thin, when and how dust settles to the midplane are unclear. As part of the Atacama Large Millimeter/submillimeter Array (ALMA) large program, Early Planet Formation in Embedded Disks, we analyze the edge-on, embedded, Class I protostar IRAS 04302+2247, also nicknamed the ``Butterfly Star." With a resolution of 0.05" (8~au), the 1.3 mm continuum shows an asymmetry along the minor axis which is evidence of an optically thick and geometrically thick disk viewed nearly edge-on. There is no evidence of rings and gaps, which could be due to the lack of radial substructure or the highly inclined and optically thick view. With 0.1" (16~au) resolution, we resolve the 2D snow surfaces, i.e., the boundary region between freeze-out and sublimation, for $^{12}$CO $J$=2--1, $^{13}$CO $J$=2--1, C$^{18}$O $J$=2--1, $H_{2}$CO $J$=$3_{0,3}$--$2_{0,2}$, and SO $J$=$6_{5}$--$5_{4}$, and constrain the CO midplane snow line to $\sim 130$ au. We find Keplerian rotation around a protostar of $1.6 \pm 0.4 M_{\odot}$ using C$^{18}$O. Through forward ray-tracing using RADMC-3D, we find that the dust scale height is $\sim 6$ au at a radius of 100~au from the central star and is comparable to the gas pressure scale height. The results suggest that the dust of this Class~I source has yet to vertically settle significantly.Comment: 33 pages, 21 figures. Accepted for publication in ApJ as one of the first-look papers of the eDisk ALMA Large Progra

Early Planet Formation in Embedded Disks (eDisk) XII: Accretion streamers, protoplanetary disk, and outflow in the Class I source Oph IRS63

We present ALMA observations of the Class I source Oph IRS63 in the context of the Early Planet Formation in Embedded Disks (eDisk) large program. Our ALMA observations of Oph IRS63 show a myriad of protostellar features, such as a shell-like bipolar outflow (in $^{12}$CO), an extended rotating envelope structure (in $^{13}$CO), a streamer connecting the envelope to the disk (in C$^{18}$O), and several small-scale spiral structures seen towards the edge of the dust continuum (in SO). By analyzing the velocity pattern of $^{13}$CO and C$^{18}$O, we measure a protostellar mass of $\rm M_\star = 0.5 \pm 0.2$~$\rm M_\odot$ and confirm the presence of a disk rotating at almost Keplerian velocity that extends up to $\sim260$ au. These calculations also show that the gaseous disk is about four times larger than the dust disk, which could indicate dust evolution and radial drift. Furthermore, we model the C$^{18}$O streamer and SO spiral structures as features originating from an infalling rotating structure that continuously feeds the young protostellar disk. We compute an envelope-to-disk mass infall rate of $\sim 10^{-6}$~$\rm M_\odot \, yr^{-1}$ and compare it to the disk-to-star mass accretion rate of $\sim 10^{-8}$~$\rm M_\odot \, yr^{-1}$, from which we infer that the protostellar disk is in a mass build-up phase. At the current mass infall rate, we speculate that soon the disk will become too massive to be gravitationally stable.Comment: 26 pages and 17 figure