Culture in Reduced Levels of Oxygen Promotes Clonogenic Sympathoadrenal Differentiation by Isolated Neural Crest Stem Cells

Isolated neural crest stem cells (NCSCs) differentiate to autonomic neurons in response to bone morphogenetic protein 2 (BMP2) in clonal cultures, but these neurons do not express sympathoadrenal (SA) lineage markers. Whether this reflects a developmental restriction in NCSCs or simply inappropriate culture conditions was not clear. We tested the growth and differentiation potential of NCSCs at ∼5% O_2, which more closely approximates physiological oxygen levels. Eighty-three percent of p75^+P_0 ^− cells isolated from embryonic day 14.5 sciatic nerve behaved as stem cells under these conditions, suggesting that this is a nearly pure population. Furthermore, addition of BMP2 plus forskolin in decreased oxygen cultures elicited differentiation of thousands of cells expressing tyrosine hydroxylase, dopamine-β-hydroxylase, and the SA lineage marker SA-1 in nearly all colonies. Such cells also synthesized and released dopamine and norepinephrine. These data demonstrate that isolated mammalian NCSCs uniformly possess SA lineage capacity and further suggest that oxygen levels can influence cell fate. Parallel results indicating that reduced oxygen levels can also promote the survival, proliferation, and catecholaminergic differentiation of CNS stem cells (Studer et al., 2000) suggests that neural stem cells may exhibit a conserved response to reduced oxygen levels

Dissecting the regulatory activity and sequence content of loci with exceptional numbers of transcription factor associations

DNA-associated proteins (DAPs) classically regulate gene expression by binding to regulatory loci such as enhancers or promoters. As expanding catalogs of genome-wide DAP binding maps reveal thousands of loci that, unlike the majority of conventional enhancers and promoters, associate with dozens of different DAPs with apparently little regard for motif preference, an understanding of DAP association and coordination at such regulatory loci is essential to deciphering how these regions contribute to normal development and disease. In this study, we aggregated publicly available ChIP-seq data from 469 human DAPs assayed in three cell lines and integrated these data with an orthogonal data set of 352 nonredundant, in vitro–derived motifs mapped to the genome within DNase I hypersensitivity footprints to characterize regions with high numbers of DAP associations. We establish a generalizable definition for high occupancy target (HOT) loci and identify putative driver DAP motifs in HepG2 cells, including HNF4A, SP1, SP5, and ETV4, that are highly prevalent and show sequence conservation at HOT loci. The number of different DAPs associated with an element is positively associated with evidence of regulatory activity, and by systematically mutating 245 HOT loci with a massively parallel mutagenesis assay, we localized regulatory activity to a central core region that depends on the motif sequences of our previously nominated driver DAPs. In sum, this work leverages the increasingly large number of DAP motif and ChIP-seq data publicly available to explore how DAP associations contribute to genome-wide transcriptional regulation

Beautiful friendship: Social sharing of emotions improves subjective feelings and activates the neural reward circuitry

Humans have a strong tendency to affiliate with other people, especially in emotional situations. Here, we suggest that a critical mechanism underlying this tendency is that socially sharing emotional experiences is in itself perceived as hedonically positive and thereby contributes to the regulation of individual emotions. We investigated the effect of social sharing of emotions on subjective feelings and neural activity by having pairs of friends view emotional (negative and positive) and neutral pictures either alone or with the friend. While the two friends remained physically separated throughout the experiment—with one undergoing functional magnetic resonance imaging and the other performing the task in an adjacent room—they were made aware on a trial-by-trial basis whether they were seeing pictures simultaneously with their friend (shared) or alone (unshared). Ratings of subjective feelings were improved significantly when participants viewed emotional pictures together than alone, an effect that was accompanied by activity increase in ventral striatum and medial orbitofrontal cortex, two important components of the reward circuitry. Because these effects occurred without any communication or interaction between the friends, they point to an important proximate explanation for the basic human motivation to affiliate with others, particularly in emotional situation

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Dissecting the regulatory activity and sequence content of loci with exceptional numbers of transcription factor associations

DNA-associated proteins (DAPs) classically regulate gene expression by binding to regulatory loci such as enhancers or promoters. As expanding catalogs of genome-wide DAP binding maps reveal thousands of loci that, unlike the majority of conventional enhancers and promoters, associate with dozens of different DAPs with apparently little regard for motif preference, an understanding of DAP association and coordination at such regulatory loci is essential to deciphering how these regions contribute to normal development and disease. In this study, we aggregated publicly available ChIP-seq data from 469 human DAPs assayed in three cell lines and integrated these data with an orthogonal data set of 352 nonredundant, in vitro–derived motifs mapped to the genome within DNase I hypersensitivity footprints to characterize regions with high numbers of DAP associations. We establish a generalizable definition for high occupancy target (HOT) loci and identify putative driver DAP motifs in HepG2 cells, including HNF4A, SP1, SP5, and ETV4, that are highly prevalent and show sequence conservation at HOT loci. The number of different DAPs associated with an element is positively associated with evidence of regulatory activity, and by systematically mutating 245 HOT loci with a massively parallel mutagenesis assay, we localized regulatory activity to a central core region that depends on the motif sequences of our previously nominated driver DAPs. In sum, this work leverages the increasingly large number of DAP motif and ChIP-seq data publicly available to explore how DAP associations contribute to genome-wide transcriptional regulation

Beautiful friendship: Social sharing of emotions improves subjective feelings and activates the neural reward circuitry

Humans have a strong tendency to affiliate with other people, especially in emotional situations. Here, we suggest that a critical mechanism underlying this tendency is that socially sharing emotional experiences is in itself perceived as hedonically positive and thereby contributes to the regulation of individual emotions. We investigated the effect of social sharing of emotions on subjective feelings and neural activity by having pairs of friends view emotional (negative and positive) and neutral pictures either alone or with the friend. While the two friends remained physically separated throughout the experiment—with one undergoing functional magnetic resonance imaging and the other performing the task in an adjacent room—they were made aware on a trial-by-trial basis whether they were seeing pictures simultaneously with their friend (shared) or alone (unshared). Ratings of subjective feelings were improved significantly when participants viewed emotional pictures together than alone, an effect that was accompanied by activity increase in ventral striatum and medial orbitofrontal cortex, two important components of the reward circuitry. Because these effects occurred without any communication or interaction between the friends, they point to an important proximate explanation for the basic human motivation to affiliate with others, particularly in emotional situations

The learning curve associated with the introduction of the subcutaneous implantable defibrillator

Aims: The subcutaneous implantable cardioverter defibrillator (S-ICD) was introduced to overcome complications related to transvenous leads. Adoption of the S-ICD requires implanters to learn a new implantation technique. The aim of this study was to assess the learning curve for S-ICD implanters with respect to implant-related complications, procedure time, and inappropriate shocks (IASs). Methods and results: In a pooled cohort from two clinical S-ICD databases, the IDE Trial and the EFFORTLESS Registry, complications, IASs at 180 days follow-up and implant procedure duration were assessed. Patients were grouped in quartiles based on experience of the implanter and Kaplan-Meier estimates of complication and IAS rates were calculated. A total of 882 patients implanted in 61 centres by 107 implanters with a median of 4 implants (IQR 1,8) were analysed. There were a total of 59 patients with complications and 48 patients with IAS. The complication rate decreased significantly from 9.8% in Quartile 1 (least experience) to 5.4% in Quartile 4 (most experience) (P = 0.02) and non-significantly for IAS from 7.9 to 4.8% (P = 0.10). Multivariable analysis demonstrated a hazard ratio of 0.78 (P = 0.045) for complications and 1.01 (P = 0.958) for IAS. Dual-zone programming increased with experience of the individual implanter (P 13 implants). Conclusion: There is a short and significant learning curve associated with physicians adopting the S-ICD. Performance stab

The Human Touch: Skin Temperature During the Rubber Hand Illusion in Manual and Automated Stroking Procedures

Rohde M, Wold A, Karnath H-O, Ernst MO. The Human Touch: Skin Temperature During the Rubber Hand Illusion in Manual and Automated Stroking Procedures. PLoS ONE. 2013;8(11): e80688.A difference in skin temperature between the hands has been identified as a physiological correlate of the rubber hand illusion (RHI). The RHI is an illusion of body ownership, where participants perceive body ownership over a rubber hand if they see it being stroked in synchrony with their own occluded hand. The current study set out to replicate this result, i.e., psychologically induced cooling of the stimulated hand using an automated stroking paradigm, where stimulation was delivered by a robot arm (PHANToMTM force-feedback device). After we found no evidence for hand cooling in two experiments using this automated procedure, we reverted to a manual stroking paradigm, which is closer to the one employed in the study that first produced this effect. With this procedure, we observed a relative cooling of the stimulated hand in both the experimental and the control condition. The subjective experience of ownership, as rated by the participants, by contrast, was strictly linked to synchronous stroking in all three experiments. This implies that hand-cooling is not a strict correlate of the subjective feeling of hand ownership in the RHI. Factors associated with the differences between the two designs (differences in pressure of tactile stimulation, presence of another person) that were thus far considered irrelevant to the RHI appear to play a role in bringing about this temperature effect

The AEPEX Mission: Imaging Energetic Particle Precipitation in the Atmosphere through its Bremsstrahlung X-ray Signatures

The Atmospheric Effects of Precipitation through Energetic X-rays (AEPEX) mission is a 6U CubeSat that will monitor energetic electron precipitation from the radiation belts into the upper atmosphere. The primary instrument will image energetic (50&ndash;300 keV) X-rays produced in the atmosphere by bremsstrahlung, providing a near-direct signature of electron precipitation. An energetic electron detector will measure the precipitating electron spectrum, while the X-ray observations will be used to determine the absolute flux. X-ray images will be produced with 10-s time resolution and 50&ndash;100 km spatial resolution. The 6U spacecraft uses flight heritage spacecraft bus subsystems, including the attitude determination and control, electrical power, and command &amp; data handling systems. AEPEX is designed to be operated from low-Earth orbit at ~500 km altitude with a high inclination in order to cover the outer radiation belt. AEPEX will be the first spacecraft mission to measure X-rays in the 50&ndash;300 keV energy range emitted by Earth&rsquo;s atmosphere in response to radiation belt precipitation, and the first to image that precipitation from above.</p

SN 2022joj: A Peculiar Type Ia Supernova Possibly Driven by an Asymmetric Helium-shell Double Detonation

We present observations of SN 2022joj, a peculiar Type Ia supernova (SN Ia) discovered by the Zwicky Transient Facility (ZTF). SN 2022joj exhibits an unusually red $g_\mathrm{ZTF}-r_\mathrm{ZTF}$ color at early times and a rapid blueward evolution afterwards. Around maximum brightness, SN 2022joj shows a high luminosity ($M_{g_\mathrm{ZTF},\mathrm{max}}\simeq-19.7$ mag), a blue broadband color ($g_\mathrm{ZTF}-r_\mathrm{ZTF}\simeq-0.2$ mag), and shallow Si II absorption lines, consistent with those of overluminous, SN 1991T-like events. The maximum-light spectrum also shows prominent absorption around 4200 \r{A}, which resembles the Ti II features in subluminous, SN 1991bg-like events. Despite the blue optical-band colors, SN 2022joj exhibits extremely red ultraviolet $-$ optical colors at maximum luminosity ($u-v\simeq1.6$ mag and $uvw1 - v\simeq4.0$ mag), suggesting a suppression of flux between $\sim$2500--4000 \r{A}. Strong C II lines are also detected at peak. We show that these unusual spectroscopic properties are broadly consistent with the helium-shell double detonation of a sub-Chandrasekhar mass ($M\simeq1\mathrm{M_\odot}$) carbon/oxygen (C/O) white dwarf (WD) from a relatively massive helium shell ($M_s\simeq0.04$--$0.1\mathrm{M_\odot}$), if observed along a line of sight roughly opposite to where the shell initially detonates. None of the existing models could quantitatively explain all the peculiarities observed in SN 2022joj. The low flux ratio of [Ni II] $\lambda$7378 to [Fe II] $\lambda$7155 emission in the late-time nebular spectra indicates a low yield of stable Ni isotopes, favoring a sub-Chandrasekhar mass progenitor. The significant blueshift measured in the [Fe II] $\lambda$7155 line is also consistent with an asymmetric chemical distribution in the ejecta, as is predicted in double-detonation models.Comment: 24 pages, 11 figures, 6 tables. Submitted to Ap